A phase II study of re-introduction of gemcitabine plus cisplatin in combination with durvalumab after durvalumab maintenance therapy in patients with unresectable or recurrent biliary tract cancer (PRIDE study).

TPS609 Background: Biliary tract cancer (BTC) is an aggressive malignancy with limited treatment options and poor prognosis. The phase III TOPAZ-1 trial established gemcitabine plus cisplatin (GC) with durvalumab (GCD), followed by durvalumab maintenance, as a global first-line therapy. Nevertheless, most patients ultimately experience disease progression during maintenance therapy, and no universally accepted second-line regimen exists. In TOPAZ-1, GC was limited to eight cycles before durvalumab maintenance, so progression during this GC-free interval does not necessarily indicate GC failure but may reflect preserved platinum sensitivity. Retrospective studies have indicated that re-introduction of platinum-based chemotherapy may benefit platinum-sensitive disease in BTC. Therefore, reintroduction of GC therapy in this context is expected to improve prognosis. However, prospective evidence in this post-GCD setting is lacking. We therefore conducted a phase II trial to evaluate the efficacy and safety of GC re-introduction with durvalumab in patients with unresectable or recurrent BTC after progression during the GC-free interval of durvalumab maintenance. Methods: This is a prospective, multicenter, single-arm phase II study (PRIDE). Eligible patients must have histologically or cytologically confirmed adenocarcinoma of the intrahepatic or extrahepatic bile duct, gallbladder, or ampulla of Vater; unresectable or recurrent disease; ECOG performance status 0–1; and were refractory to durvalumab maintenance therapy after receiving ≥8 doses of cisplatin in first-line GCD. Patients will receive 3-week cycles of gemcitabine (1000 mg/m²) and cisplatin (25 mg/m²) on days 1 and 8, in combination with durvalumab (1500 mg) administered on day 1. Treatment will continue until disease progression, unacceptable toxicity, or patient withdrawal, with dose modifications permitted per protocol. The primary endpoint is the 6-month survival rate. Secondary endpoints include overall survival, progression-free survival, objective response rate, disease control rate, duration of response, and safety. Survival distributions will be estimated using the Kaplan–Meier method, and the 6-month survival rate with its 95% confidence interval will be calculated using Greenwood’s formula. The planned sample size is 29 patients, based on an expected 6-month survival rate of 60% in a platinum-sensitive population, with the anticipated benefit considered at least comparable to the historical 50.6% observed with second-line FOLFOX. Patient enrollment will be conducted over 18 months, with a minimum follow-up of 6 months after the last patient is enrolled. The study period is scheduled from May 2025 to April 2028. Clinical trial information: jRCTs031250085 .