# KEYNOTE-966

Source: https://onco.cc/trials/keynote-966/  
OnCo record `keynote-966` (Trial). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

A second immunotherapy trial confirmed the modest survival benefit of adding PD-1 blockade to chemotherapy in bile duct cancer.

## Summary

KEYNOTE-966, trial NCT04003636 sponsored by Merck and reported in 2023, was the second immunotherapy trial to confirm a modest survival benefit from adding PD-1 blockade to chemotherapy in first-line advanced biliary tract cancer. It randomised 1,069 patients to pembrolizumab or placebo with gemcitabine and cisplatin, with gemcitabine continued beyond eight cycles in both arms, met its primary overall survival endpoint and led to approval in October 2023. OnCo links it to biliary tract and gallbladder cancer, pembrolizumab, gemcitabine plus cisplatin and the pairing of chemotherapy with PD-1 or PD-L1 blockade, and it replicates TOPAZ-1. Whether the modest median gain justifies routine use for every patient, given the cost, is the open question.

## Fields

- Kind: Trial
- Status: positive
- Last checked: 2026-09-07
- Registry id: NCT04003636
- Phase: 3
- Setting: First-line advanced biliary tract cancer: gemcitabine-cisplatin + pembrolizumab vs + placebo
- Sponsor: Merck
- Enrolled: 1069
- Result: OS 12.7 vs 10.9 months, HR 0.83.
- Outcomes: Overall survival: Pembrolizumab + GemCis 12.7 months vs Placebo + GemCis 10.9 months, HR 0.83
- Replication: Replicates TOPAZ-1.

## Notes

- In the UK, NICE could not appraise pembrolizumab with gemcitabine and cisplatin for biliary tract cancer because no evidence submission was made (TA966, terminated), so the routinely funded NHS immunotherapy partner is durvalumab (TA944).
- Gallbladder cancer: eligibility was intrahepatic or extrahepatic cholangiocarcinoma or gallbladder cancer and randomisation was stratified by site of origin (gallbladder, intrahepatic or extrahepatic), geographic region and disease stage; the proportion with gallbladder cancer and the gallbladder hazard ratio are in the Lancet paper's tables rather than its abstract and are not quoted here. UK sites: Aberdeen, Belfast, Coventry, London (Royal Free, Royal Marsden, Hammersmith), Manchester and Sutton (registry). NICE terminated its appraisal of pembrolizumab with gemcitabine and cisplatin for biliary tract cancer (TA966, April 2024) because no evidence submission was made, so durvalumab (TA944) is the NHS chemo-immunotherapy option.

## Sources

- ClinicalTrials.gov NCT04003636: https://clinicaltrials.gov/study/NCT04003636
- NICE TA966: pembrolizumab with gemcitabine and cisplatin for untreated advanced biliary tract cancer (terminated appraisal): https://www.nice.org.uk/guidance/terminated/ta966
- NICE TA966: pembrolizumab with gemcitabine and cisplatin for biliary tract cancer (terminated appraisal, 2024): https://www.nice.org.uk/guidance/terminated/ta966

## Connected records

- cancers: [Biliary tract cancer (cholangiocarcinoma)](https://onco.cc/cancers/cholangiocarcinoma/), [Extrahepatic cholangiocarcinoma (perihilar and distal)](https://onco.cc/cancers/extrahepatic-cholangiocarcinoma/), [Gallbladder adenocarcinoma](https://onco.cc/cancers/gallbladder-adenocarcinoma/), [Gallbladder cancer](https://onco.cc/cancers/gallbladder/), [Intrahepatic cholangiocarcinoma](https://onco.cc/cancers/intrahepatic-cholangiocarcinoma/)
- technologies: [Immune checkpoint inhibitors](https://onco.cc/technologies/checkpoint-inhibitor/)
- drugs: [Gemcitabine + cisplatin](https://onco.cc/drugs/gemcitabine-cisplatin/), [Pembrolizumab](https://onco.cc/drugs/pembrolizumab/)
- companies: [Merck & Co. (MSD)](https://onco.cc/companies/merck/)
- key papers: [KEYNOTE-966: pembrolizumab plus gemcitabine and cisplatin for advanced biliary tract cancer](https://onco.cc/key-papers/paper-keynote-966-lancet-2023/)
- pairings: [Gemcitabine-cisplatin + PD-(L)1 blockade in biliary cancer](https://onco.cc/pairings/gemcis-plus-io-btc/)
- terms: [A clinical trial or standard treatment for gallbladder cancer](https://onco.cc/terms/trial-or-standard-treatment-biliary/), [Gallbladder cancer in biliary tract cancer trials (eligibility and subgroups)](https://onco.cc/terms/gallbladder-cancer-in-biliary-trials/)
- roadmaps: [Gallbladder cancer roadmap: from a chance finding at gallstone surgery to a disease with its own trials](https://onco.cc/roadmaps/gallbladder-cancer-roadmap/)
- ideas: [Report gallbladder cancer as its own population in every biliary trial](https://onco.cc/ideas/idea-gbc-report-gallbladder-separately-in-biliary-trials/)

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