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.

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.