{"entity":{"id":"paper-halo-301-pegvorhyaluronidase-jco-2020","kind":"paper","name":"Randomized Phase III Trial of Pegvorhyaluronidase Alfa With Nab-Paclitaxel Plus Gemcitabine for Patients With Hyaluronan-High Metastatic Pancreatic Adenocarcinoma","aka":[],"tldr":"The 2020 trial of an enzyme meant to dissolve the dense matrix around pancreatic tumours so chemotherapy could reach them: more tumours shrank, but patients lived no longer, and the drug was abandoned.","summary":"HALO 109-301 was a phase 3, randomised, double-blind, placebo-controlled trial in untreated, metastatic, hyaluronan-high pancreatic ductal adenocarcinoma. Patients were randomised 2:1 to pegvorhyaluronidase alfa (PEGPH20, 3.0 micrograms per kilogram twice weekly in cycle 1 then weekly) plus nab-paclitaxel and gemcitabine, or placebo plus the same chemotherapy; 494 were randomised and 492 analysed (327 versus 165). With 330 deaths, median overall survival was 11.2 versus 11.5 months (hazard ratio 1.00, 95 percent confidence interval 0.80 to 1.27, P = 0.97); median progression-free survival 7.1 versus 7.1 months; objective response 47 versus 36 percent. Grade 3 or higher fatigue (16.0 versus 9.6 percent), muscle spasms (6.5 versus 0.6) and hyponatraemia (8.0 versus 3.8) were commoner with PEGPH20. The authors concluded the results do not support further development.","asOf":"2026-09-24","links":[{"label":"J Clin Oncol 2020","url":"https://doi.org/10.1200/JCO.20.00590"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/32706635/"},{"label":"ClinicalTrials.gov NCT02715804","url":"https://clinicaltrials.gov/study/NCT02715804"},{"label":"Trial design rationale (Future Oncol 2018)","url":"https://doi.org/10.2217/fon-2017-0338"}],"tags":["pancreatic-evidence"],"related":["paper-ozdemir-caf-depletion-accelerates-pancreatic-cancer-cancer-cell-2014","paper-mpact-nab-paclitaxel-gemcitabine-nejm-2013"],"cancers":["pancreatic","metastatic-pdac"],"sections":[],"technologies":[],"targets":[],"drugs":["gemcitabine-nab-paclitaxel"],"companies":[],"institutions":[],"pathways":[],"terms":["desmoplasia","desmoplastic-stroma-rich"],"trials":[],"people":["eric-van-cutsem"],"bottlenecks":["b-negative-results","b-tme-immunosuppression"],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2020,"doi":"10.1200/JCO.20.00590","pmid":"32706635","authors":"Van Cutsem E, Tempero MA, Sigal D, et al.","paperType":"rct","findings":["492 patients analysed, hyaluronan-high, 2:1 randomisation, double-blind.","Median overall survival 11.2 versus 11.5 months (hazard ratio 1.00); progression-free survival 7.1 versus 7.1 months.","Objective response 47 versus 36 percent.","More grade 3 or higher fatigue, muscle spasms and hyponatraemia with PEGPH20."],"whatItMeans":"The definitive negative result for first-generation stromal targeting: a biomarker-selected population, a drug that did what it was designed to do to the matrix, and no survival benefit; the stroma ideas on this page start from here.","caveats":["Hyaluronan-high selection by a companion assay; the result does not exclude other stromal targets.","Response rate rose without survival, a pattern seen again with other pancreatic agents."],"changedPractice":true,"participants":494},"route":"/key-papers/paper-halo-301-pegvorhyaluronidase-jco-2020/","neighbours":{"paper":[{"id":"paper-ozdemir-caf-depletion-accelerates-pancreatic-cancer-cancer-cell-2014","kind":"paper","name":"Depletion of carcinoma-associated fibroblasts and fibrosis induces immunosuppression and accelerates pancreas cancer with reduced survival","route":"/key-papers/paper-ozdemir-caf-depletion-accelerates-pancreatic-cancer-cancer-cell-2014/"},{"id":"paper-mpact-nab-paclitaxel-gemcitabine-nejm-2013","kind":"paper","name":"MPACT (Von Hoff 2013): nab-paclitaxel plus gemcitabine for metastatic pancreatic cancer","route":"/key-papers/paper-mpact-nab-paclitaxel-gemcitabine-nejm-2013/"},{"id":"paper-van-cutsem-j-clin-oncol","kind":"paper","name":"Randomized Phase III Trial of Pegvorhyaluronidase Alfa With Nab-Paclitaxel Plus Gemcitabine for Patients With Hyaluronan-High Metastatic Pancreatic Adenocarcinoma","route":"/key-papers/paper-van-cutsem-j-clin-oncol/"}],"cancer":[{"id":"metastatic-pdac","kind":"cancer","name":"Metastatic pancreatic ductal adenocarcinoma","route":"/cancers/metastatic-pdac/"},{"id":"pancreatic","kind":"cancer","name":"Pancreatic ductal adenocarcinoma","route":"/cancers/pancreatic/"}],"drug":[{"id":"gemcitabine-nab-paclitaxel","kind":"drug","name":"Gemcitabine + nab-paclitaxel","route":"/drugs/gemcitabine-nab-paclitaxel/"}],"term":[{"id":"desmoplasia","kind":"term","name":"Desmoplasia (tumour stroma)","route":"/terms/desmoplasia/"},{"id":"desmoplastic-stroma-rich","kind":"term","name":"Stroma-rich and desmoplastic tumours in molecular data","route":"/terms/desmoplastic-stroma-rich/"}],"person":[{"id":"eric-van-cutsem","kind":"person","name":"Eric Van Cutsem","route":"/people/eric-van-cutsem/"}],"bottleneck":[{"id":"b-tme-immunosuppression","kind":"bottleneck","name":"Cold tumours and the immunosuppressive microenvironment","route":"/bottlenecks/b-tme-immunosuppression/"},{"id":"b-negative-results","kind":"bottleneck","name":"Failures are hidden","route":"/bottlenecks/b-negative-results/"}],"journal":[{"id":"jco","kind":"journal","name":"Journal of Clinical Oncology","route":"/journals/jco/"}],"roadmap":[{"id":"pancreatic-roadmap","kind":"roadmap","name":"Pancreatic cancer roadmap: from Whipple's operation to gemcitabine, FOLFIRINOX, adjuvant chemotherapy, PARP inhibition, KRAS inhibition, vaccines and the surveillance question","route":"/roadmaps/pancreatic-roadmap/"}],"idea":[{"id":"idea-pdac-stromal-reprogramming-not-depletion","kind":"idea","name":"Reprogramme the stroma rather than remove it: second-generation stromal trials with a stromal biomarker and a survival endpoint","route":"/ideas/idea-pdac-stromal-reprogramming-not-depletion/"}]}}