# TOPAZ-1

Source: https://onco.cc/trials/topaz-1/  
OnCo record `topaz-1` (Trial). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

TOPAZ-1 was the first immunotherapy success in bile duct cancer, with a small median gain but a growing tail of long survivors.

## Summary

TOPAZ-1, trial NCT03875235 sponsored by AstraZeneca and reported in 2022, was the first immunotherapy success in bile duct cancer, adding durvalumab to gemcitabine and cisplatin in first-line advanced biliary tract cancer. It randomised 685 patients, met its primary overall survival endpoint with a small median gain but a growing tail of long survivors, confirmed at two years and in a three-year update in 2025, and led to approval in September 2022. OnCo links it to biliary tract and gallbladder cancer, durvalumab, gemcitabine plus cisplatin, the pairing of chemotherapy with PD-1 or PD-L1 blockade, Juan W. Valle and Do-Youn Oh, and KEYNOTE-966 with pembrolizumab reproduced the class effect. Which patients populate the durable tail, and whether a biomarker can find them in advance, is the open question.

## Fields

- Kind: Trial
- Status: positive
- Last checked: 2026-09-07
- Registry id: NCT03875235
- Phase: 3
- Setting: First-line advanced biliary tract cancer: gemcitabine-cisplatin + durvalumab vs + placebo
- Sponsor: AstraZeneca
- Enrolled: 685
- Result: OS HR 0.76; 2-year OS 23.6% vs 11.5%.
- Outcomes: Overall survival (updated): Durvalumab + GemCis 12.9 months vs Placebo + GemCis 11.3 months, HR 0.76; 24-month overall survival: Durvalumab + GemCis 23.6% vs Placebo + GemCis 11.5%; Overall survival (primary analysis): Durvalumab + GemCis vs Placebo + GemCis, HR 0.8; 36-month overall survival (3-year update, median follow-up 41.3 months): Durvalumab + GemCis 14.6% vs Placebo + GemCis 6.9%, HR 0.74
- Replication: KEYNOTE-966 (pembrolizumab) reproduced the class effect.

## Notes

- NICE TA944 recommends durvalumab with gemcitabine and cisplatin, within its marketing authorisation, for locally advanced, unresectable or metastatic biliary tract cancer in adults; this is the routinely funded first-line immunotherapy combination on the NHS.
- Gallbladder cancer: randomisation was stratified by primary tumour location (intrahepatic, extrahepatic, gallbladder) and the Imfinzi label gives the split as intrahepatic 56 percent, extrahepatic 18 percent and gallbladder 25 percent; the label and the 3-year update report benefit across all clinically relevant subgroups, with extended long-term survivors (alive 30 months or more) in 17.0 percent of the durvalumab arm and 8.7 percent of the placebo arm, but no gallbladder-specific hazard ratio is published in the sources checked. UK sites: Bristol, Cambridge, London (two), Manchester, Oxford, Romford and Sheffield (registry). NICE TA944 (10 January 2024) recommends durvalumab with gemcitabine and cisplatin for locally advanced, unresectable or metastatic biliary tract cancer, gallbladder cancer included.

## Sources

- ClinicalTrials.gov NCT03875235: https://clinicaltrials.gov/study/NCT03875235
- Updated OS (PubMed): https://pubmed.ncbi.nlm.nih.gov/38823398/
- 3-year update: https://www.journal-of-hepatology.eu/article/S0168-8278(25)02201-9/fulltext
- NICE TA944: durvalumab with gemcitabine and cisplatin for unresectable or advanced biliary tract cancer: https://www.nice.org.uk/guidance/ta944
- Imfinzi label (openFDA): TOPAZ-1 baseline tumour location: https://api.fda.gov/drug/label.json?search=openfda.brand_name:%22IMFINZI%22
- NICE TA944: durvalumab with gemcitabine and cisplatin for biliary tract cancer (10 January 2024): https://www.nice.org.uk/guidance/ta944
- TOPAZ-1 3-year overall survival update, J Hepatol 2025: https://doi.org/10.1016/j.jhep.2025.05.003

## 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: [Durvalumab](https://onco.cc/drugs/durvalumab/), [Gemcitabine + cisplatin](https://onco.cc/drugs/gemcitabine-cisplatin/)
- companies: [AstraZeneca](https://onco.cc/companies/astrazeneca/)
- people: [Do-Youn Oh](https://onco.cc/people/oh-do-youn/), [Juan W. Valle](https://onco.cc/people/juan-valle/)
- key papers: [Durvalumab or placebo plus gemcitabine and cisplatin in participants with advanced biliary tract cancer (TOPAZ-1): updated overall survival from a randomised phase 3 study](https://onco.cc/key-papers/paper-topaz-1-lancet-gastroenterol-hepatol-2024-update/), [Durvalumab plus chemotherapy in advanced biliary tract cancer: 3-year overall survival update from the phase III TOPAZ-1 study](https://onco.cc/key-papers/paper-topaz-1-three-year-survival-j-hepatol-2025/), [TOPAZ-1: durvalumab plus gemcitabine and cisplatin in advanced biliary tract cancer](https://onco.cc/key-papers/paper-topaz-1-nejm-evidence-2022/)
- 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: [Chemotherapy before the second operation for high-risk incidental gallbladder cancer](https://onco.cc/ideas/idea-gbc-neoadjuvant-for-high-risk-incidental-cancer/), [Report gallbladder cancer as its own population in every biliary trial](https://onco.cc/ideas/idea-gbc-report-gallbladder-separately-in-biliary-trials/)

---
JSON: https://onco.cc/api/v1/entities/topaz-1.json