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Phase 2 Study Assessing Tolerability, Efficacy, and Biomarkers for Durvalumab ± Tremelimumab and Gemcitabine/Cisplatin in Chemo-Naïve Advanced BTC

Web Exclusives — May 30, 2020

Immunotherapies have shown early promising efficacy in some patients with biliary tract cancer (BTC). The authors assessed durvalumab (D) (anti–PD-L1) ± tremelimumab (T) (anti–CTLA-4), and gemcitabine/cisplatin (GemCis) as first-line treatment in Korean patients with BTC. The research team also performed an extensive biomarker analysis.1

Patients were first enrolled in the biomarker cohort to receive 1 cycle of gemcitabine 1000 mg/m2 + cisplatin 25 mg/m2 on days 1 and 8, followed by GemCis + D 1120 mg and tremelimumab 75 mg, every 3 weeks until disease progression. Subsequent patients were allocated to GemCis + D (3-combo cohort) or GemCis + D+T (4-combo cohort) until disease progression. In all cohorts, tumor biopsies were obtained pretreatment, after 1 cycle, and at disease progression. Blood samples for circulating tumor DNA were obtained at every cycle. Tumor mutational burden was assessed on pretreatment tumor samples, and PD-L1 expression was assessed on pre- and post-treatment tumor biopsy samples. A total of 121 patients were enrolled. Median follow-up durations were 28.5 months, 11.3 months, and 11.9 months in the biomarker cohort, 3-combo cohort, and 4-combo cohort arms, respectively.

Objective response rate and median overall survival were improved in cohorts 3 and 4 compared with the biomarker cohort. The most common adverse events (any grade) were nausea (59.5%), neutropenia (54.5%), and pruritus (54.5%). Candidate biomarkers were identified that may be indicative of response to these therapies. The most common grade 3/4 events were neutropenia (50.4%), anemia (35.5%), and thrombocytopenia (16.5%). The addition of immunotherapy to chemotherapy was tolerable and showed very promising efficacy. The combination of D + Gem/Cis is being investigated in the global phase 3 TOPAZ-1 trial (NCT03875235). number NCT03046862.


  1. Oh D-Y, et al. ASCO 2020. Abstract 4520.

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