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

Background

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.

Methods

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).

Results

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: 1026MO

Efficacy outcomes

Conclusions

SHR-1701 plus BEV showed encouraging antitumor activity with a favorable safety profile in pts with advanced GC/GEJC and nsqNSCLC.

Clinical trial identification

NCT04856774.

Editorial acknowledgement

Yanwen Wang (Jiangsu Hengrui Pharmaceuticals) provided editorial assistance in the writing of the abstract.

Legal entity responsible for the study

Jiangsu Hengrui Pharmaceuticals.

Funding

Jiangsu Hengrui Pharmaceuticals.

Disclosure

P. Liu, Z. Zhang, S. Wang: Financial Interests, Personal, Full or part-time Employment: Jiangsu Hengrui Pharmaceuticals. All other authors have declared no conflicts of interest.