Phase 3 Randomized Double-Blind Study of INCA33890 Plus First-Line Chemotherapy and Bevacizumab in Metastatic Microsatellite Stable Colorectal Cancer

The primary objective is to evaluate the efficacy of INCA33890 plus standard-of-care therapy versus placebo plus standard-of-care therapy in first-line treatment of metastatic microsatellite stable colorectal cancer, with clinical relevance focused on determining whether addition of INCA33890 improves antitumor outcomes over standard treatment alone. Secondary objectives are to further evaluate efficacy in the overall population and to assess safety and tolerability of the INCA33890 regimen versus placebo. Additional secondary evaluation includes changes from baseline in health-related quality of life assessments.

The trial population comprised 408 participants with metastatic microsatellite stable colorectal cancer. The study included both female and male adults, all aged 18 years or older, with histologically or cytologically confirmed stage IV metastatic colorectal adenocarcinoma that was not amenable to curative resection. The population was selected from patients with radiographically measurable disease and adequate organ function, and no prior systemic treatment for unresectable or metastatic colorectal cancer. Participants who had previously received neoadjuvant and/or adjuvant therapy could be enrolled if there had been no disease recurrence within 12 months of the last systemic therapy. Additional relevant considerations included willingness to provide written informed consent and to avoid pregnancy or fathering children. The sponsor did not provide further information on general health status, lifestyle factors, or other selection details.

The study is a randomized, double-blind, Phase 3 clinical trial evaluating standard-of-care chemotherapy and bevacizumab with or without INCA33890 in the first-line treatment of metastatic microsatellite stable colorectal cancer. Participants are assigned to receive either INCA33890 or placebo in combination with oxaliplatin, fluorouracil, calcium folinate, and bevacizumab. The overall trial duration is planned from 2026-06-01 to 2029-12-01. Study participation begins with a screening visit to confirm eligibility, including informed consent, disease confirmation, measurable disease assessment, and evaluation of organ function and other protocol-defined criteria. Eligible participants then enter the treatment period and attend follow-up visits for ongoing assessment of efficacy and safety, including progression status and treatment-emergent adverse events, until the end-of-study visit. The expected length of participant involvement is not specified in the source data. Early termination from the study may occur for disease progression, death, treatment-related toxicity requiring dose interruption or study drug discontinuation, or other protocol-defined reasons.

The investigational treatment was INCA33890, administered as an intravenous infusion at a dose of 900 mg. The trial evaluated INCA33890 in combination with standard-of-care therapy in the first-line treatment of metastatic microsatellite stable colorectal cancer. The study objective was to compare the efficacy of INCA33890 plus standard-of-care therapy versus placebo plus standard-of-care therapy.

The non-experimental treatment included a placebo formulated with the same buffer composition, 10 mM acetate, 9% (w/v) sucrose, and 0.02% (w/v) polysorbate 80, at pH 5.5, without the active pharmaceutical ingredient. Standard-of-care therapy consisted of calcium folinate as a solution for injection at 400 mg/m2, bevacizumab as an intravenous infusion at 5 mg/kg, oxaliplatin as an intravenous infusion at 85 mg/m2, and fluorouracil as a solution for infusion at 2800 mg/m2. The study was randomized and double-blind. No additional information on dosing schedule or compliance monitoring was provided.

Efficacy will be assessed by progression-free survival, defined as the time from randomization to the first documented disease progression determined by Blinded Independent Central Review per RECIST v1.1 or death due to any cause. Secondary efficacy assessments will include overall survival, objective response defined as complete response or partial response by Blinded Independent Central Review per RECIST v1.1, and duration of response defined as the time from the earliest documented response to the earliest disease progression per RECIST v1.1 or death due to any cause, whichever occurs first.