1026MO A phase Ib/II study of SHR-1701 (a bifunctional anti-PD-L1/TGF-βRII agent) in combination with bevacizumab (BEV) in patients with advanced solid tumors

Accumulative evidence demonstrates that anti-angiogenesis plus immune checkpoint inhibitor (ICI) has a synergistic antitumor effect in various types of tumors. Thus, we assessed the safety and efficacy of SHR-1701 plus BEV in patients (pts) with advanced solid tumors. This is a multicenter, open-label, phase 1b/2 study. The primary objective of phase 1b part was to determine the recommended phase 2 dose (RP2D) in pts with advanced solid tumors. Phase 2 part enrolled: 1) pts with advanced gastric and gastroesophageal junction cancer (GC/GEJC), PD-L1 CPS ≥1, HER2 negative, who had not received prior systemic therapy (1L); 2) pts with advanced GC/GEJC who had received ≤2 prior systemic therapies; 3) pts with recurrent or metastatic non-squamous non-small cell lung cancer (nsqNSCLC) who had failed ≤2 lines of systemic treatment (including platinum-based chemotherapy and ICI), driver gene-negative. SHR-1701 and BEV were given once every 3-week cycle. Primary endpoint of phase 2 part was objective response rate (ORR). As of Mar 31, 2023, a total of 67 pts with advanced solid tumor were enrolled, including 19 systemic treatment-naïve GC/GEJC pts, 27 pre-treated GC/GEJC pts, and 10 nsqNSCLC pts. No DLT was observed in phase 1b part. The RP2D was determined to be SHR-1701 30 mg/kg plus BEV 15 mg/kg, Q3W. With a median follow-up of 8.4 mos, the ORR was 21.1%, 33.3%, and 10.0% in the three cohorts, respectively (Table). Treatment-related adverse events (TRAEs) occurred in 94.0% of pts. Grade 3 TRAEs were reported in 29.4% of pts, with the most common ones being anemia (5.8%), increased ALT (2.9%), and increased AST (2.9%). No grade 4/5 TRAEs were reported.Table: 1026MOEfficacy outcomesVariablesGC/GEJC (1L)GC/GEJC (≥2L)nsqNSCLCAll (n=19)CPS≥5 (n=15)All (n=27)CPS≥5 (n=9)All (n=10)Best overall response, n (%)CR001 (3.7)1 (11.1)0PR4 (21.1)4 (26.7)8 (29.6)6 (66.7)1 (10.0)SD7 (36.8)5 (33.3)5 (18.5)1 (11.1)5 (50.0)PD7 (36.8)5 (33.3)12 (44.4)1 (11.1)3 (30.0)NE1 (5.3)1 (6.7)1 (3.7)01 (10.0)ORR, % (95% CI)21.1 (6.1, 45.6)26.7 (7.8, 55.1)33.3 (16.5, 54.0)77.8 (40.0, 97.2)10.0 (0.3, 44.5)DCR, % (95% CI)57.9 (33.5-79.7)60.0 (32.3, 83.7)51.8 (32.0, 71.3)88.9 (51.8, 99.7)60.0 (26.2, 87.8)mPFS, months (95% CI)4.1 (1.3-NR)4.1 (1.4-NR）4.0 (1.4-NR)10.3 (1.3-NR)6.2 (1.3-9.9) Open table in a new tab SHR-1701 plus BEV showed encouraging antitumor activity with a favorable safety profile in pts with advanced GC/GEJC and nsqNSCLC.