A phase 1b/2 trial of gemcitabine, cisplatin, nab-paclitaxel, and tislelizumab (GENTIS) in patients with advanced biliary tract cancer
Presenter: Hong Jae Chon, MD Session: Phase I Clinical Trials in Progress Time: 4/20/2026 9:00:00 AM → 4/20/2026 12:00:00 PM
Authors
Hong Jae Chon 1 , Ilhwan Kim 2 , Jin Won Kim 3 , Minsu Kang 3 , Myung-Ah Lee 4 , Hye Jin Choi 5 , Choong-kun Lee 6 , Woo Kyun Bae 7 , Jung Yong Hong 8 , Seonjeong Woo 9 , Ho Yeong Lim 1 , Beodeul Kang 1 , Jung Sun Kim 1 , Chan Kim 1 1 Division of Medical Oncology, Department of Internal Medicine, CHA Bundang Medical Center, CHA University School of Medicine, Seongnam, Korea, Republic of, 2 Division of Oncology, Department of Internal Medicine, Haeundae Paik Hospital, Inje University College of Medicine, Busan, Korea, Republic of, 3 Department of Internal Medicine, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Korea, Republic of, 4 Division of Medical Oncology, Department of Internal Medicine, Seoul St. Mary’s Hospital, College of Medicine, Cancer Research Institute, The Catholic University of Korea, Seoul, Korea, Republic of, 5 Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea, Republic of, 6 Division of Medical Oncology, Yonsei Cancer Center, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea, Republic of, 7 Department of Hemato-Oncology, Chonnam National University Medical School, Gwangju, Korea, Republic of, 8 Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea, Republic of, 9 Department of Life Science, CHA University, Seongnam, Korea, Republic of
Abstract
Background: Immunotherapy with gemcitabine and cisplatin (Gem/Cis) has become the standard first-line treatment for advanced biliary tract cancer (BTC), but survival gains remain modest. Although nab-paclitaxel (nab-P) in combination with Gem/Cis showed promising efficacy in a phase II trial, it failed to demonstrate survival benefit in a subsequent phase III trial due to the toxicity associated with the high-dose regimen. Based on these findings, we designed the GENTIS trial to evaluate Gem/Cis in combination with tislelizumab (anti-PD-1) and optimized dose nab-P, aiming to enhance efficacy while maintaining tolerability in treatment-naïve patients with advanced BTC. Here, we present the phase 1b safety results of the GENTIS trial. Material and Methods: Patients with locally advanced or metastatic BTC were dosed in the GENTIS (NCT06893380). The phase 1b part followed a 3 + 3 dose-escalation design. All patients received tislelizumab 200 mg on day 1, gemcitabine 1000 mg/m², cisplatin 25 mg/m², and nab-P at 50-100 mg/m² on days 1 and 8 of a 21-day cycle. Planned dose levels of nab-P were Level −1 (50 mg/m²), Level 0 (75 mg/m²; starting dose), and Level +1 (100 mg/m²). Dose escalation proceeded from Level 0 to Level +1 if no dose-limiting toxicities (DLTs) were observed among the initial 3 patients at Level 0. DLTs were evaluated during the first cycle of study treatment. Results: Six patients were enrolled in phase 1b part: intrahepatic (50.0%), extrahepatic (16.7%), and gallbladder cancer (33.3%); most had metastatic disease (83.3%). All received at least one dose of the combination of Gem/Cis, nab-P, and tislelizumab: 3 at Level 0 (75 mg/m²) and 3 at Level +1 (100 mg/m²) of nab-P. Through the data cutoff of November 6, 2025, patients received 3-9 cycles, with all patients ongoing on treatment. No DLTs were observed. Treatment-related adverse events (TRAEs) of any grade occurred in 5 patients (83.3%), and grade 3 in 3 patients (50.0%); no grade 4-5 TRAEs were observed. The most frequent TRAEs were neutropenia in 3 patients (50.0%) and anemia, increased creatinine, and urticaria in 2 patients (33.3%). Serious adverse events occurred in one patient (16.7%; biliary tract infection), which was not treatment-related and resolved. Median follow-up was 3.8 months at the time of the data cutoff; the confirmed objective response rate was 66.7% (4 partial responses), and the disease control rate was 100% (including 2 stable diseases). As no DLTs were observed and long-term tolerability was considered, the RP2D of nab-P in combination with Gem/Cis and tislelizumab was 75 mg/m². Conclusion: The combination of Gem/Cis, tislelizumab and dose-optimized nab-P showed a manageable safety profile and promising clinical outcomes in patients with advanced BTC and is now being investigated in the phase 2 expansion at the RP2D of nab-P 75 mg/m².
Disclosure
H. Chon, None.. I. Kim, None.. J. Kim, None.. M. Kang, None.. M. Lee, None.. H. Choi, None.. C. Lee, None.. W. Bae, None.. J. Hong, None.. S. Woo, None.. H. Lim, None.. B. Kang, None.. J. Kim, None.. C. Kim, None.
Cited in
Control: 9728 · Presentation Id: 12182 · Meeting 21436