Abstract 394TiP
Background
Biliary tract cancer (BTC) is a heterogeneous group of malignancies and typically diagnosed at advanced stages for which curative surgery is not feasible and prognosis is poor. Gemcitabine plus cisplatin (gem/cis) is first-line standard of care for advanced BTC (aBTC) for over a decade. Adding durvalumab to gem/cis significantly improved OS compared with gem/cis alone without increase the rate of TRAEs and discontinuation rate due to adverse events (TOPAZ-1 study). In China, gemcitabine-based chemotherapy other than gem/cis are also commonly used in clinical practice. While the effect of durvalumab in combination with other gemcitabine-based chemotherapy regimens and patients with ECOG PS 2 for aBTC is unknown. At the same time, this study will provide an overview of genetic alterations in Chinese BTC patients and indicates the potential biomarkers that may correlate with study treatment.
Trial design
TopDouble is a multicenter, phase IIIb, single arm study evaluating the safety and efficacy of durvalumab in combination with gemcitabine-based chemotherapy for the first-line treatment for Chinese patients with aBTC. Approximately 115 patients with previous untreated, locally advanced or metastatic BTC will be enrolled. Key eligibility criteria include age ≥18 years; ECOG PS of 0 - 2; histologically confirmed BTC. All patients will be treated by durvalumab in combination with an investigator selected gemcitabine-based chemotherapy. Gemcitabine-based chemotherapy includes gemcitabine + oxaliplatin, gemcitabine + S1, gemcitabine + cisplatin (only for ECOG PS 2 pts) according to local practice. The primary endpoint is incidence of grade 3 or 4 possibly related adverse event (PRAE) within 6 months after the initiation of durvalumab plus gemcitabine-based chemotherapy. Secondary endpoints include overall survival, objective response rate. Exploratory endpoint will investigate baseline gene profile of tumour tissue, to characterize the different genetic alterations of China-specific BTC, and mechanisms of resistance to treatment and identify putative biomarkers of prognosis.
Clinical trial identification
NCT05924880.
Legal entity responsible for the study
AstraZeneca.
Funding
AstraZeneca.
Disclosure
All authors have declared no conflicts of interest.