{"entity":{"id":"keynote-158","kind":"trial","name":"KEYNOTE-158","aka":[],"tldr":"The basket trial that showed pembrolizumab alone rarely works in bile duct and gallbladder cancer: only 6 of 104 patients responded, though those who did stayed in response for years. It is also the trial behind the tumour-agnostic approvals of pembrolizumab for mismatch-repair-deficient and high mutation-burden cancers, which do apply to gallbladder cancer.","summary":"KEYNOTE-158 (NCT02628067) is Merck's multi-cohort phase 2 of pembrolizumab 200 mg every three weeks in advanced solid tumours. Its biliary adenocarcinoma cohort enrolled 104 patients with incurable gallbladder or bile duct cancer (ampulla of Vater excluded) that had progressed after standard treatment, regardless of PD-L1 status. Objective response by independent central review was 5.8 percent (6 of 104; 95 percent confidence interval 2.1 to 12.1), median duration of response was not reached (range 6.2 to more than 26.6 months), and median overall and progression-free survival were 7.4 and 2.0 months; response was 6.6 percent in PD-L1 expressers and 2.9 percent in non-expressers. Grade 3 to 5 treatment-related adverse events occurred in 13.5 percent with one grade 5 renal failure. The companion KEYNOTE-028 cohort (24 PD-L1-positive patients) responded in 13 percent. The same trial's mismatch-repair-deficient and tumour mutational burden cohorts underpinned the tumour-agnostic FDA approvals of pembrolizumab (2017 and 2020), which are the route to single-agent immunotherapy for the small minority of gallbladder cancers with those features; for the rest, checkpoint blockade works only in combination with gemcitabine and cisplatin (TOPAZ-1, KEYNOTE-966).","status":"active","asOf":"2026-09-24","links":[{"label":"ClinicalTrials.gov NCT02628067","url":"https://clinicaltrials.gov/study/NCT02628067"},{"label":"Piha-Paul et al., Int J Cancer 2020: pembrolizumab for advanced biliary cancer, KEYNOTE-158 and KEYNOTE-028","url":"https://doi.org/10.1002/ijc.33013"}],"tags":[],"related":[],"cancers":["gallbladder","cholangiocarcinoma","biliary-tract-cancer"],"sections":[],"technologies":["checkpoint-inhibitor"],"targets":["pd1"],"drugs":["pembrolizumab"],"companies":["merck"],"institutions":[],"pathways":[],"terms":["tumour-agnostic","basket-umbrella-platform","msi","tmb"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-keynote-158-j-clin-oncol-2019","paper-keynote-158-ann-oncol-2022-update"],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT02628067","phase":"2","setting":"Advanced solid tumours in histology-defined and biomarker-defined cohorts, including previously treated advanced biliary adenocarcinoma of the gallbladder or biliary tree (n=104; ampullary excluded): pembrolizumab 200 mg every 3 weeks, single arm","sponsor":"Merck Sharp & Dohme","result":"Biliary cohort ORR 5.8% (6/104); median OS 7.4 months; median PFS 2.0 months; median duration of response not reached.","yearReported":2020,"enrolled":1609,"enrolledBasis":"registry","outcomes":[{"endpoint":"Objective response rate, biliary adenocarcinoma cohort (independent central review)","primary":true,"unit":"%","arms":[{"name":"Pembrolizumab","n":104,"value":5.8,"note":"95% CI 2.1 to 12.1"}],"source":"https://doi.org/10.1002/ijc.33013"},{"endpoint":"Overall survival, biliary cohort","unit":"months","arms":[{"name":"Pembrolizumab","n":104,"value":7.4}],"source":"https://doi.org/10.1002/ijc.33013"},{"endpoint":"Progression-free survival, biliary cohort","unit":"months","arms":[{"name":"Pembrolizumab","n":104,"value":2}],"source":"https://doi.org/10.1002/ijc.33013"}]},"route":"/trials/keynote-158/","neighbours":{"cancer":[{"id":"biliary-tract-cancer","kind":"cancer","name":"Biliary tract cancer (all types)","route":"/cancers/biliary-tract-cancer/"},{"id":"cholangiocarcinoma","kind":"cancer","name":"Biliary tract cancer (cholangiocarcinoma)","route":"/cancers/cholangiocarcinoma/"},{"id":"gallbladder","kind":"cancer","name":"Gallbladder cancer","route":"/cancers/gallbladder/"}],"technology":[{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}],"target":[{"id":"pd1","kind":"target","name":"PD-1","route":"/targets/pd1/"}],"drug":[{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"}],"company":[{"id":"merck","kind":"company","name":"Merck & Co. (MSD)","route":"/companies/merck/"}],"term":[{"id":"basket-umbrella-platform","kind":"term","name":"Basket, umbrella, and platform trials","route":"/terms/basket-umbrella-platform/"},{"id":"gallbladder-cancer-in-biliary-trials","kind":"term","name":"Gallbladder cancer in biliary tract cancer trials (eligibility and subgroups)","route":"/terms/gallbladder-cancer-in-biliary-trials/"},{"id":"msi","kind":"term","name":"Microsatellite instability (MSI-H) / mismatch repair deficiency (dMMR)","route":"/terms/msi/"},{"id":"tmb","kind":"term","name":"Tumour mutational burden (TMB)","route":"/terms/tmb/"},{"id":"tumour-agnostic","kind":"term","name":"Tumour-agnostic (tissue-agnostic) approval","route":"/terms/tumour-agnostic/"}],"paper":[{"id":"paper-keynote-158-j-clin-oncol-2019","kind":"paper","name":"Efficacy and Safety of Pembrolizumab in Previously Treated Advanced Cervical Cancer: Results From the Phase II KEYNOTE-158 Study","route":"/key-papers/paper-keynote-158-j-clin-oncol-2019/"},{"id":"paper-keynote-158-ann-oncol-2022-update","kind":"paper","name":"Pembrolizumab in microsatellite instability high or mismatch repair deficient cancers: updated analysis from the phase II KEYNOTE-158 study","route":"/key-papers/paper-keynote-158-ann-oncol-2022-update/"}]}}