Final analysis of a multicenter, open-label, phase 2 study evaluating the efficacy and safety of tislelizumab (TIS) in combination with fruquintinib (F) in patients (pts) with selected solid tumors.
Year: 2025
Type: conference-abstract
Abstract: 2604 Background: Immunotherapy in combination with antiangiogenic agents has shown promising antitumor activity compared with either agent alone. We report efficacy and safety data from the final analysis of the phase 2 BGB-A317-Fruquintinib-201 trial evaluating the programmed cell death-1 antibody TIS combined with the selective vascular endothelial growth factor receptor (VEGFR)-1, -2, and -3 inhibitor F in pts with advanced solid tumors. Methods: This was an open-label, multicenter, two-part study with a safety run-in followed by dose-expansion. Eligible pts were adults with advanced or metastatic unresectable gastric cancer (GC), microsatellite stable colorectal cancer (MSS CRC), or locally advanced surgery-/radiotherapy-ineligible and programmed death ligand-1–positive (PD-L1+; defined as PD-L1 ≥1%) stage IIIB/IV non-small cell lung cancer (NSCLC). F 5 mg daily (3 weeks on, 1 week off) plus TIS (300 mg IV Q4W) was administered as second-line therapy for pts with GC, third-line therapy for pts with MSS CRC, and first-line therapy for pts with PD-L1+ NSCLC. The primary outcome measure was overall response rate (ORR) per RECIST v1.1. Secondary endpoints included other efficacy measures and safety. Results: The median study follow-up was 11.6 months (mo; range, 0.4-32.8). A total of 84 pts were enrolled (GC, n=31; MSS CRC, n=31; PD-L1+ NSCLC, n=22). One study treatment component-related death was reported in the GC cohort and 1 in the PD-L1+ NSCLC cohort. The recommended phase 2 dose was established at F 5 mg daily (3 weeks on, 1 week off) in combination with TIS with no observed dose-limiting toxicities. Efficacy and safety are reported in the Table. Any-grade treatment-emergent adverse events (TEAEs) occurred in 83 (98.8%) pts; proteinuria (32.1%), hypoalbuminemia (27.4%), and hypothyroidism (25.0%) were most common. 9/32 (10.7%) pts had grade ≥3 immune-mediated AEs. Conclusions: Despite the limited sample size, TIS+F demonstrated moderate antitumor activity in pts with advanced solid tumors, with manageable safety observed in pts with GC and MSS CRC. Further investigation of TIS+F is warranted in the GC and MSS CRC settings. Clinical trial information: NCT04716634 . GC (N=31) MSS CRC (N=31) PD-L1+ NSCLC (N=22) ORR, n (%) 4 (12.9) 3 (9.7) 9 (40.1) Disease control rate, n (%) 23 (74.2) 23 (74.2) 15 (68.2) Clinical benefit rate, n (%) 10 (32.3) 12 (38.7) 13 (59.1) Median progression-free survival, mo (95% CI) 4.6 (3.4, 7.4) 4.6 (3.6, 7.2) 15.6 (1.8, NE) Median overall survival, mo (95% CI) 10.5 (5.2, 14.6) 10.0 (4.7, 15.2) NR (6.0, NE) Median duration of response, mo (95% CI) NR (5.6, NE) 11.9 (3.7, NE) NR (7.7, NE) Grade ≥3 TRAE, n (%) 10 (32.3) 12 (38.7) 14 (63.6) Serious TRAE, n (%) 3 (9.7) 3 (9.7) 9 (40.9) TEAE leading to discontinuation of any study treatment, n (%) 5 (16.1) 3 (9.7) 7 (31.8) CI, confidence interval; NE, not evaluable; NR, not reached.
Source: Journal of Clinical Oncology
Authors: Keun-Wook Lee, Yanqiao Zhang, Hongqiang Guo, Zhiyong He, Jianhua Shi, Zinan Bao, Ramil Abdrashitov, Zhang Zhang, Feng Bi
Institutions: Seoul National University, Seoul National University Bundang Hospital, Harbin Medical University, Third Affiliated Hospital of Harbin Medical University, Henan Cancer Hospital, Fujian Provincial Cancer Hospital, Sichuan University, West China Medical Center of Sichuan University, West China Hospital of Sichuan University
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W4410805526