{"format":{"id":"adc","name":"Antibody-drug conjugates","blurb":"A carrier that finds the cell, a linker that lets go at the right moment, and a payload that does the killing; the drug-to-antibody ratio says how many payloads ride along. Peptide and bicyclic conjugates and protein-toxin fusions are here too, since they swap the carrier and keep the idea.","route":"/modalities/adc/","engine":"/pipeline/engine/adc/"},"counts":{"drugs":93,"approved":20,"phase3":43,"trials":305,"companies":58,"papers":44,"ideas":54,"eras":19},"how":{"paragraphs":["An antibody-drug conjugate is an antibody that homes to a protein on the tumour cell, is swallowed, and releases a chemotherapy payload inside it. That widens chemotherapy's safe dose window about a hundredfold, which is why payloads too toxic to give alone can be used, though lung inflammation, neutropenia and eye toxicity from the payload still occur.","Antigen binding → receptor-mediated endocytosis → lysosomal degradation or linker cleavage → payload release → tumour cell death and, with permeable payloads, killing of neighbouring antigen-negative cells."],"from":[{"id":"adc","kind":"technology","name":"Antibody-drug conjugate (ADC)","route":"/technologies/adc/"}],"technologies":[{"id":"adc","kind":"technology","name":"Antibody-drug conjugate (ADC)","route":"/technologies/adc/","status":"approved","tldr":"An antibody-drug conjugate is an antibody that homes to a protein on the tumour cell, is swallowed, and releases a chemotherapy payload inside it. That widens chemotherapy's safe dose window about a hundredfold, which is why payloads too toxic to give alone can be used, though lung inflammation, neutropenia and eye toxicity from the payload still occur."},{"id":"bispecific-adc","kind":"technology","name":"Bispecific ADC","route":"/technologies/bispecific-adc/","status":"phase-3","tldr":"A bispecific ADC is an ADC whose antibody grabs two different proteins on the cancer cell, so it sticks better to tumour and less to healthy tissue."},{"id":"site-specific-conjugation","kind":"technology","name":"Site-specific conjugation & linker chemistry","route":"/technologies/site-specific-conjugation/","status":"established","tldr":"Site-specific conjugation and linker chemistry decide exactly where and how many payloads attach to the antibody, which determines how safe and effective an ADC is."},{"id":"topoisomerase-inhibitors","kind":"technology","name":"Topoisomerase-I inhibitors (and ADC payloads)","route":"/technologies/topoisomerase-inhibitors/","status":"standard-of-care","tldr":"Topoisomerase-I inhibitors jam the enzyme that untangles DNA during copying, causing double-strand breaks. As free drugs (irinotecan, topotecan) they are modest, but their analogues SN-38 and deruxtecan are the dominant antibody-drug conjugate payload class of the 2020s, active after taxane failure; cross-resistance between these ADCs is a growing problem."},{"id":"peptide-drug-conjugate","kind":"technology","name":"Peptide-drug & small-molecule-drug conjugates","route":"/technologies/peptide-drug-conjugate/","status":"approved","tldr":"Like an ADC but with a small targeting peptide instead of an antibody, so it penetrates tumours faster and is cheaper to make."},{"id":"dual-payload-adc","kind":"technology","name":"Dual-payload ADC","route":"/technologies/dual-payload-adc/","status":"phase-1","tldr":"A dual-payload ADC is an ADC carrying two different poisons at once, so the tumour cannot escape by becoming resistant to one."},{"id":"masked-adc","kind":"technology","name":"Masked / conditionally active ADC","route":"/technologies/masked-adc/","status":"phase-2","tldr":"An ADC wearing a mask that only comes off inside the tumour, so it ignores the same protein on healthy tissue."},{"id":"immune-stimulating-adc","kind":"technology","name":"Immune-stimulating antibody conjugate (ISAC)","route":"/technologies/immune-stimulating-adc/","status":"phase-1","tldr":"An immune-stimulating antibody conjugate (ISAC) is an ADC whose payload wakes up the immune system inside the tumour rather than poisoning the cell."},{"id":"degrader-antibody-conjugate","kind":"technology","name":"Degrader-antibody conjugate (DAC)","route":"/technologies/degrader-antibody-conjugate/","status":"phase-1","tldr":"An ADC that delivers a protein-destroying molecule instead of chemotherapy, hitting targets inside the cell that were previously unreachable."},{"id":"antibody-oligonucleotide-conjugates","kind":"technology","name":"Antibody-oligonucleotide conjugates","route":"/technologies/antibody-oligonucleotide-conjugates/","status":"preclinical","tldr":"An ADC that carries a gene-silencing strand instead of a chemotherapy, so it can switch a protein off rather than poison the cell."},{"id":"adc-payload-neutralizer","kind":"technology","name":"ADC payload neutralisers","route":"/technologies/adc-payload-neutralizer/","status":"phase-1","tldr":"An ADC payload neutraliser is an antibody given alongside an ADC that mops up the poison once it leaks into the bloodstream, so the ADC can hit the tumour with fewer side effects."},{"id":"adc-supply-chain","kind":"technology","name":"The ADC supply chain (antibody, payload-linker, conjugation, fill)","route":"/technologies/adc-supply-chain/","status":"established","tldr":"An antibody-drug conjugate needs three separate factories: one growing the antibody, one making the poison and its linker in sealed rooms, and one joining them. Then a fourth fills the vials. Any of the four can hold up the drug."},{"id":"adc-cdmo-manufacturing","kind":"technology","name":"ADC bioconjugation manufacturing (CDMOs)","route":"/technologies/adc-cdmo-manufacturing/","status":"established","tldr":"ADC bioconjugation manufacturing joins a payload so toxic it needs the top containment class (OEB 5) to an antibody, then checks drug-to-antibody ratio and free payload. Capacity sits with a handful of contractors such as Lonza, WuXi XDC and Samsung Biologics, so long queues and China-based exposure shape who can develop ADCs."},{"id":"high-potency-payload-synthesis","kind":"technology","name":"Payload-linker synthesis (high-potency API)","route":"/technologies/high-potency-payload-synthesis/","status":"established","tldr":"Payload-linker synthesis makes the cytotoxic small molecules inside ADCs (exatecan, MMAE, DM1, PBD dimers), whose occupational exposure limits sit in the nanogram range, in facilities built so a speck of dust cannot harm a worker. A handful of licensed sites such as Lonza and WuXi STA supply them, and their lead times gate hundreds of ADCs in development."}]},"terms":[{"id":"payload","kind":"term","name":"Payload (ADC)","route":"/terms/payload/","tldr":"The payload is the poison an ADC carries, usually a chemotherapy far too toxic to give on its own.","category":"ADC chemistry"},{"id":"linker","kind":"term","name":"Linker (ADC)","route":"/terms/linker/","tldr":"The linker is the chemical tether between antibody and payload. It must hold in the blood and let go inside the tumour.","category":"ADC chemistry"},{"id":"dar","kind":"term","name":"Drug-to-antibody ratio (DAR)","route":"/terms/dar/","tldr":"The drug-to-antibody ratio (DAR) is how many payload molecules ride on each antibody, typically 2 to 8.","category":"ADC chemistry"},{"id":"bystander-effect","kind":"term","name":"Bystander effect (ADC)","route":"/terms/bystander-effect/","tldr":"When a released payload leaks out of the targeted cell and kills its neighbours, including cells that lack the target.","category":"ADC chemistry"},{"id":"ild","kind":"term","name":"Interstitial lung disease (ILD) / pneumonitis","route":"/terms/ild/","tldr":"Interstitial lung disease (ILD) is lung inflammation, a serious side effect of some ADCs (especially Enhertu) and immunotherapy.","category":"Side effects"}],"engine":{"route":"/pipeline/engine/adc/","axes":["Target","Payload class"],"rows":32,"cols":6,"counts":{"approved":15,"development":30,"stopped":6,"unclear":0,"untried":155},"placed":79,"total":93,"pct":85},"approved":[{"drug":{"id":"denileukin-diftitox","kind":"drug","name":"Denileukin diftitox","route":"/drugs/denileukin-diftitox/"},"brand":"Lymphir","status":"approved","modality":"IL-2 receptor-directed cytotoxin (fusion protein)","cancers":[],"indications":["Persistent or recurrent CD25-positive CTCL (Ontak; withdrawn 2014)","Relapsed or refractory stage I to III CTCL after at least one systemic therapy (Lymphir)"],"years":[1999,2024],"firstYear":1999,"regions":["US"],"target":{"key":"target","id":"cd25","name":"CD25 (IL-2 receptor alpha)","href":"/targets/cd25/"},"companies":[{"id":"citius-pharmaceuticals","kind":"company","name":"Citius Pharmaceuticals","route":"/companies/citius-pharmaceuticals/"},{"id":"eisai","kind":"company","name":"Eisai","route":"/companies/eisai/"}]},{"drug":{"id":"gemtuzumab-ozogamicin","kind":"drug","name":"Gemtuzumab ozogamicin","route":"/drugs/gemtuzumab-ozogamicin/"},"brand":"Mylotarg","status":"approved","modality":"ADC","cancers":[{"id":"aml","kind":"cancer","name":"Acute myeloid leukaemia","route":"/cancers/aml/"},{"id":"aml-paediatric","kind":"cancer","name":"Acute myeloid leukaemia in children","route":"/cancers/aml-paediatric/"}],"indications":["Relapsed CD33+ AML (withdrawn 2010)","Newly diagnosed and relapsed CD33+ AML"],"years":[2000,2017],"firstYear":2000,"regions":["US"],"target":{"key":"target","id":"cd33","name":"CD33","href":"/targets/cd33/"},"companies":[{"id":"pfizer","kind":"company","name":"Pfizer (incl. Seagen)","route":"/companies/pfizer/"}]},{"drug":{"id":"brentuximab-vedotin","kind":"drug","name":"Brentuximab vedotin","route":"/drugs/brentuximab-vedotin/"},"brand":"Adcetris","status":"approved","modality":"ADC","cancers":[{"id":"hodgkin-lymphoma","kind":"cancer","name":"Hodgkin lymphoma","route":"/cancers/hodgkin-lymphoma/"},{"id":"cutaneous-t-cell-lymphoma","kind":"cancer","name":"Cutaneous T-cell lymphoma (mycosis fungoides and Sezary syndrome)","route":"/cancers/cutaneous-t-cell-lymphoma/"},{"id":"advanced-stage-classical-hodgkin-lymphoma","kind":"cancer","name":"Advanced-stage classical Hodgkin lymphoma (stage III to IV)","route":"/cancers/advanced-stage-classical-hodgkin-lymphoma/"},{"id":"relapsed-refractory-hodgkin-lymphoma","kind":"cancer","name":"Relapsed and refractory classical Hodgkin lymphoma","route":"/cancers/relapsed-refractory-hodgkin-lymphoma/"}],"indications":["Relapsed Hodgkin lymphoma and systemic ALCL","First-line stage III/IV Hodgkin lymphoma with AVD"],"years":[2011,2018],"firstYear":2011,"regions":["US"],"target":{"key":"target","id":"cd30","name":"CD30","href":"/targets/cd30/"},"companies":[{"id":"pfizer","kind":"company","name":"Pfizer (incl. Seagen)","route":"/companies/pfizer/"},{"id":"takeda","kind":"company","name":"Takeda","route":"/companies/takeda/"}]},{"drug":{"id":"trastuzumab-emtansine","kind":"drug","name":"Trastuzumab emtansine","route":"/drugs/trastuzumab-emtansine/"},"brand":"Kadcyla","status":"approved","modality":"ADC","cancers":[{"id":"breast-her2-positive","kind":"cancer","name":"HER2-positive breast cancer","route":"/cancers/breast-her2-positive/"},{"id":"her2-positive-early-breast-cancer","kind":"cancer","name":"Early HER2-positive breast cancer","route":"/cancers/her2-positive-early-breast-cancer/"}],"indications":["HER2+ metastatic breast cancer after trastuzumab and taxane","Adjuvant HER2+ breast cancer with residual disease after neoadjuvant therapy"],"years":[2013,2019],"firstYear":2013,"regions":["US"],"target":{"key":"target","id":"her2","name":"HER2","href":"/targets/her2/"},"companies":[{"id":"roche-genentech","kind":"company","name":"Roche / Genentech","route":"/companies/roche-genentech/"}]},{"drug":{"id":"inotuzumab-ozogamicin","kind":"drug","name":"Inotuzumab ozogamicin","route":"/drugs/inotuzumab-ozogamicin/"},"brand":"Besponsa","status":"approved","modality":"ADC","cancers":[{"id":"all-leukemia","kind":"cancer","name":"Acute lymphoblastic leukaemia","route":"/cancers/all-leukemia/"},{"id":"all-paediatric-relapsed","kind":"cancer","name":"Relapsed and refractory acute lymphoblastic leukaemia in children","route":"/cancers/all-paediatric-relapsed/"},{"id":"all-paediatric-high-risk","kind":"cancer","name":"High-risk acute lymphoblastic leukaemia in children (high-risk B-ALL and T-ALL)","route":"/cancers/all-paediatric-high-risk/"}],"indications":["Relapsed/refractory CD22+ B-ALL, adults","Paediatric patients ≥1 year with relapsed/refractory CD22+ B-ALL"],"years":[2017,2024],"firstYear":2017,"regions":["US"],"target":{"key":"target","id":"cd22","name":"CD22","href":"/targets/cd22/"},"companies":[{"id":"pfizer","kind":"company","name":"Pfizer (incl. Seagen)","route":"/companies/pfizer/"}]},{"drug":{"id":"moxetumomab-pasudotox","kind":"drug","name":"Moxetumomab pasudotox","route":"/drugs/moxetumomab-pasudotox/"},"brand":"Lumoxiti","status":"withdrawn","modality":"Anti-CD22 immunotoxin (Pseudomonas exotoxin A fragment)","cancers":[{"id":"hairy-cell-leukemia","kind":"cancer","name":"Hairy cell leukaemia","route":"/cancers/hairy-cell-leukemia/"}],"indications":["Relapsed/refractory hairy cell leukaemia after ≥2 systemic therapies including a purine analogue"],"years":[2018],"firstYear":2018,"regions":["US"],"target":{"key":"target","id":"cd22","name":"CD22","href":"/targets/cd22/"},"companies":[{"id":"astrazeneca","kind":"company","name":"AstraZeneca","route":"/companies/astrazeneca/"}]},{"drug":{"id":"enfortumab-vedotin","kind":"drug","name":"Enfortumab vedotin","route":"/drugs/enfortumab-vedotin/"},"brand":"Padcev","status":"approved","modality":"ADC","cancers":[{"id":"urothelial","kind":"cancer","name":"Bladder & urothelial cancer","route":"/cancers/urothelial/"},{"id":"muscle-invasive-bladder-cancer","kind":"cancer","name":"Muscle-invasive and advanced bladder cancer","route":"/cancers/muscle-invasive-bladder-cancer/"}],"indications":["Advanced urothelial cancer after platinum and PD-1/PD-L1 (accelerated)","First-line advanced urothelial cancer with pembrolizumab","mUC after platinum + PD-1; 1L with pembrolizumab 2024"],"years":[2019,2022,2023],"firstYear":2019,"regions":["US","EU"],"target":{"key":"target","id":"nectin4","name":"Nectin-4","href":"/targets/nectin4/"},"companies":[{"id":"astellas","kind":"company","name":"Astellas","route":"/companies/astellas/"},{"id":"generate-biomedicines","kind":"company","name":"Generate:Biomedicines","route":"/companies/generate-biomedicines/"},{"id":"pfizer","kind":"company","name":"Pfizer (incl. Seagen)","route":"/companies/pfizer/"}]},{"drug":{"id":"polatuzumab-vedotin","kind":"drug","name":"Polatuzumab vedotin","route":"/drugs/polatuzumab-vedotin/"},"brand":"Polivy","status":"approved","modality":"ADC","cancers":[{"id":"dlbcl","kind":"cancer","name":"Diffuse large B-cell lymphoma","route":"/cancers/dlbcl/"}],"indications":["Relapsed/refractory DLBCL with bendamustine-rituximab after ≥2 lines (accelerated)","Untreated DLBCL, IPI ≥2, with R-CHP (Pola-R-CHP)"],"years":[2019,2023],"firstYear":2019,"regions":["US"],"target":{"key":"target","id":"cd79b","name":"CD79b","href":"/targets/cd79b/"},"companies":[{"id":"chugai","kind":"company","name":"Chugai Pharmaceutical","route":"/companies/chugai/"},{"id":"roche-genentech","kind":"company","name":"Roche / Genentech","route":"/companies/roche-genentech/"}]},{"drug":{"id":"trastuzumab-deruxtecan","kind":"drug","name":"Trastuzumab deruxtecan","route":"/drugs/trastuzumab-deruxtecan/"},"brand":"Enhertu","status":"approved","modality":"ADC","cancers":[{"id":"breast-her2-positive","kind":"cancer","name":"HER2-positive breast cancer","route":"/cancers/breast-her2-positive/"},{"id":"breast-hr-positive","kind":"cancer","name":"HR-positive / HER2-negative breast cancer","route":"/cancers/breast-hr-positive/"},{"id":"gastric","kind":"cancer","name":"Gastric & gastro-oesophageal junction cancer","route":"/cancers/gastric/"},{"id":"gastric-her2-positive","kind":"cancer","name":"HER2-positive gastric cancer","route":"/cancers/gastric-her2-positive/"},{"id":"nsclc","kind":"cancer","name":"Non-small-cell lung cancer","route":"/cancers/nsclc/"},{"id":"colorectal","kind":"cancer","name":"Colorectal cancer","route":"/cancers/colorectal/"},{"id":"oesophageal-adenocarcinoma","kind":"cancer","name":"Oesophageal and junctional adenocarcinoma","route":"/cancers/oesophageal-adenocarcinoma/"},{"id":"salivary-duct-carcinoma","kind":"cancer","name":"Salivary duct carcinoma","route":"/cancers/salivary-duct-carcinoma/"},{"id":"her2-amplified-colorectal","kind":"cancer","name":"HER2-amplified colorectal cancer","route":"/cancers/her2-amplified-colorectal/"},{"id":"her2-low-metastatic-breast-cancer","kind":"cancer","name":"HER2-low and HER2-ultralow metastatic breast cancer","route":"/cancers/her2-low-metastatic-breast-cancer/"},{"id":"her2-positive-early-breast-cancer","kind":"cancer","name":"Early HER2-positive breast cancer","route":"/cancers/her2-positive-early-breast-cancer/"},{"id":"her2-positive-breast-brain-metastases","kind":"cancer","name":"HER2-positive breast cancer with brain metastases","route":"/cancers/her2-positive-breast-brain-metastases/"},{"id":"her2-mutant-nsclc","kind":"cancer","name":"HER2-mutant non-small-cell lung cancer","route":"/cancers/her2-mutant-nsclc/"},{"id":"advanced-small-bowel-adenocarcinoma","kind":"cancer","name":"Advanced and metastatic small bowel adenocarcinoma","route":"/cancers/advanced-small-bowel-adenocarcinoma/"},{"id":"tnbc","kind":"cancer","name":"Triple-negative breast cancer (TNBC)","route":"/cancers/tnbc/"},{"id":"tnbc-metastatic","kind":"cancer","name":"Metastatic triple-negative breast cancer","route":"/cancers/tnbc-metastatic/"},{"id":"gallbladder","kind":"cancer","name":"Gallbladder cancer","route":"/cancers/gallbladder/"},{"id":"biliary-tract-cancer","kind":"cancer","name":"Biliary tract cancer (all types)","route":"/cancers/biliary-tract-cancer/"}],"indications":["HER2+ metastatic breast cancer, ≥2 prior anti-HER2 regimens","HER2-low metastatic breast cancer; HER2-mutant NSCLC","HER2 IHC3+ solid tumours (tumour-agnostic)","HER2-low/ultralow HR+ breast cancer after endocrine therapy (DESTINY-Breast06)","Early-stage HER2+ breast cancer (neoadjuvant and post-neoadjuvant)","Unresectable or metastatic HER2-low breast cancer after chemotherapy in the metastatic setting or recurrence within 6 months of adjuvant chemotherapy (DESTINY-Breast04), hormone-receptor-negative disease included","HER2-low metastatic or unresectable breast cancer after chemotherapy: NICE TA992 (25 July 2024) does not recommend trastuzumab deruxtecan, the cost per quality-adjusted life year being above the range NICE accepts; a rapid review (GID-TA12551) is in development"],"years":[2019,2022,2023,2024,2025,2026],"firstYear":2019,"regions":["US","EU","UK"],"target":{"key":"target","id":"her2","name":"HER2","href":"/targets/her2/"},"companies":[{"id":"astrazeneca","kind":"company","name":"AstraZeneca","route":"/companies/astrazeneca/"},{"id":"daiichi-sankyo","kind":"company","name":"Daiichi Sankyo","route":"/companies/daiichi-sankyo/"},{"id":"gi-innovation","kind":"company","name":"GI Innovation","route":"/companies/gi-innovation/"}]},{"drug":{"id":"belantamab-mafodotin","kind":"drug","name":"Belantamab mafodotin","route":"/drugs/belantamab-mafodotin/"},"brand":"Blenrep","status":"approved","modality":"ADC","cancers":[{"id":"multiple-myeloma","kind":"cancer","name":"Multiple myeloma","route":"/cancers/multiple-myeloma/"},{"id":"myeloma-relapsed-refractory","kind":"cancer","name":"Relapsed or refractory multiple myeloma","route":"/cancers/myeloma-relapsed-refractory/"}],"indications":["Relapsed myeloma ≥4 lines (accelerated; withdrawn 2022)","Relapsed/refractory myeloma after ≥1 prior line, in combination","R/R myeloma with BorDex or PomDex; 23 Jul 2025"],"years":[2020,2025],"firstYear":2020,"regions":["US","EU"],"target":{"key":"target","id":"bcma","name":"BCMA","href":"/targets/bcma/"},"companies":[{"id":"gsk","kind":"company","name":"GSK","route":"/companies/gsk/"}]},{"drug":{"id":"sacituzumab-govitecan","kind":"drug","name":"Sacituzumab govitecan","route":"/drugs/sacituzumab-govitecan/"},"brand":"Trodelvy","status":"approved","modality":"ADC","cancers":[{"id":"tnbc","kind":"cancer","name":"Triple-negative breast cancer (TNBC)","route":"/cancers/tnbc/"},{"id":"breast-hr-positive","kind":"cancer","name":"HR-positive / HER2-negative breast cancer","route":"/cancers/breast-hr-positive/"},{"id":"urothelial","kind":"cancer","name":"Bladder & urothelial cancer","route":"/cancers/urothelial/"},{"id":"tnbc-metastatic","kind":"cancer","name":"Metastatic triple-negative breast cancer","route":"/cancers/tnbc-metastatic/"}],"indications":["Metastatic TNBC, ≥2 prior lines (accelerated; full 2021)","HR+/HER2- metastatic breast cancer after endocrine therapy and ≥2 chemotherapies","First-line metastatic TNBC: monotherapy (PD-1 ineligible) or with pembrolizumab (PD-L1 CPS ≥10)","mTNBC ≥2 lines; HR+ 2023","Unresectable or metastatic TNBC after two or more systemic therapies, at least one for advanced disease (ASCENT); marketing authorisation issued 22 November 2021","First-line unresectable locally advanced or metastatic TNBC in patients who are not candidates for PD-1 or PD-L1 inhibitor therapy (ASCENT-03); listed in the EMA therapeutic indications read on 24 September 2026","Unresectable triple-negative locally advanced or metastatic breast cancer after two or more systemic therapies, at least one for advanced disease; NICE TA819 (17 August 2022) recommends within the marketing authorisation with a commercial arrangement"],"years":[2020,2021,2022,2023,2026],"firstYear":2020,"regions":["US","EU","UK"],"target":{"key":"target","id":"trop2","name":"TROP2","href":"/targets/trop2/"},"companies":[{"id":"gilead","kind":"company","name":"Gilead Sciences (incl. Kite)","route":"/companies/gilead/"}]},{"drug":{"id":"disitamab-vedotin","kind":"drug","name":"Disitamab vedotin","route":"/drugs/disitamab-vedotin/"},"status":"approved","modality":"ADC","cancers":[{"id":"gastric","kind":"cancer","name":"Gastric & gastro-oesophageal junction cancer","route":"/cancers/gastric/"},{"id":"urothelial","kind":"cancer","name":"Bladder & urothelial cancer","route":"/cancers/urothelial/"}],"indications":["HER2+ gastric cancer; HER2-expressing urothelial cancer"],"years":[2021],"firstYear":2021,"regions":["China"],"target":{"key":"target","id":"her2","name":"HER2","href":"/targets/her2/"},"companies":[{"id":"pfizer","kind":"company","name":"Pfizer (incl. Seagen)","route":"/companies/pfizer/"},{"id":"remegen","kind":"company","name":"RemeGen","route":"/companies/remegen/"}]},{"drug":{"id":"zynlonta","kind":"drug","name":"Loncastuximab tesirine","route":"/drugs/zynlonta/"},"brand":"Zynlonta","status":"approved","modality":"ADC","cancers":[{"id":"dlbcl","kind":"cancer","name":"Diffuse large B-cell lymphoma","route":"/cancers/dlbcl/"}],"indications":["Relapsed/refractory DLBCL after ≥2 systemic therapies","R/R DLBCL ≥2 lines (conditional)"],"years":[2021,2022],"firstYear":2021,"regions":["US","EU"],"target":{"key":"target","id":"cd19","name":"CD19","href":"/targets/cd19/"},"companies":[{"id":"adc-therapeutics","kind":"company","name":"ADC Therapeutics","route":"/companies/adc-therapeutics/"}]},{"drug":{"id":"tisotumab-vedotin","kind":"drug","name":"Tisotumab vedotin","route":"/drugs/tisotumab-vedotin/"},"brand":"Tivdak","status":"approved","modality":"ADC","cancers":[{"id":"cervical","kind":"cancer","name":"Cervical cancer","route":"/cancers/cervical/"},{"id":"recurrent-metastatic-cervical-cancer","kind":"cancer","name":"Recurrent or metastatic cervical cancer","route":"/cancers/recurrent-metastatic-cervical-cancer/"}],"indications":["Recurrent/metastatic cervical cancer after chemotherapy (full 2024)","Recurrent/metastatic cervical after systemic therapy; 28 Mar 2025"],"years":[2021,2025],"firstYear":2021,"regions":["US","EU"],"target":{"key":"target","id":"tissue-factor","name":"Tissue factor","href":"/targets/tissue-factor/"},"companies":[{"id":"genmab","kind":"company","name":"Genmab","route":"/companies/genmab/"},{"id":"pfizer","kind":"company","name":"Pfizer (incl. 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bispecifics","route":"/resistance/#bcma-directed-bcma-antigen-loss-biallelic-tnfrsf17-deletion-extracellular-mutations"},{"name":"T-cell exhaustion and low fitness","category":"immune-evasion","categoryLabel":"Immune evasion","how":"Prior lines, high tumour burden, and continuous bispecific dosing exhaust T cells; CAR-T products from heavily pretreated patients expand poorly.","route":"/resistance/#bcma-directed-t-cell-exhaustion-and-low-fitness"},{"name":"Soluble BCMA decoy","category":"pharmacology","categoryLabel":"Pharmacology","how":"Shed BCMA binds drug in circulation.","route":"/resistance/#bcma-directed-soluble-bcma-decoy"}],"sources":[{"label":"CARTITUDE-4 (NEJM 2023)","url":"https://www.nejm.org/doi/full/10.1056/NEJMoa2303379"}]}],"papers":[{"id":"paper-tropion-breast02-ann-oncol-2026","kind":"paper","name":"Datopotamab deruxtecan in patients with untreated, advanced triple-negative breast cancer (TROPION-Breast02): a randomised, open-label, international, phase III trial","route":"/key-papers/paper-tropion-breast02-ann-oncol-2026/","year":2026,"journal":"Annals of Oncology","paperType":"rct","tldr":"The trial of 644 women with newly metastatic triple-negative breast cancer who could not have immunotherapy, in which the antibody-drug conjugate datopotamab deruxtecan held the cancer still for 10.8 months against 5.6 with chemotherapy and lengthened life from 18.7 to 23.7 months.","via":[{"id":"datopotamab-deruxtecan","kind":"drug","name":"Datopotamab deruxtecan","route":"/drugs/datopotamab-deruxtecan/"},{"id":"adc","kind":"technology","name":"Antibody-drug conjugate (ADC)","route":"/technologies/adc/"},{"id":"topoisomerase-inhibitors","kind":"technology","name":"Topoisomerase-I inhibitors (and ADC payloads)","route":"/technologies/topoisomerase-inhibitors/"}]},{"id":"paper-oh-destiny-pantumor02-biliary-pancreatic-esmo-open-2026","kind":"paper","name":"Efficacy and safety of trastuzumab deruxtecan in patients with HER2-expressing biliary tract or pancreatic tumors: a subgroup analysis of DESTINY-PanTumor02","route":"/key-papers/paper-oh-destiny-pantumor02-biliary-pancreatic-esmo-open-2026/","year":2026,"journal":"ESMO Open","paperType":"observational","tldr":"In the tumour-agnostic trial that led to the HER2 IHC 3+ approval, trastuzumab deruxtecan shrank about a quarter of 41 pretreated biliary cancers overall and more than half of those with the strongest HER2 stain, while pancreatic tumours barely responded.","via":[{"id":"trastuzumab-deruxtecan","kind":"drug","name":"Trastuzumab deruxtecan","route":"/drugs/trastuzumab-deruxtecan/"}]},{"id":"paper-boissiere-michot-her2-ultralow-tnbc-virchows-arch-2026","kind":"paper","name":"Exploring the spectrum of HER2 in non-metastatic triple negative breast cancer: from HER2-null to HER2-low, including HER2-ultralow status","route":"/key-papers/paper-boissiere-michot-her2-ultralow-tnbc-virchows-arch-2026/","year":2026,"journal":"Virchows Archiv","paperType":"observational","tldr":"Reclassifying 367 chemotherapy-naive triple-negative cancers put 38% in HER2-null, 38% in HER2-ultralow and 24% in HER2-low; the categories differed a little in size, grade and BRCA1 methylation but not in relapse over ten years.","via":[{"id":"trastuzumab-deruxtecan","kind":"drug","name":"Trastuzumab deruxtecan","route":"/drugs/trastuzumab-deruxtecan/"}]},{"id":"paper-tropion-breast01-china-cohort-esmo-open-2026","kind":"paper","name":"TROPION-Breast01 China cohort: datopotamab deruxtecan versus chemotherapy in previously treated HR-positive, HER2-negative breast cancer","route":"/key-papers/paper-tropion-breast01-china-cohort-esmo-open-2026/","year":2026,"journal":"ESMO Open","paperType":"rct","tldr":"Among the 83 patients enrolled in mainland China, datopotamab deruxtecan roughly doubled the time before the cancer grew compared with chemotherapy, with fewer severe side effects, in line with the global trial.","via":[{"id":"datopotamab-deruxtecan","kind":"drug","name":"Datopotamab deruxtecan","route":"/drugs/datopotamab-deruxtecan/"}]},{"id":"paper-mondaca-erbb2-gallbladder-us-chile-jco-go-2024","kind":"paper","name":"Clinical and genomic characterization of ERBB2-altered gallbladder cancer: exploring differences between an American and a Chilean cohort","route":"/key-papers/paper-mondaca-erbb2-gallbladder-us-chile-jco-go-2024/","year":2024,"journal":"JCO Global Oncology","paperType":"observational","tldr":"In 260 gallbladder cancer patients from New York and Santiago, HER2 gene changes were found in about one in seven at both centres, split between extra copies and point mutations, and patients with them lived longer.","via":[{"id":"trastuzumab-deruxtecan","kind":"drug","name":"Trastuzumab deruxtecan","route":"/drugs/trastuzumab-deruxtecan/"}]},{"id":"paper-destiny-breast06-nejm-2024","kind":"paper","name":"DESTINY-Breast06: trastuzumab deruxtecan before any chemotherapy in hormone-receptor-positive, HER2-low or ultralow breast cancer","route":"/key-papers/paper-destiny-breast06-nejm-2024/","year":2024,"journal":"New England Journal of Medicine","paperType":"rct","tldr":"Given as the first chemotherapy-type treatment after hormone therapy stopped working, trastuzumab deruxtecan delayed progression by about five months compared with standard chemotherapy, including in tumours with barely detectable HER2.","via":[{"id":"trastuzumab-deruxtecan","kind":"drug","name":"Trastuzumab deruxtecan","route":"/drugs/trastuzumab-deruxtecan/"},{"id":"adc","kind":"technology","name":"Antibody-drug conjugate (ADC)","route":"/technologies/adc/"}]},{"id":"paper-destiny-pantumor02-jco-2024","kind":"paper","name":"DESTINY-PanTumor02: trastuzumab deruxtecan in HER2-expressing solid tumours","route":"/key-papers/paper-destiny-pantumor02-jco-2024/","year":2024,"journal":"Journal of Clinical Oncology","paperType":"observational","tldr":"Across seven tumour types including endometrial, cervical and ovarian cancers, trastuzumab deruxtecan shrank tumours in about 37 percent of patients overall and 61 percent of those with the highest HER2 expression, leading to a tumour-agnostic approval.","via":[{"id":"trastuzumab-deruxtecan","kind":"drug","name":"Trastuzumab deruxtecan","route":"/drugs/trastuzumab-deruxtecan/"}]},{"id":"paper-ev-302-nejm-2024","kind":"paper","name":"EV-302: enfortumab vedotin plus pembrolizumab replaces chemotherapy as first treatment for advanced bladder cancer","route":"/key-papers/paper-ev-302-nejm-2024/","year":2024,"journal":"New England Journal of Medicine","paperType":"rct","tldr":"Combining the Nectin-4 antibody-drug conjugate enfortumab vedotin with pembrolizumab nearly doubled survival compared with platinum chemotherapy in advanced urothelial cancer, the biggest advance in this disease in 40 years.","via":[{"id":"enfortumab-vedotin","kind":"drug","name":"Enfortumab vedotin","route":"/drugs/enfortumab-vedotin/"},{"id":"adc","kind":"technology","name":"Antibody-drug conjugate (ADC)","route":"/technologies/adc/"}]},{"id":"paper-ghsg-hd21-brecadd-vs-ebeacopp-advanced-hodgkin-lancet-2024","kind":"paper","name":"GHSG HD21: PET-guided BrECADD versus escalated BEACOPP in advanced-stage classical Hodgkin lymphoma","route":"/key-papers/paper-ghsg-hd21-brecadd-vs-ebeacopp-advanced-hodgkin-lancet-2024/","year":2024,"journal":"The Lancet","paperType":"rct","tldr":"A new regimen built around brentuximab vedotin cured more patients with advanced Hodgkin lymphoma than the intensive BEACOPP standard, and did so with less toxicity, including less damage to fertility.","via":[{"id":"brentuximab-vedotin","kind":"drug","name":"Brentuximab vedotin","route":"/drugs/brentuximab-vedotin/"}]},{"id":"paper-innovatv-301-tisotumab-nejm-2024","kind":"paper","name":"innovaTV 301: tisotumab vedotin versus chemotherapy as second- or third-line therapy for recurrent cervical cancer","route":"/key-papers/paper-innovatv-301-tisotumab-nejm-2024/","year":2024,"journal":"New England Journal of Medicine","paperType":"rct","tldr":"The tissue factor-directed antibody-drug conjugate tisotumab vedotin lengthened survival compared with chemotherapy in cervical cancer that had progressed after first-line treatment, at the cost of eye and nerve side effects.","via":[{"id":"tisotumab-vedotin","kind":"drug","name":"Tisotumab vedotin","route":"/drugs/tisotumab-vedotin/"}]},{"id":"paper-swog-s1826-nivolumab-avd-nejm-2024","kind":"paper","name":"SWOG S1826: nivolumab plus AVD chemotherapy versus brentuximab-AVD for advanced Hodgkin lymphoma in adolescents and adults","route":"/key-papers/paper-swog-s1826-nivolumab-avd-nejm-2024/","year":2024,"journal":"New England Journal of Medicine","paperType":"rct","tldr":"Adding a PD-1 antibody to chemotherapy beat the brentuximab-based standard, with 92% of patients progression-free at two years and less nerve damage.","via":[{"id":"brentuximab-vedotin","kind":"drug","name":"Brentuximab vedotin","route":"/drugs/brentuximab-vedotin/"}]},{"id":"paper-ohba-herb-trastuzumab-deruxtecan-biliary-jco-2024","kind":"paper","name":"Trastuzumab deruxtecan in human epidermal growth factor receptor 2-expressing biliary tract cancer (HERB; NCCH1805): a multicenter, single-arm, phase II trial","route":"/key-papers/paper-ohba-herb-trastuzumab-deruxtecan-biliary-jco-2024/","year":2024,"journal":"Journal of Clinical Oncology","paperType":"observational","tldr":"The antibody-drug conjugate trastuzumab deruxtecan shrank tumours in about a third of Japanese patients with HER2-positive bile duct or gallbladder cancer after chemotherapy, and in one in eight with low HER2, but a quarter developed lung inflammation and two died of it.","via":[{"id":"trastuzumab-deruxtecan","kind":"drug","name":"Trastuzumab deruxtecan","route":"/drugs/trastuzumab-deruxtecan/"}]},{"id":"paper-tropion-breast01-jco-2024","kind":"paper","name":"TROPION-Breast01: datopotamab deruxtecan versus chemotherapy in pretreated hormone-receptor-positive breast cancer, and why a PFS win did not translate to survival","route":"/key-papers/paper-tropion-breast01-jco-2024/","year":2024,"journal":"Journal of Clinical Oncology","paperType":"rct","tldr":"The TROP2-directed antibody-drug conjugate Dato-DXd delayed progression by about two months compared with chemotherapy, but patients did not live longer, which stalled its approval in breast cancer.","via":[{"id":"datopotamab-deruxtecan","kind":"drug","name":"Datopotamab deruxtecan","route":"/drugs/datopotamab-deruxtecan/"},{"id":"adc","kind":"technology","name":"Antibody-drug conjugate (ADC)","route":"/technologies/adc/"},{"id":"topoisomerase-inhibitors","kind":"technology","name":"Topoisomerase-I inhibitors (and ADC payloads)","route":"/technologies/topoisomerase-inhibitors/"}]},{"id":"paper-destiny-lung02-goto-jco-2023","kind":"paper","name":"DESTINY-Lung02: two doses of trastuzumab deruxtecan in HER2-mutant metastatic non-small-cell lung cancer","route":"/key-papers/paper-destiny-lung02-goto-jco-2023/","year":2023,"journal":"Journal of Clinical Oncology","paperType":"rct","tldr":"Comparing two doses of trastuzumab deruxtecan in HER2-mutant lung cancer showed that the lower 5.4 mg/kg dose gave the same response rate of about half with far less lung toxicity, fixing the approved dose.","via":[{"id":"trastuzumab-deruxtecan","kind":"drug","name":"Trastuzumab deruxtecan","route":"/drugs/trastuzumab-deruxtecan/"}]},{"id":"paper-mirasol-nejm-2023","kind":"paper","name":"MIRASOL: mirvetuximab soravtansine versus chemotherapy in folate receptor alpha-high platinum-resistant ovarian cancer","route":"/key-papers/paper-mirasol-nejm-2023/","year":2023,"journal":"New England Journal of Medicine","paperType":"rct","tldr":"The antibody-drug conjugate mirvetuximab soravtansine lengthened survival compared with chemotherapy in platinum-resistant ovarian cancer with high folate receptor alpha expression, the first drug ever to do so in this setting.","via":[{"id":"mirvetuximab-soravtansine","kind":"drug","name":"Mirvetuximab soravtansine","route":"/drugs/mirvetuximab-soravtansine/"}]},{"id":"paper-napoli-3-lancet-2023","kind":"paper","name":"NAPOLI-3: NALIRIFOX versus gemcitabine plus nab-paclitaxel as first treatment for metastatic pancreatic cancer","route":"/key-papers/paper-napoli-3-lancet-2023/","year":2023,"journal":"The Lancet","paperType":"rct","tldr":"NAPOLI-3 randomised 770 patients with untreated metastatic pancreatic cancer to NALIRIFOX, a four-drug regimen built on liposomal irinotecan, or to gemcitabine plus nab-paclitaxel, the doublet most patients receive. NALIRIFOX lengthened life and delayed progression, the first positive first-line trial in a decade, though conventional FOLFIRINOX remains the usual choice where affordable.","via":[{"id":"topoisomerase-inhibitors","kind":"technology","name":"Topoisomerase-I inhibitors (and ADC payloads)","route":"/technologies/topoisomerase-inhibitors/"}]},{"id":"paper-ahod1331-brentuximab-vedotin-paediatric-hodgkin-castellino-nejm-2022","kind":"paper","name":"AHOD1331: brentuximab vedotin with chemotherapy in paediatric high-risk Hodgkin lymphoma","route":"/key-papers/paper-ahod1331-brentuximab-vedotin-paediatric-hodgkin-castellino-nejm-2022/","year":2022,"journal":"New England Journal of Medicine","paperType":"rct","tldr":"Swapping bleomycin for the antibody-drug conjugate brentuximab vedotin in children's chemotherapy for advanced Hodgkin lymphoma cut the risk of relapse or death by 59 percent with no extra toxicity.","via":[{"id":"brentuximab-vedotin","kind":"drug","name":"Brentuximab vedotin","route":"/drugs/brentuximab-vedotin/"}]},{"id":"paper-kindler-lancet-oncol","kind":"paper","name":"Anetumab ravtansine versus vinorelbine in patients with relapsed, mesothelin-positive malignant pleural mesothelioma (ARCS-M): a randomised, open-label phase 2 trial","route":"/key-papers/paper-kindler-lancet-oncol/","year":2022,"journal":"The Lancet Oncology","paperType":"rct","tldr":"Paper cited by one trial page, one treatment page and one idea page, indexed on Europe PMC as PubMed record 35358455 and published in The Lancet Oncology; the citing pages link this DOI, which is how the record was matched.","via":[{"id":"anetumab-ravtansine","kind":"drug","name":"Anetumab ravtansine","route":"/drugs/anetumab-ravtansine/"}]},{"id":"paper-destiny-breast03-nejm-2022","kind":"paper","name":"DESTINY-Breast03: trastuzumab deruxtecan beats T-DM1 as second-line treatment of HER2-positive metastatic breast cancer","route":"/key-papers/paper-destiny-breast03-nejm-2022/","year":2022,"journal":"New England Journal of Medicine","paperType":"rct","tldr":"A newer antibody-drug conjugate, trastuzumab deruxtecan, kept HER2-positive metastatic breast cancer under control roughly four times longer than the previous standard, T-DM1, and later lengthened survival.","via":[{"id":"trastuzumab-deruxtecan","kind":"drug","name":"Trastuzumab deruxtecan","route":"/drugs/trastuzumab-deruxtecan/"},{"id":"trastuzumab-emtansine","kind":"drug","name":"Trastuzumab emtansine","route":"/drugs/trastuzumab-emtansine/"},{"id":"adc","kind":"technology","name":"Antibody-drug conjugate (ADC)","route":"/technologies/adc/"},{"id":"topoisomerase-inhibitors","kind":"technology","name":"Topoisomerase-I inhibitors (and ADC payloads)","route":"/technologies/topoisomerase-inhibitors/"}]},{"id":"paper-destiny-breast04-nejm-2022","kind":"paper","name":"DESTINY-Breast04: trastuzumab deruxtecan works in HER2-low breast cancer, creating a new treatable group","route":"/key-papers/paper-destiny-breast04-nejm-2022/","year":2022,"journal":"New England Journal of Medicine","paperType":"rct","tldr":"Breast cancers with only a little HER2 on their surface, long called HER2-negative, responded to trastuzumab deruxtecan and patients lived about six months longer than on chemotherapy. It created the HER2-low category.","via":[{"id":"trastuzumab-deruxtecan","kind":"drug","name":"Trastuzumab deruxtecan","route":"/drugs/trastuzumab-deruxtecan/"},{"id":"adc","kind":"technology","name":"Antibody-drug conjugate (ADC)","route":"/technologies/adc/"}]},{"id":"paper-destiny-lung01-nejm-2022","kind":"paper","name":"DESTINY-Lung01: trastuzumab deruxtecan in HER2-mutant non-small-cell lung cancer","route":"/key-papers/paper-destiny-lung01-nejm-2022/","year":2022,"journal":"New England Journal of Medicine","paperType":"observational","tldr":"Trastuzumab deruxtecan shrank tumours in more than half of patients with previously treated HER2-mutant lung cancer, a driver with no approved therapy until this study, though lung inflammation was a serious side effect.","via":[{"id":"trastuzumab-deruxtecan","kind":"drug","name":"Trastuzumab deruxtecan","route":"/drugs/trastuzumab-deruxtecan/"}]},{"id":"paper-keynote-355-nejm-2022","kind":"paper","name":"KEYNOTE-355: pembrolizumab plus chemotherapy for PD-L1-positive advanced triple-negative breast cancer","route":"/key-papers/paper-keynote-355-nejm-2022/","year":2022,"journal":"New England Journal of Medicine","paperType":"rct","tldr":"Adding pembrolizumab to first-line chemotherapy lengthened survival by almost seven months in advanced triple-negative breast cancer whose tumours had a PD-L1 combined positive score of 10 or more.","via":[{"id":"sacituzumab-govitecan","kind":"drug","name":"Sacituzumab govitecan","route":"/drugs/sacituzumab-govitecan/"}]},{"id":"paper-polarix-polatuzumab-rchp-nejm-2022","kind":"paper","name":"POLARIX: swapping vincristine for the antibody-drug conjugate polatuzumab vedotin in first-line treatment of diffuse large B-cell lymphoma","route":"/key-papers/paper-polarix-polatuzumab-rchp-nejm-2022/","year":2022,"journal":"New England Journal of Medicine","paperType":"rct","tldr":"Replacing one chemotherapy drug in R-CHOP with a CD79b antibody-drug conjugate modestly reduced progression (2-year PFS 76.7% versus 70.2%) without changing survival or side effects.","via":[{"id":"polatuzumab-vedotin","kind":"drug","name":"Polatuzumab vedotin","route":"/drugs/polatuzumab-vedotin/"},{"id":"adc","kind":"technology","name":"Antibody-drug conjugate (ADC)","route":"/technologies/adc/"}]},{"id":"paper-tuxedo-1-trastuzumab-deruxtecan-brain-metastases-nat-med-2022","kind":"paper","name":"TUXEDO-1: trastuzumab deruxtecan in HER2-positive breast cancer with active brain metastases","route":"/key-papers/paper-tuxedo-1-trastuzumab-deruxtecan-brain-metastases-nat-med-2022/","year":2022,"journal":"Nature Medicine","paperType":"observational","tldr":"In a small trial, the antibody-drug conjugate trastuzumab deruxtecan shrank brain metastases in almost three quarters of women with HER2-positive breast cancer, showing that a large antibody-based drug can work inside the brain.","via":[{"id":"trastuzumab-deruxtecan","kind":"drug","name":"Trastuzumab deruxtecan","route":"/drugs/trastuzumab-deruxtecan/"}]},{"id":"paper-yamazaki-nat-commun","kind":"paper","name":"Antibody-drug conjugates with dual payloads for combating breast tumor heterogeneity and drug resistance","route":"/key-papers/paper-yamazaki-nat-commun/","year":2021,"journal":"Nature Communications","paperType":"basic","tldr":"Paper cited by one technology page and one idea page, indexed on Europe PMC as PubMed record 34112795 and published in Nature Communications; the citing pages link this DOI, which is how the record was matched.","via":[{"id":"dual-payload-adc","kind":"technology","name":"Dual-payload ADC","route":"/technologies/dual-payload-adc/"}]},{"id":"paper-ascent-nejm-2021","kind":"paper","name":"ASCENT: sacituzumab govitecan doubles survival in heavily pretreated metastatic triple-negative breast cancer","route":"/key-papers/paper-ascent-nejm-2021/","year":2021,"journal":"New England Journal of Medicine","paperType":"rct","tldr":"In triple-negative breast cancer that had already been through at least two treatments, the TROP2 antibody-drug conjugate sacituzumab govitecan roughly doubled the time patients lived compared with standard chemotherapy.","via":[{"id":"sacituzumab-govitecan","kind":"drug","name":"Sacituzumab govitecan","route":"/drugs/sacituzumab-govitecan/"},{"id":"adc","kind":"technology","name":"Antibody-drug conjugate (ADC)","route":"/technologies/adc/"},{"id":"topoisomerase-inhibitors","kind":"technology","name":"Topoisomerase-I inhibitors (and ADC payloads)","route":"/technologies/topoisomerase-inhibitors/"}]},{"id":"paper-bardia-ascent-trop2-biomarker-ann-oncol-2021","kind":"paper","name":"Biomarker analyses in the phase III ASCENT study of sacituzumab govitecan versus chemotherapy in patients with metastatic triple-negative breast cancer","route":"/key-papers/paper-bardia-ascent-trop2-biomarker-ann-oncol-2021/","year":2021,"journal":"Annals of Oncology","paperType":"rct","tldr":"In ASCENT, sacituzumab govitecan beat chemotherapy in tumours with high and medium TROP2 protein, and worked whether or not the patient carried a germline BRCA mutation; the low-TROP2 group was too small to judge.","via":[{"id":"sacituzumab-govitecan","kind":"drug","name":"Sacituzumab govitecan","route":"/drugs/sacituzumab-govitecan/"}]},{"id":"paper-schettini-her2-low-pam50-npj-breast-cancer-2021","kind":"paper","name":"Clinical, pathological, and PAM50 gene expression features of HER2-low breast cancer","route":"/key-papers/paper-schettini-her2-low-pam50-npj-breast-cancer-2021/","year":2021,"journal":"npj Breast Cancer","paperType":"observational","tldr":"Among 3,689 HER2-negative breast cancers, 37% of triple-negative and 65% of hormone receptor-positive tumours were HER2-low; in triple-negative disease HER2-low tumours were biologically indistinguishable from HER2-0 and pathologists agreed poorly on the call.","via":[{"id":"trastuzumab-deruxtecan","kind":"drug","name":"Trastuzumab deruxtecan","route":"/drugs/trastuzumab-deruxtecan/"}]},{"id":"paper-schettini-her2-low-features-npj-breast-cancer-2021","kind":"paper","name":"Clinical, pathological, and PAM50 gene expression features of HER2-low breast cancer","route":"/key-papers/paper-schettini-her2-low-features-npj-breast-cancer-2021/","year":2021,"journal":"NPJ Breast Cancer","paperType":"observational","tldr":"A 3,689-patient study showing that 36.6 percent of triple-negative tumours are HER2-low, that in triple-negative disease HER2-low tumours are biologically no different from HER2-zero ones, and that pathologists agree poorly on the score; the label matters only because a drug now depends on it.","via":[{"id":"trastuzumab-deruxtecan","kind":"drug","name":"Trastuzumab deruxtecan","route":"/drugs/trastuzumab-deruxtecan/"}]},{"id":"paper-destiny-crc01-lancet-oncol-2021","kind":"paper","name":"DESTINY-CRC01: trastuzumab deruxtecan in HER2-expressing metastatic colorectal cancer","route":"/key-papers/paper-destiny-crc01-lancet-oncol-2021/","year":2021,"journal":"The Lancet Oncology","paperType":"observational","tldr":"Trastuzumab deruxtecan shrank tumours in about 45 percent of patients with HER2-high colorectal cancer, including those who had already received other HER2 drugs, but did nothing for tumours with low HER2 expression and carried a risk of lung inflammation.","via":[{"id":"trastuzumab-deruxtecan","kind":"drug","name":"Trastuzumab deruxtecan","route":"/drugs/trastuzumab-deruxtecan/"}]},{"id":"paper-ackerman-nat-cancer","kind":"paper","name":"Immune-stimulating antibody conjugates elicit robust myeloid activation and durable antitumor immunity","route":"/key-papers/paper-ackerman-nat-cancer/","year":2021,"journal":"Nature Cancer","paperType":"basic","tldr":"Paper cited by one technology page, indexed on Europe PMC as PubMed record 35121890 and published in Nature Cancer; the citing page links this DOI, which is how the record was matched.","via":[{"id":"immune-stimulating-adc","kind":"technology","name":"Immune-stimulating antibody conjugate (ISAC)","route":"/technologies/immune-stimulating-adc/"}]},{"id":"paper-keynote-204-pembrolizumab-vs-brentuximab-rr-hodgkin-lancet-oncol-2021","kind":"paper","name":"KEYNOTE-204: pembrolizumab versus brentuximab vedotin in relapsed or refractory classical Hodgkin lymphoma","route":"/key-papers/paper-keynote-204-pembrolizumab-vs-brentuximab-rr-hodgkin-lancet-oncol-2021/","year":2021,"journal":"The Lancet Oncology","paperType":"rct","tldr":"In a head-to-head trial, the PD-1 antibody pembrolizumab kept relapsed Hodgkin lymphoma at bay for longer than brentuximab vedotin, making immunotherapy the preferred choice after transplant failure or for patients who cannot have a transplant.","via":[{"id":"brentuximab-vedotin","kind":"drug","name":"Brentuximab vedotin","route":"/drugs/brentuximab-vedotin/"}]},{"id":"paper-cooper-chem-soc-rev","kind":"paper","name":"Peptides as a platform for targeted therapeutics for cancer: peptide-drug conjugates (PDCs)","route":"/key-papers/paper-cooper-chem-soc-rev/","year":2021,"journal":"Chemical Society reviews","paperType":"review","tldr":"Paper cited by one technology page, indexed on Europe PMC as PubMed record 33346298 and published in Chemical Society reviews; the citing page links this DOI, which is how the record was matched.","via":[{"id":"peptide-drug-conjugate","kind":"technology","name":"Peptide-drug & small-molecule-drug conjugates","route":"/technologies/peptide-drug-conjugate/"}]},{"id":"paper-destiny-gastric01-nejm-2020","kind":"paper","name":"DESTINY-Gastric01: trastuzumab deruxtecan in previously treated HER2-positive gastric cancer","route":"/key-papers/paper-destiny-gastric01-nejm-2020/","year":2020,"journal":"New England Journal of Medicine","paperType":"rct","tldr":"Trastuzumab deruxtecan shrank tumours in half of patients with HER2-positive gastric cancer that had progressed after trastuzumab, 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Let a validated algorithm do the counting.","via":[{"id":"trastuzumab-deruxtecan","kind":"drug","name":"Trastuzumab deruxtecan","route":"/drugs/trastuzumab-deruxtecan/"}]},{"id":"idea-adc-for-mesothelioma","kind":"idea","name":"Antibody-drug conjugates for mesothelioma: why they have failed so far and how they could work","route":"/ideas/idea-adc-for-mesothelioma/","maturity":"early-clinical","tldr":"Nearly every mesothelioma carries the surface protein mesothelin, yet the one antibody-drug conjugate tried in a randomised trial did no better than chemotherapy. The idea is to fix the three reasons it failed rather than abandon the approach.","via":[{"id":"anetumab-ravtansine","kind":"drug","name":"Anetumab ravtansine","route":"/drugs/anetumab-ravtansine/"},{"id":"trastuzumab-deruxtecan","kind":"drug","name":"Trastuzumab deruxtecan","route":"/drugs/trastuzumab-deruxtecan/"},{"id":"adc","kind":"technology","name":"Antibody-drug conjugate (ADC)","route":"/technologies/adc/"}]},{"id":"idea-bladder-preservation-mibc","kind":"idea","name":"Bladder preservation for MIBC after perioperative EV + pembrolizumab complete response","route":"/ideas/idea-bladder-preservation-mibc/","maturity":"early-clinical","tldr":"If the ADC-immunotherapy combination erases the tumour in more than half of patients before surgery, some may not need their bladder removed at all.","via":[{"id":"enfortumab-vedotin","kind":"drug","name":"Enfortumab vedotin","route":"/drugs/enfortumab-vedotin/"}]},{"id":"idea-tr1-brain-mets-default-included","kind":"idea","name":"Brain metastases included by default in every solid-tumour trial","route":"/ideas/idea-tr1-brain-mets-default-included/","maturity":"early-clinical","tldr":"Up to a fifth of people with advanced solid tumours have cancer in the brain and are usually barred from trials. Letting in those whose brain disease is treated, stable or symptom-free would widen trials and tell us whether drugs work in the brain.","via":[{"id":"trastuzumab-deruxtecan","kind":"drug","name":"Trastuzumab deruxtecan","route":"/drugs/trastuzumab-deruxtecan/"}]},{"id":"idea-tr2-her2-low-reference-materials","kind":"idea","name":"Calibrated reference slides so every lab scores HER2-low the same way","route":"/ideas/idea-tr2-her2-low-reference-materials/","maturity":"early-clinical","tldr":"Whether a breast cancer counts as HER2-low, and so qualifies for trastuzumab deruxtecan, turns on the least reproducible step of the HER2 stain, score 1+ versus 0. Cell-line microarrays with a known quantity of HER2 protein per cell, run alongside clinical slides, would anchor every laboratory to a physical standard.","via":[{"id":"trastuzumab-deruxtecan","kind":"drug","name":"Trastuzumab deruxtecan","route":"/drugs/trastuzumab-deruxtecan/"}]},{"id":"idea-tdxd-first-then-nothing","kind":"idea","name":"Can T-DXd alone cure early HER2-positive disease?","route":"/ideas/idea-tdxd-first-then-nothing/","maturity":"early-clinical","tldr":"If Enhertu produces complete responses in two-thirds of patients before surgery, a trial should test whether some need no chemotherapy, antibodies, or even radiation afterwards.","via":[{"id":"trastuzumab-deruxtecan","kind":"drug","name":"Trastuzumab deruxtecan","route":"/drugs/trastuzumab-deruxtecan/"}]},{"id":"idea-chemo-free-hodgkin","kind":"idea","name":"Chemotherapy-free Hodgkin lymphoma: brentuximab + PD-1 in early stage","route":"/ideas/idea-chemo-free-hodgkin/","maturity":"early-clinical","tldr":"For a cancer already cured in 90% of young people, the goal is curing without the chemotherapy and radiation that cause heart disease and second cancers decades later.","via":[{"id":"brentuximab-vedotin","kind":"drug","name":"Brentuximab vedotin","route":"/drugs/brentuximab-vedotin/"},{"id":"adc","kind":"technology","name":"Antibody-drug conjugate (ADC)","route":"/technologies/adc/"}]},{"id":"idea-tnbc-ctdna-guided-adjuvant-decisions","kind":"idea","name":"ctDNA-guided adjuvant decisions after residual disease: escalate the positive, spare the negative","route":"/ideas/idea-tnbc-ctdna-guided-adjuvant-decisions/","maturity":"early-clinical","tldr":"After pre-surgery chemotherapy leaves tumour behind, a blood test for tumour DNA triples the risk of distant relapse when positive. The one trial that acted on it found the DNA usually appeared too late. A trial that tests at surgery with a tumour-informed assay, escalates positives to an antibody-drug conjugate and observes negatives has not been run.","via":[{"id":"datopotamab-deruxtecan","kind":"drug","name":"Datopotamab deruxtecan","route":"/drugs/datopotamab-deruxtecan/"},{"id":"sacituzumab-govitecan","kind":"drug","name":"Sacituzumab govitecan","route":"/drugs/sacituzumab-govitecan/"},{"id":"adc","kind":"technology","name":"Antibody-drug conjugate (ADC)","route":"/technologies/adc/"}]},{"id":"idea-ctdna-guided-dlbcl-frontline","kind":"idea","name":"ctDNA-guided escalation and de-escalation in frontline DLBCL","route":"/ideas/idea-ctdna-guided-dlbcl-frontline/","maturity":"early-clinical","tldr":"Use an ultra-sensitive blood test after two cycles to decide who needs more than R-CHOP and who can stop early.","via":[{"id":"polatuzumab-vedotin","kind":"drug","name":"Polatuzumab vedotin","route":"/drugs/polatuzumab-vedotin/"}]},{"id":"idea-ctdna-escalation-tnbc","kind":"idea","name":"ctDNA-triggered escalation in early TNBC","route":"/ideas/idea-ctdna-escalation-tnbc/","maturity":"early-clinical","tldr":"Instead of treating everyone after surgery, test blood every few months and treat only when tumour DNA reappears.","via":[{"id":"adc","kind":"technology","name":"Antibody-drug conjugate (ADC)","route":"/technologies/adc/"}]},{"id":"idea-tr1-adc-dose-and-schedule-optimisation","kind":"idea","name":"Dose and schedule optimisation trials specific to antibody-drug conjugates","route":"/ideas/idea-tr1-adc-dose-and-schedule-optimisation/","maturity":"early-clinical","tldr":"Antibody-drug conjugates deliver chemotherapy payloads into tumours but cause lung, eye and nerve damage that tracks total exposure, and several were approved without an optimised dose. Randomised comparisons of lower doses, longer intervals and capped cumulative payload could keep the benefit while cutting these harms.","via":[{"id":"enfortumab-vedotin","kind":"drug","name":"Enfortumab vedotin","route":"/drugs/enfortumab-vedotin/"},{"id":"mirvetuximab-soravtansine","kind":"drug","name":"Mirvetuximab soravtansine","route":"/drugs/mirvetuximab-soravtansine/"},{"id":"sacituzumab-govitecan","kind":"drug","name":"Sacituzumab govitecan","route":"/drugs/sacituzumab-govitecan/"},{"id":"trastuzumab-deruxtecan","kind":"drug","name":"Trastuzumab deruxtecan","route":"/drugs/trastuzumab-deruxtecan/"}]},{"id":"idea-tr2-combo-dose-matrix","kind":"idea","name":"Find the lowest effective doses of both drugs in a combination, not the highest tolerated","route":"/ideas/idea-tr2-combo-dose-matrix/","maturity":"early-clinical","tldr":"Combination trials usually keep one drug at full dose and push the other as high as patients can bear. Testing a grid of dose pairs would find combinations that work at lower, safer doses.","via":[{"id":"adc","kind":"technology","name":"Antibody-drug conjugate (ADC)","route":"/technologies/adc/"}]},{"id":"idea-her2-adc-serous-endometrial","kind":"idea","name":"HER2 ADCs as standard for HER2-positive serous endometrial cancer","route":"/ideas/idea-her2-adc-serous-endometrial/","maturity":"early-clinical","tldr":"Serous endometrial cancers often overproduce HER2. Enhertu already works in them; testing HER2 in every p53-abnormal tumour and using the ADC earlier could change outcomes for the worst subtype.","via":[{"id":"trastuzumab-deruxtecan","kind":"drug","name":"Trastuzumab deruxtecan","route":"/drugs/trastuzumab-deruxtecan/"}]},{"id":"idea-neoadjuvant-adc-io","kind":"idea","name":"Neoadjuvant ADC + IO replacing anthracycline chemotherapy in TNBC","route":"/ideas/idea-neoadjuvant-adc-io/","maturity":"early-clinical","tldr":"Replace the toughest part of pre-surgery chemotherapy with an ADC plus immunotherapy, aiming for the same cure rate with less harm.","via":[{"id":"datopotamab-deruxtecan","kind":"drug","name":"Datopotamab deruxtecan","route":"/drugs/datopotamab-deruxtecan/"},{"id":"sacituzumab-govitecan","kind":"drug","name":"Sacituzumab govitecan","route":"/drugs/sacituzumab-govitecan/"},{"id":"adc","kind":"technology","name":"Antibody-drug conjugate (ADC)","route":"/technologies/adc/"}]},{"id":"idea-reg-adc-platform-designation","kind":"idea","name":"Platform designation for ADC linker-payloads so manufacturing data carry across","route":"/ideas/idea-reg-adc-platform-designation/","maturity":"early-clinical","tldr":"Antibody-drug conjugates built on the same linker and payload, such as deruxtecan or vedotin, share the same conjugation process, payload synthesis, impurity profile and much of the toxicology. FDA, EMA and PMDA should designate these linker-payloads as platforms so a new ADC files only antibody-specific manufacturing and toxicology data.","via":[{"id":"adc","kind":"technology","name":"Antibody-drug conjugate (ADC)","route":"/technologies/adc/"},{"id":"site-specific-conjugation","kind":"technology","name":"Site-specific conjugation & linker chemistry","route":"/technologies/site-specific-conjugation/"}]},{"id":"idea-tr2-biomarker-negative-arms","kind":"idea","name":"Randomised trials to test whether biomarker-negative patients really do not benefit","route":"/ideas/idea-tr2-biomarker-negative-arms/","maturity":"early-clinical","tldr":"Patients are denied a drug when a test says they will not benefit, but that restriction is usually inferred from enrichment trials rather than tested. For high-stakes markers with weak evidence in the negative group, such as PD-L1 and HER2 0, randomised trials in biomarker-negative patients should test the assumption itself.","via":[{"id":"trastuzumab-deruxtecan","kind":"drug","name":"Trastuzumab deruxtecan","route":"/drugs/trastuzumab-deruxtecan/"}]},{"id":"idea-tr1-response-adapted-dose-reduction","kind":"idea","name":"Reduce the dose once the cancer responds: response-adapted de-escalation trials","route":"/ideas/idea-tr1-response-adapted-dose-reduction/","maturity":"early-clinical","tldr":"The dose needed to shrink a tumour may be higher than the dose needed to keep it from growing back. Trials that lower the dose once a response is achieved could reduce long-term side effects without losing control.","via":[{"id":"trastuzumab-deruxtecan","kind":"drug","name":"Trastuzumab deruxtecan","route":"/drugs/trastuzumab-deruxtecan/"},{"id":"adc","kind":"technology","name":"Antibody-drug conjugate (ADC)","route":"/technologies/adc/"}]},{"id":"idea-gbc-reflex-her2-testing-advanced-biliary","kind":"idea","name":"Reflex HER2 testing of every advanced gallbladder and extrahepatic biliary cancer","route":"/ideas/idea-gbc-reflex-her2-testing-advanced-biliary/","maturity":"early-clinical","tldr":"Between one in eleven and one in five gallbladder cancers is HER2-positive and two HER2 drugs are now approved, but testing still happens only when someone asks. Making it automatic on every advanced biliary diagnosis, on resection tissue where it exists, would find the patients the trials were built for.","via":[{"id":"trastuzumab-deruxtecan","kind":"drug","name":"Trastuzumab deruxtecan","route":"/drugs/trastuzumab-deruxtecan/"}]},{"id":"idea-tnbc-her2-ultralow-testing-uptake","kind":"idea","name":"Reflex re-scoring of HER2 0 versus 1+ with digital assistance so every eligible triple-negative patient reaches trastuzumab deruxtecan","route":"/ideas/idea-tnbc-her2-ultralow-testing-uptake/","maturity":"early-clinical","tldr":"About a third of triple-negative tumours are HER2-low and so eligible for trastuzumab deruxtecan, but the difference between a HER2 score of 0 and 1+ is the one pathologists agree on least, and most triple-negative tumours were scored before the label mattered. Re-scoring archived slides with digital help when a patient relapses would find the eligible third.","via":[{"id":"trastuzumab-deruxtecan","kind":"drug","name":"Trastuzumab deruxtecan","route":"/drugs/trastuzumab-deruxtecan/"},{"id":"adc","kind":"technology","name":"Antibody-drug conjugate (ADC)","route":"/technologies/adc/"}]},{"id":"idea-tr1-model-based-dose-finding-with-late-toxicity","kind":"idea","name":"Retire the 3+3: model-based dose finding that counts late and chronic side effects","route":"/ideas/idea-tr1-model-based-dose-finding-with-late-toxicity/","maturity":"early-clinical","tldr":"The traditional way of finding a dose looks only at severe side effects in the first month. Modern statistical designs can use all patients' data and count the grumbling, long-lasting problems that make people quit months later.","via":[{"id":"adc","kind":"technology","name":"Antibody-drug conjugate (ADC)","route":"/technologies/adc/"}]},{"id":"idea-cns-first-adc-strategy","kind":"idea","name":"Systemic-first management of HER2-positive brain metastases","route":"/ideas/idea-cns-first-adc-strategy/","maturity":"early-clinical","tldr":"With Enhertu and tucatinib controlling brain metastases in most patients, radiation could be reserved for those who do not respond, sparing cognitive side effects.","via":[{"id":"trastuzumab-deruxtecan","kind":"drug","name":"Trastuzumab deruxtecan","route":"/drugs/trastuzumab-deruxtecan/"}]},{"id":"idea-tr1-weight-based-vs-flat-dosing-trials","kind":"idea","name":"Test flat versus weight-based dosing of antibodies, and use dose banding to cut waste","route":"/ideas/idea-tr1-weight-based-vs-flat-dosing-trials/","maturity":"early-clinical","tldr":"Monoclonal antibodies and ADCs have moved from weight-based to flat dosing on modelling alone, which is convenient but gives lighter patients relatively more drug. Randomised or pharmacokinetic comparisons, plus rounding doses to vial sizes where exposure is equivalent, could keep effectiveness while cutting cost and waste.","via":[{"id":"trastuzumab-deruxtecan","kind":"drug","name":"Trastuzumab deruxtecan","route":"/drugs/trastuzumab-deruxtecan/"},{"id":"adc","kind":"technology","name":"Antibody-drug conjugate (ADC)","route":"/technologies/adc/"}]},{"id":"idea-tnbc-brain-metastasis-trials","kind":"idea","name":"Trials that include, and report, brain metastases in triple-negative breast cancer","route":"/ideas/idea-tnbc-brain-metastasis-trials/","maturity":"early-clinical","tldr":"Nearly half of women with metastatic triple-negative breast cancer develop brain metastases and survive under five months after the diagnosis, yet the trials that set the standard mostly exclude active brain disease. Requiring a brain metastasis cohort in every phase 3, with intracranial response as an endpoint, would answer whether the new drugs reach the brain.","via":[{"id":"datopotamab-deruxtecan","kind":"drug","name":"Datopotamab deruxtecan","route":"/drugs/datopotamab-deruxtecan/"},{"id":"sacituzumab-govitecan","kind":"drug","name":"Sacituzumab govitecan","route":"/drugs/sacituzumab-govitecan/"},{"id":"trastuzumab-deruxtecan","kind":"drug","name":"Trastuzumab deruxtecan","route":"/drugs/trastuzumab-deruxtecan/"},{"id":"adc","kind":"technology","name":"Antibody-drug conjugate (ADC)","route":"/technologies/adc/"}]},{"id":"idea-trop2-pet-selection","kind":"idea","name":"TROP2 PET to choose and sequence TROP2 ADCs","route":"/ideas/idea-trop2-pet-selection/","maturity":"early-clinical","tldr":"Use a whole-body TROP2 scan instead of a single tissue stain to decide which patients get a TROP2 ADC, which one, and when to switch.","via":[{"id":"datopotamab-deruxtecan","kind":"drug","name":"Datopotamab deruxtecan","route":"/drugs/datopotamab-deruxtecan/"},{"id":"sacituzumab-govitecan","kind":"drug","name":"Sacituzumab govitecan","route":"/drugs/sacituzumab-govitecan/"},{"id":"sacituzumab-tirumotecan","kind":"drug","name":"Sacituzumab tirumotecan","route":"/drugs/sacituzumab-tirumotecan/"},{"id":"adc","kind":"technology","name":"Antibody-drug conjugate (ADC)","route":"/technologies/adc/"}]},{"id":"idea-bio2-tumour-anchored-tgfbeta-trap","kind":"idea","name":"Anchor a TGF-beta trap in the tumour stroma so it cannot act everywhere","route":"/ideas/idea-bio2-tumour-anchored-tgfbeta-trap/","maturity":"preclinical-evidence","tldr":"TGF-beta is a signal that keeps immune cells out of tumours, but blocking it throughout the body caused bleeding and heart toxicity and sank bintrafusp alfa. Tethering the blocker to tumour stroma with a FAP anchor, a collagen-binding domain or a protease-activated mask could give the benefit without the harm.","via":[{"id":"masked-adc","kind":"technology","name":"Masked / conditionally active ADC","route":"/technologies/masked-adc/"}]},{"id":"idea-bio1-stromal-resistance-blockade","kind":"idea","name":"Block the survival signals the tumour's neighbours provide","route":"/ideas/idea-bio1-stromal-resistance-blockade/","maturity":"preclinical-evidence","tldr":"Cancer cells can survive a drug because surrounding normal cells feed them growth signals. Blocking those signals could make existing drugs work better and longer.","via":[{"id":"patritumab-deruxtecan","kind":"drug","name":"Patritumab deruxtecan","route":"/drugs/patritumab-deruxtecan/"}]},{"id":"idea-bio2-antigen-presentation-triage","kind":"idea","name":"Check whether a tumour can still show itself to the immune system","route":"/ideas/idea-bio2-antigen-presentation-triage/","maturity":"preclinical-evidence","tldr":"Some tumours have broken the machinery that displays their identity to immune cells. Those patients cannot benefit from most immunotherapy and should be routed elsewhere.","via":[{"id":"adc","kind":"technology","name":"Antibody-drug conjugate (ADC)","route":"/technologies/adc/"}]},{"id":"idea-tr2-resistance-mechanism-baskets","kind":"idea","name":"Combination baskets defined by resistance mechanism rather than by cancer type","route":"/ideas/idea-tr2-resistance-mechanism-baskets/","maturity":"preclinical-evidence","tldr":"Group patients by why their last drug stopped working, then test the combination designed to fix that specific failure, whatever the cancer.","via":[{"id":"adc","kind":"technology","name":"Antibody-drug conjugate (ADC)","route":"/technologies/adc/"}]},{"id":"idea-reg-hpapi-continuous-flow","kind":"idea","name":"Continuous-flow synthesis of ultra-potent ADC payloads to ease the capacity squeeze","route":"/ideas/idea-reg-hpapi-continuous-flow/","maturity":"preclinical-evidence","tldr":"The poisons carried by antibody-drug conjugates are so toxic that only a few factories can make them, and they are booked years ahead. Making them in small continuous reactors would ease the bottleneck.","via":[{"id":"enfortumab-vedotin","kind":"drug","name":"Enfortumab vedotin","route":"/drugs/enfortumab-vedotin/"},{"id":"trastuzumab-deruxtecan","kind":"drug","name":"Trastuzumab deruxtecan","route":"/drugs/trastuzumab-deruxtecan/"},{"id":"adc","kind":"technology","name":"Antibody-drug conjugate (ADC)","route":"/technologies/adc/"}]},{"id":"idea-efflux-agnostic","kind":"idea","name":"Efflux-agnostic therapy for mesenchymal TNBC","route":"/ideas/idea-efflux-agnostic/","maturity":"preclinical-evidence","tldr":"Some tumours pump out every drug. Use treatments the pumps cannot touch: radiation, radioligands, immune cells, and payloads designed to evade them.","via":[{"id":"sacituzumab-tirumotecan","kind":"drug","name":"Sacituzumab tirumotecan","route":"/drugs/sacituzumab-tirumotecan/"},{"id":"adc","kind":"technology","name":"Antibody-drug conjugate (ADC)","route":"/technologies/adc/"},{"id":"degrader-antibody-conjugate","kind":"technology","name":"Degrader-antibody conjugate (DAC)","route":"/technologies/degrader-antibody-conjugate/"}]},{"id":"idea-bio2-cxcr4-mobilise-then-kill","kind":"idea","name":"Flush dormant cells out of bone marrow, then kill them","route":"/ideas/idea-bio2-cxcr4-mobilise-then-kill/","maturity":"preclinical-evidence","tldr":"Sleeping cancer cells hide in bone marrow where drugs cannot reach them. Pushing them into the bloodstream on purpose, then treating, might clear them.","via":[{"id":"adc","kind":"technology","name":"Antibody-drug conjugate (ADC)","route":"/technologies/adc/"}]},{"id":"idea-fus-plus-adc-glioma","kind":"idea","name":"Focused-ultrasound BBB opening to deliver ADCs and radioligands to glioma","route":"/ideas/idea-fus-plus-adc-glioma/","maturity":"preclinical-evidence","tldr":"Brain tumours have targets that ADCs could hit, but antibodies cannot cross the barrier. Open the barrier with ultrasound first.","via":[{"id":"adc","kind":"technology","name":"Antibody-drug conjugate (ADC)","route":"/technologies/adc/"}]},{"id":"idea-bio1-multi-organ-chip-tox","kind":"idea","name":"Linked human organ chips to predict side effects before people are dosed","route":"/ideas/idea-bio1-multi-organ-chip-tox/","maturity":"preclinical-evidence","tldr":"Damage to the lungs, heart or liver is a common reason cancer drugs fail. Connected chips of human tissue may spot this earlier than animal tests.","via":[{"id":"adc","kind":"technology","name":"Antibody-drug conjugate (ADC)","route":"/technologies/adc/"}]},{"id":"idea-organoid-guided-adc","kind":"idea","name":"Patient-derived organoids to pick ADC payloads","route":"/ideas/idea-organoid-guided-adc/","maturity":"preclinical-evidence","tldr":"Grow the patient's tumour in a dish and test which ADC payload kills it before choosing among three TROP2 ADCs.","via":[{"id":"datopotamab-deruxtecan","kind":"drug","name":"Datopotamab deruxtecan","route":"/drugs/datopotamab-deruxtecan/"},{"id":"sacituzumab-govitecan","kind":"drug","name":"Sacituzumab govitecan","route":"/drugs/sacituzumab-govitecan/"},{"id":"adc","kind":"technology","name":"Antibody-drug conjugate (ADC)","route":"/technologies/adc/"}]},{"id":"idea-payload-switching","kind":"idea","name":"Payload-class switching as the rule for ADC sequencing","route":"/ideas/idea-payload-switching/","maturity":"preclinical-evidence","tldr":"When one ADC fails, the next should carry a different kind of poison, not just aim at a different protein.","via":[{"id":"adc","kind":"technology","name":"Antibody-drug conjugate (ADC)","route":"/technologies/adc/"},{"id":"topoisomerase-inhibitors","kind":"technology","name":"Topoisomerase-I inhibitors (and ADC payloads)","route":"/technologies/topoisomerase-inhibitors/"},{"id":"dual-payload-adc","kind":"technology","name":"Dual-payload ADC","route":"/technologies/dual-payload-adc/"}]},{"id":"idea-fra-adc-sequencing-ovarian","kind":"idea","name":"Sequence folate-receptor ADCs by payload class","route":"/ideas/idea-fra-adc-sequencing-ovarian/","maturity":"preclinical-evidence","tldr":"Three FRα ADCs carry different poisons (tubulin, hemiasterlin, topoisomerase). Use them in sequence rather than treating them as interchangeable.","via":[{"id":"luveltamab-tazevibulin","kind":"drug","name":"Luveltamab tazevibulin","route":"/drugs/luveltamab-tazevibulin/"},{"id":"mirvetuximab-soravtansine","kind":"drug","name":"Mirvetuximab soravtansine","route":"/drugs/mirvetuximab-soravtansine/"},{"id":"rinatabart-sesutecan","kind":"drug","name":"Rinatabart sesutecan","route":"/drugs/rinatabart-sesutecan/"}]},{"id":"idea-her2-adc-sequencing-payload","kind":"idea","name":"Sequencing HER2 ADCs by payload after T-DXd","route":"/ideas/idea-her2-adc-sequencing-payload/","maturity":"preclinical-evidence","tldr":"When Enhertu stops working, the next ADC should probably carry a different kind of payload, such as the tubulin inhibitors in Kadcyla or ARX788, rather than another topoisomerase drug.","via":[{"id":"arx788","kind":"drug","name":"ARX788","route":"/drugs/arx788/"},{"id":"disitamab-vedotin","kind":"drug","name":"Disitamab vedotin","route":"/drugs/disitamab-vedotin/"},{"id":"trastuzumab-deruxtecan","kind":"drug","name":"Trastuzumab deruxtecan","route":"/drugs/trastuzumab-deruxtecan/"},{"id":"trastuzumab-emtansine","kind":"drug","name":"Trastuzumab emtansine","route":"/drugs/trastuzumab-emtansine/"}]},{"id":"idea-bio1-tumour-on-chip-penetration","kind":"idea","name":"Tumour-on-a-chip with blood flow to test whether big drugs actually get in","route":"/ideas/idea-bio1-tumour-on-chip-penetration/","maturity":"preclinical-evidence","tldr":"Large drugs such as antibody-drug conjugates must cross vessel walls and travel through dense tissue. A chip with flowing channels and human tissue can measure how far they get.","via":[{"id":"sacituzumab-govitecan","kind":"drug","name":"Sacituzumab govitecan","route":"/drugs/sacituzumab-govitecan/"},{"id":"trastuzumab-deruxtecan","kind":"drug","name":"Trastuzumab deruxtecan","route":"/drugs/trastuzumab-deruxtecan/"},{"id":"adc","kind":"technology","name":"Antibody-drug conjugate (ADC)","route":"/technologies/adc/"}]},{"id":"idea-bio1-dual-antigen-adc-escape","kind":"idea","name":"Two-target antibody drugs to close the antigen escape route","route":"/ideas/idea-bio1-dual-antigen-adc-escape/","maturity":"preclinical-evidence","tldr":"If a drug relies on one marker, the tumour can survive by dropping it. A drug that recognises two markers at once makes that escape harder.","via":[{"id":"izalontamab-brengitecan","kind":"drug","name":"Izalontamab brengitecan","route":"/drugs/izalontamab-brengitecan/"},{"id":"adc","kind":"technology","name":"Antibody-drug conjugate (ADC)","route":"/technologies/adc/"},{"id":"bispecific-adc","kind":"technology","name":"Bispecific ADC","route":"/technologies/bispecific-adc/"}]},{"id":"idea-bio1-antibody-degrader-conjugates","kind":"idea","name":"Use antibodies to deliver protein-destroying drugs into the right cells","route":"/ideas/idea-bio1-antibody-degrader-conjugates/","maturity":"preclinical-evidence","tldr":"Drugs that destroy proteins can hit healthy cells too. Attaching them to an antibody that only docks onto tumour cells would keep them where they are needed.","via":[{"id":"adc","kind":"technology","name":"Antibody-drug conjugate (ADC)","route":"/technologies/adc/"},{"id":"degrader-antibody-conjugate","kind":"technology","name":"Degrader-antibody conjugate (DAC)","route":"/technologies/degrader-antibody-conjugate/"}]},{"id":"idea-bio1-slfn11-payload-guidance","kind":"idea","name":"Use SLFN11 status to decide which antibody-drug payload to give next","route":"/ideas/idea-bio1-slfn11-payload-guidance/","maturity":"preclinical-evidence","tldr":"A single protein predicts whether a tumour will respond to DNA-damaging drug payloads. Measuring it could stop patients receiving a second drug of the same kind that will not work.","via":[{"id":"adc","kind":"technology","name":"Antibody-drug conjugate (ADC)","route":"/technologies/adc/"},{"id":"topoisomerase-inhibitors","kind":"technology","name":"Topoisomerase-I inhibitors (and ADC payloads)","route":"/technologies/topoisomerase-inhibitors/"}]},{"id":"idea-bio2-transferrin-shuttle-adc","kind":"idea","name":"Use the brain's own transport door to carry antibody drugs across","route":"/ideas/idea-bio2-transferrin-shuttle-adc/","maturity":"preclinical-evidence","tldr":"The brain imports iron through the transferrin receptor. Antibody shuttle domains that bind that receptor raise brain exposure roughly ten to fifty-fold in primates and are already used in clinical Alzheimer's antibodies; the same engineering could carry antibody-drug conjugates or T-cell engagers to brain metastases.","via":[{"id":"trastuzumab-deruxtecan","kind":"drug","name":"Trastuzumab deruxtecan","route":"/drugs/trastuzumab-deruxtecan/"},{"id":"adc","kind":"technology","name":"Antibody-drug conjugate (ADC)","route":"/technologies/adc/"}]},{"id":"idea-alpha-after-adc","kind":"idea","name":"Alpha radioligands after ADC failure","route":"/ideas/idea-alpha-after-adc/","maturity":"speculative","tldr":"When ADCs against a surface protein stop working because the payload no longer kills, use the same protein to deliver radiation instead.","via":[{"id":"adc","kind":"technology","name":"Antibody-drug conjugate (ADC)","route":"/technologies/adc/"}]},{"id":"idea-fund-academic-adc-bispecific-platform","kind":"idea","name":"An open engineering platform for academic ADCs and bispecifics","route":"/ideas/idea-fund-academic-adc-bispecific-platform/","maturity":"speculative","tldr":"Academic labs find new tumour targets but cannot turn an antibody into an antibody-drug conjugate or a bispecific without licensed linker and payload technology. A shared platform would provide that at no cost for first trials.","via":[{"id":"adc","kind":"technology","name":"Antibody-drug conjugate (ADC)","route":"/technologies/adc/"},{"id":"site-specific-conjugation","kind":"technology","name":"Site-specific conjugation & linker chemistry","route":"/technologies/site-specific-conjugation/"}]},{"id":"idea-dual-payload-first","kind":"idea","name":"Dual-payload ADCs in first line to prevent resistance","route":"/ideas/idea-dual-payload-first/","maturity":"speculative","tldr":"Rather than waiting for resistance to one payload and then switching, give two mechanisms from day one, as HIV therapy does.","via":[{"id":"adc","kind":"technology","name":"Antibody-drug conjugate (ADC)","route":"/technologies/adc/"},{"id":"site-specific-conjugation","kind":"technology","name":"Site-specific conjugation & linker chemistry","route":"/technologies/site-specific-conjugation/"},{"id":"dual-payload-adc","kind":"technology","name":"Dual-payload ADC","route":"/technologies/dual-payload-adc/"}]},{"id":"idea-tr2-termination-reports","kind":"idea","name":"Public post-mortem reports when a cancer drug programme is stopped","route":"/ideas/idea-tr2-termination-reports/","maturity":"speculative","tldr":"When an aeroplane crashes, an independent report explains why so it does not happen again. When a cancer drug programme is abandoned, nothing is written. Change that.","via":[{"id":"rovalpituzumab-tesirine","kind":"drug","name":"Rovalpituzumab tesirine","route":"/drugs/rovalpituzumab-tesirine/"}]},{"id":"idea-bio1-antigen-mapping-at-progression","kind":"idea","name":"Re-map the tumour's surface proteins before choosing the next antibody drug","route":"/ideas/idea-bio1-antigen-mapping-at-progression/","maturity":"speculative","tldr":"Antibody drugs need their target to still be present. After one fails, checking which surface markers remain would guide the choice of the next one instead of guessing.","via":[{"id":"adc","kind":"technology","name":"Antibody-drug conjugate (ADC)","route":"/technologies/adc/"}]},{"id":"idea-tr1-pk-informed-organ-thresholds","kind":"idea","name":"Replace fixed kidney and liver cut-offs with drug-specific, pharmacology-based thresholds","route":"/ideas/idea-tr1-pk-informed-organ-thresholds/","maturity":"speculative","tldr":"Most trials copy the same kidney and liver cut-offs, such as creatinine clearance above 60, regardless of how the drug is cleared. Setting each threshold from the drug's own clearance route and organ-impairment pharmacokinetic studies would let patients with mild organ impairment join safely instead of being excluded.","via":[{"id":"adc","kind":"technology","name":"Antibody-drug conjugate (ADC)","route":"/technologies/adc/"}]},{"id":"idea-fund-head-to-head-mandate","kind":"idea","name":"Require head-to-head trials against the best in class for later entrants","route":"/ideas/idea-fund-head-to-head-mandate/","maturity":"speculative","tldr":"Once two drugs of a kind exist, a third should have to prove itself against the best of them, not against an outdated comparison, so patients and payers learn which is actually better.","via":[{"id":"datopotamab-deruxtecan","kind":"drug","name":"Datopotamab deruxtecan","route":"/drugs/datopotamab-deruxtecan/"},{"id":"sacituzumab-govitecan","kind":"drug","name":"Sacituzumab 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bioconjugates","url":"https://www.lonza.com/bioconjugates"}},{"id":"piramal-grangemouth","name":"Piramal Pharma Solutions Grangemouth","operator":"Piramal Pharma Solutions","operatorRoute":"/companies/piramal-pharma-solutions/","ownership":"cdmo","city":"Grangemouth","country":"GB","capabilities":["adc-conjugation"],"capabilityLabels":["ADC conjugation"],"drugs":[],"source":{"label":"Piramal Pharma Solutions ADC","url":"https://www.piramalpharmasolutions.com/"}},{"id":"samsung-biologics-songdo-adc","name":"Samsung Biologics ADC facility","operator":"Samsung Biologics","operatorRoute":"/companies/samsung-biologics/","ownership":"cdmo","city":"Incheon (Songdo)","country":"KR","capabilities":["adc-conjugation","antibody-drug-substance"],"capabilityLabels":["ADC conjugation","Antibody drug substance"],"drugs":[],"source":{"label":"Samsung Biologics","url":"https://samsungbiologics.com/"}},{"id":"wuxi-xdc-singapore","name":"WuXi XDC Singapore","operator":"WuXi 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vial.","route":"/manufacturing/#chain-adcs","technologies":[{"id":"adc-supply-chain","kind":"technology","name":"The ADC supply chain (antibody, payload-linker, conjugation, fill)","route":"/technologies/adc-supply-chain/"},{"id":"monoclonal-antibody-manufacturing","kind":"technology","name":"Antibody manufacturing (CHO bioprocessing)","route":"/technologies/monoclonal-antibody-manufacturing/"},{"id":"high-potency-payload-synthesis","kind":"technology","name":"Payload-linker synthesis (high-potency API)","route":"/technologies/high-potency-payload-synthesis/"},{"id":"site-specific-conjugation","kind":"technology","name":"Site-specific conjugation & linker chemistry","route":"/technologies/site-specific-conjugation/"},{"id":"adc-cdmo-manufacturing","kind":"technology","name":"ADC bioconjugation manufacturing (CDMOs)","route":"/technologies/adc-cdmo-manufacturing/"},{"id":"sterile-fill-finish","kind":"technology","name":"Sterile fill-finish and lyophilisation","route":"/technologies/sterile-fill-finish/"}],"companies":[{"id":"daiichi-sankyo","kind":"company","name":"Daiichi Sankyo","route":"/companies/daiichi-sankyo/"},{"id":"astrazeneca","kind":"company","name":"AstraZeneca","route":"/companies/astrazeneca/"},{"id":"pfizer","kind":"company","name":"Pfizer (incl. 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Then a fourth fills the vials. Any of the four can hold up the drug."},{"id":"adc-cdmo-manufacturing","kind":"technology","name":"ADC bioconjugation manufacturing (CDMOs)","route":"/technologies/adc-cdmo-manufacturing/","tldr":"ADC bioconjugation manufacturing joins a payload so toxic it needs the top containment class (OEB 5) to an antibody, then checks drug-to-antibody ratio and free payload. Capacity sits with a handful of contractors such as Lonza, WuXi XDC and Samsung Biologics, so long queues and China-based exposure shape who can develop ADCs."},{"id":"high-potency-payload-synthesis","kind":"technology","name":"Payload-linker synthesis (high-potency API)","route":"/technologies/high-potency-payload-synthesis/","tldr":"Payload-linker synthesis makes the cytotoxic small molecules inside ADCs (exatecan, MMAE, DM1, PBD dimers), whose occupational exposure limits sit in the nanogram range, in facilities built so a speck of dust cannot harm a worker. A handful of licensed sites such as Lonza and WuXi STA supply them, and their lead times gate hundreds of ADCs in development."}]},"drugs":[{"id":"a166","kind":"drug","name":"A166","route":"/drugs/a166/"},{"id":"abbv-706","kind":"drug","name":"ABBV-706","route":"/drugs/abbv-706/"},{"id":"ak146d1","kind":"drug","name":"AK146D1","route":"/drugs/ak146d1/"},{"id":"amt-116","kind":"drug","name":"AMT-116","route":"/drugs/amt-116/"},{"id":"anetumab-ravtansine","kind":"drug","name":"Anetumab ravtansine","route":"/drugs/anetumab-ravtansine/"},{"id":"arx788","kind":"drug","name":"ARX788","route":"/drugs/arx788/"},{"id":"azd4360","kind":"drug","name":"AZD4360","route":"/drugs/azd4360/"},{"id":"azd4512","kind":"drug","name":"AZD4512","route":"/drugs/azd4512/"},{"id":"azd5335","kind":"drug","name":"AZD5335","route":"/drugs/azd5335/"},{"id":"belantamab-mafodotin","kind":"drug","name":"Belantamab 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adizutecan","route":"/drugs/telisotuzumab-adizutecan/"},{"id":"telisotuzumab-vedotin","kind":"drug","name":"Telisotuzumab vedotin","route":"/drugs/telisotuzumab-vedotin/"},{"id":"tilatamig-samrotecan","kind":"drug","name":"Tilatamig samrotecan","route":"/drugs/tilatamig-samrotecan/"},{"id":"tisotumab-vedotin","kind":"drug","name":"Tisotumab vedotin","route":"/drugs/tisotumab-vedotin/"},{"id":"tqb2102","kind":"drug","name":"TQB2102","route":"/drugs/tqb2102/"},{"id":"tqb6411","kind":"drug","name":"TQB6411","route":"/drugs/tqb6411/"},{"id":"trastuzumab-brengitecan","kind":"drug","name":"Trastuzumab brengitecan","route":"/drugs/trastuzumab-brengitecan/"},{"id":"trastuzumab-deruxtecan","kind":"drug","name":"Trastuzumab deruxtecan","route":"/drugs/trastuzumab-deruxtecan/"},{"id":"trastuzumab-duocarmazine","kind":"drug","name":"Trastuzumab duocarmazine","route":"/drugs/trastuzumab-duocarmazine/"},{"id":"trastuzumab-emtansine","kind":"drug","name":"Trastuzumab emtansine","route":"/drugs/trastuzumab-emtansine/"},{"id":"trastuzumab-pamirtecan","kind":"drug","name":"Trastuzumab pamirtecan","route":"/drugs/trastuzumab-pamirtecan/"},{"id":"trastuzumab-rezetecan","kind":"drug","name":"Trastuzumab rezetecan","route":"/drugs/trastuzumab-rezetecan/"},{"id":"tusamitamab-ravtansine","kind":"drug","name":"Tusamitamab ravtansine","route":"/drugs/tusamitamab-ravtansine/"},{"id":"upifitamab-rilsodotin","kind":"drug","name":"Upifitamab rilsodotin","route":"/drugs/upifitamab-rilsodotin/"},{"id":"xnw27011","kind":"drug","name":"XNW27011","route":"/drugs/xnw27011/"},{"id":"yl201","kind":"drug","name":"YL201","route":"/drugs/yl201/"},{"id":"yl202","kind":"drug","name":"YL202","route":"/drugs/yl202/"},{"id":"zanidatamab-zovodotin","kind":"drug","name":"Zanidatamab zovodotin","route":"/drugs/zanidatamab-zovodotin/"},{"id":"zelenectide-pevedotin","kind":"drug","name":"Zelenectide pevedotin","route":"/drugs/zelenectide-pevedotin/"},{"id":"zilovertamab-vedotin","kind":"drug","name":"Zilovertamab vedotin","route":"/drugs/zilovertamab-vedotin/"},{"id":"zl-1310","kind":"drug","name":"ZL-1310","route":"/drugs/zl-1310/"}],"note":"Every section is read from existing corpus records and names them (from, via, exemplars, refs); a section with nothing behind it is empty. Medicines of a format are the open drug engine's (/pipeline/engine/); technologies are listed in src/lib/modular-formats.ts. CC BY-NC 4.0, attribute Data from OnCo (onco.cc). Not medical advice."}