Durvalumab with gemcitabine-based chemotherapy regimens in advanced biliary tract cancer: Primary results from the phase IIIb TOURMALINE study

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BACKGROUND & AIMS: TOPAZ-1 (NCT03875235) demonstrated improved overall survival (OS) with durvalumab plus gemcitabine and cisplatin vs. placebo plus gemcitabine and cisplatin, with a clinically manageable safety profile, in advanced biliary tract cancer (aBTC). The phase IIIb TOURMALINE study (NCT05771480) is evaluating the safety and efficacy of first-line durvalumab plus seven gemcitabine-based chemotherapy regimens in a close-to-real-world aBTC population, including participants with poor prognosis. METHODS: Participants received intravenous durvalumab 1,500 mg (first infusion: 60 minutes; subsequent infusions: 30 minutes) plus investigator's choice of one of seven gemcitabine-based chemotherapy regimens. The primary endpoint was the incidence of Grade 3/4 adverse events (AEs) possibly related to treatment (PRAEs) within 6 months of the first durvalumab dose. Secondary endpoints included progression-free survival (PFS), OS, objective response rate (ORR), and safety. RESULTS: As of 17 September 2025, 142 participants (median age, 68.0 years) had completed at least 6 months of follow-up and received at least one dose of study treatment; most had metastatic disease (72.5%). Participants received a median of nine cycles of durvalumab, and the median (IQR) follow-up was 11.63 (6.87-17.25) months. Overall, 50.7% (95% CI 42.19-59.19) of participants experienced Grade 3/4 PRAEs within 6 months of durvalumab initiation. No serious AEs of special interest resulted in death. Median PFS was 7.39 months (95% CI 6.74-9.07), median OS was 13.50 months (95% CI 11.24-20.53), and ORR was 33.1% (95% CI 25.44-41.48). CONCLUSIONS: Safety profiles of durvalumab plus seven gemcitabine-based chemotherapy regimens were clinically manageable and shortening the durvalumab infusion duration from 60 to 30 minutes did not increase infusion-related reactions. Efficacy data are indicative of potential clinical activity across treatment cohorts. These findings demonstrate the feasibility of combining durvalumab with alternative gemcitabine-based regimens in a broad aBTC population. IMPACT AND IMPLICATIONS: The choice of gemcitabine-based chemotherapy backbones for the treatment of advanced biliary tract cancer (aBTC) varies globally and their use in conjunction with immunotherapy has not been fully investigated. The TOURMALINE phase IIIb study demonstrated clinically manageable safety, and efficacy data showed potential clinical activity in a close-to-real-world population of participants with aBTC receiving durvalumab plus one of seven gemcitabine-based chemotherapy regimens. These findings point towards the feasibility of combining durvalumab with different gemcitabine-based chemotherapy regimens, even in participants with less favourable disease characteristics. CLINICALTRIALS: GOV: NCT05771480; https://clinicaltrials.gov/study/NCT05771480. CLINICAL TRIAL NUMBER: NCT05771480.

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