Tumour-agnostic (tissue-agnostic) approval
A tumour-agnostic approval lets a drug be used for any cancer carrying a specific molecular feature, regardless of where it started.
Pembrolizumab (MSI-H 2017; TMB-H 2020), larotrectinib/entrectinib (NTRK), dabrafenib-trametinib (BRAF V600E), selpercatinib (RET), T-DXd (HER2 IHC3+, 2024), repotrectinib (NTRK). Requires basket trials and broad genomic testing.
This paper established a new regulatory paradigm: a drug approved for a molecular feature regardless of organ. It made MSI/MMR testing standard across advanced cancers and remains the clearest example of a biomarker that works across histologies. It also anchored the idea that mutation load, via neoantigens, is what makes tumours visible to T cells.
This small trial explained why colorectal cancer had seemed immune-resistant (most is MMR-proficient) and established the principle that a genomic feature, not the tissue of origin, can predict immunotherapy response. It led directly to the 2017 tissue-agnostic approval of pembrolizumab and to routine MMR/MSI testing of many cancers. Every patient with advanced dMMR cancer should now be considered for checkpoint blockade.
Pages like this
not linked directly; found by shared links- TargetNTRK
Shares Adopt tumour-agnostic cancer drug labels across regions by reliance, not re-review, Reciprocal recognition of tumour-agnostic and rare-indication approvals across regulators, A standard for tumour-agnostic approvals: minimum histologies and hierarchical modelling, Larotrectinib.
- TermGene fusion
Shares A standard for tumour-agnostic approvals: minimum histologies and hierarchical modelling, Driver mutation (actionable / targetable alteration), Larotrectinib, Entrectinib.
- TermBasket, umbrella, and platform trials
Shares Pancreatic Cancer Action Network (PanCAN), Adopt tumour-agnostic cancer drug labels across regions by reliance, not re-review, Off-label, A standard for tumour-agnostic approvals: minimum histologies and hierarchical modelling.
- TargetRET
Shares Adopt tumour-agnostic cancer drug labels across regions by reliance, not re-review, Reciprocal recognition of tumour-agnostic and rare-indication approvals across regulators, A standard for tumour-agnostic approvals: minimum histologies and hierarchical modelling, Selpercatinib.
- TargetBRAF
Shares Adopt tumour-agnostic cancer drug labels across regions by reliance, not re-review, Reciprocal recognition of tumour-agnostic and rare-indication approvals across regulators, BRAF V600E mutation, A standard for tumour-agnostic approvals: minimum histologies and hierarchical modelling.
- TermMicrosatellite instability (MSI-H) / mismatch repair deficiency (dMMR)
Shares WRN inhibitors: a second synthetic-lethal win for mismatch-repair cancers, A standard for tumour-agnostic approvals: minimum histologies and hierarchical modelling, Le 2015: PD-1 blockade works in tumours with mismatch-repair deficiency, whatever the organ, Le 2017: mismatch-repair deficiency predicts response to PD-1 blockade across twelve tumour types, leading to the first tissue-agnostic drug approval.
- PersonDung T. Le
Shares Le 2015: PD-1 blockade works in tumours with mismatch-repair deficiency, whatever the organ, Le 2017: mismatch-repair deficiency predicts response to PD-1 blockade across twelve tumour types, leading to the first tissue-agnostic drug approval, Pembrolizumab, Colorectal cancer.
- PersonLuis A. Diaz Jr.
Shares Le 2015: PD-1 blockade works in tumours with mismatch-repair deficiency, whatever the organ, Le 2017: mismatch-repair deficiency predicts response to PD-1 blockade across twelve tumour types, leading to the first tissue-agnostic drug approval, Pembrolizumab, Colorectal cancer.