636P Combination therapy of envafolimab, suvemcitug, and FOLFIRI in patients with metastatic microsatellite stable (MSS) or mismatch-repair proficient (pMMR) colorectal cancer: Results from a phase II clinical trial

Envafolimab is a humanized single-domain anti- PD-L1 antibody which is administered subcutaneously (SC). Suvemcitug is a humanized monoclonal antibody against vascular endothelial growth factor (VEGF). This study aims to assess the efficacy and safety of the combination of envafolimab and suvemcitug with chemotherapy as second-line or later therapy in patients (pts) with advanced or recurrent MSS/ pMMR mCRC. This was an open-label, multi-cohort, multicenter, phase II trial conducted in China. Eligible pts had received at least one prior line of treatment for MSS/pMMR mCRC and were treated with envafolimab plus suvemcitug and FOLFIRI (Irinotecan, Leucovorin, and 5-Fluorouracil). The primary endpoint was objective response rate (ORR). Secondary endpoints included duration of overall response (DoR), disease control rate (DCR), and progression-free survival (PFS) and safety. As of March 31,2023, 20 pts with MSS/pMMR mCRC were enrolled. 25.0% pts (5/20) received two prior therapies and 50.0% pts (10/20) were prior treated with antiangiogenic agents. The confirmed ORR was 25.0% (95% CI 8.7%-49.1%). DCR was 90.0% (95% CI 68.3%-98.8%). With a median follow-up time of 8.0 months (IQR 6.9-9.8), the median PFS was 5.6 months (95% CI 4.01-7.59) and DoR was 4.1 months (95% CI 3.02-NE). The most common grade ≥ 3 TRAEs were neutrophil count decreased (60.0%) and leucopenia (25.0%). No death was reported. Both envafolimab and suvemcitug showed similar pharmacokinetic profile to monotherapy. Biomarker analysis suggested APC wild type or TP53 mutation were associated with poor efficacy, while KRAS, PI3KCA, BRAC2, SMAD4 and AR mutations, which reported with poor response to immunotherapies, had no effect on the response. To the best of our knowledge, this is the first study demonstrated promising antitumor activity and a manageable safety profile of immunotherapy plus anti-angiogenic agent and chemotherapy in pts with MSS/ pMMR mCRC who had failed at least one line of therapy. The results support further evaluation of the therapy in a larger population.