A phase Ib/III randomized double-blinded placebo-controlled study of suvemcitug combined with trifluridine/tipiracil for refractory metastatic colorectal cancer.

TPS3674 Background: Colorectal cancer (CRC) is a leading cause of cancer-related death worldwide. For patients with metastatic CRC (mCRC) that has progressed on standard chemotherapies, available treatments offer limited benefit. Notably, the phase III SUNLIGHT trial demonstrated the efficacy and safety of trifluridine/tipiracil (FTD/TPI) in combination with bevacizumab in refractory mCRC. Suvemcitug is a new-generation recombinant humanized anti-VEGF rabbit monoclonal antibody. In the previous clinical trials, suvemcitug demonstrated its favorable safety profile and efficacy signals as a single agent or in combination with chemotherapy for the treatment of mCRC. This study aims to assess the efficacy and safety of the combination of suvemcitug and FTD/TPI in patients with refractory mCRC. Methods: This phase Ib/III, randomized, double-blinded, placebo-controlled, multi-cohort study (NCT07361003) consists of two parts, Part 1 (phase Ib) and Part 2 (phase III). Estimated total enrollment is approximately 464 participants: 30 for Part 1 and 434 for Part 2. Patients with mCRC are eligible for participation if they have received chemotherapy based on fluoropyrimidine, oxaliplatin and irinotecan, and have either previously received or are unsuitable for anti-VEGF therapy and anti-EGFR therapy (if RAS wild-type). Part 1: Phase Ib: Participants will be enrolled to receive suvemcitug combined with FTD/TPI. The dose of suvemcitug is 1.5 mg/kg administrated intravenously every two weeks. The primary endpoint is safety and tolerability of suvemcitug. The secondary endpoints include pharmacokinetic (PK) profile of suvemcitug; the incidence, duration, and titer of anti-drug antibodies (ADA); as well as objective response rate (ORR), duration of response (DoR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS). Part 2: Phase III: Part 2 is designed as a Phase III to further evaluate the antitumor activity of suvemcitug in combination with FTD/TPI in refractory mCRC. Eligible participants will be randomized (1:1 ratio) to receive FTD/TPI in combination with suvemcitug or matching placebo at the dose identified in Part 1. Stratification criteria include primary tumor location, prior bevacizumab exposure, and time from initial metastasis to enrollment. The primary endpoint is OS. The secondary endpoints include PFS, ORR, DoR, DCR, safety, quality of life, PK and immunogenicity (ADA incidence, titer, duration). The exploratory endpoints are correlations among PK, pharmacodynamics, safety and clinical efficacy. Study treatment will continue until progressive disease, unacceptable toxicity, withdrawal of consent, or the investigator’s decision to discontinue. Clinical trial information: NCT07361003 .