A Study to Evaluate the Efficacy and Safety of Standard-of-Care Chemotherapy and Bevacizumab With or Without INCA33890 in the First-Line Treatment of Metastatic Microsatellite Stable Colorectal Cancer

Primary Outcome Measures

1. Progression-Free Survival (PFS)
   Defined as the time from the date of randomization to the date of the first documented progression as determined by the investigator per Response Evaluation Criteria in Solid Tumours (RECIST) v1.1 or death due to any cause.

Secondary Outcome Measures

1. Overall Survival (OS)
   Defined as the time from the date of randomization to the date of death due to any cause.
2. Objective response
   Defined as complete response (CR) or partial response (PR) as determined by the investigator per RECIST v1.1.
3. Duration of Response (DOR)
   Defined as the time from the earliest date of documented response until the earliest date of disease progression as determined by the investigator per RECIST v1.1 or death due to any cause, whichever occurs first.
4. Treatment Emergent Adverse Events (TEAEs)
   Adverse events reported for the first time or worsening of a pre-existing event after first dose of study treatment, up to 90 days after the last dose INCA33890/placebo (or 30 days after the last dose of any FOLFOX component or bevacizumab if later) or the start of new anticancer therapy, whichever comes first.
5. TEAEs leading to dose interruptions, dose reductions or discontinuation of study treatmen
   TEAEs leading to dose interruption or study drug discontinuation.
6. Change from baseline in EQ-5D-5L score at protocol-defined visits
   The EQ-5D-5L is a validated, self-reported instrument for assessing HRQoL across 5 dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension has 5 response levels of severity, ranging from no problems to extreme problems. The questionnaire also includes a visual analog scale for self-rated overall health on a scale from 0 (worst imaginable health) to 100 (best imaginable health).
7. Change from baseline in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ)-Core 30 (C30) at protocol-defined visits
   The EORTC QLQ-C30 is a validated, self-administered questionnaire developed to assess the quality of life in cancer patients. It consists of 30 questions divided into several subscales, including 5 functional scales (physical, role, cognitive, emotional, and social), 3 symptom scales (fatigue, nausea and vomiting, and pain), a global health status/QoL scale, and a number of single-item measures that assess additional symptoms such as dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties.
8. Change from baseline in Functional Assessment of Cancer Therapy Colorectal Symptom Index (FCSI)-9 score at protocol-defined visits
   The FCSI-9 is a 9-item questionnaire derived from the FACT-C questionnaire to be a briefer, more targeted symptom-specific measure for patients with CRC. The FCSI-9 assesses common symptoms of CRC, including energy, pain, weight loss, nausea, diarrhea, swelling or cramps in the stomach area, appetite, ability to enjoy life, and overall quality of life. The questionnaire is scored to produce a single total score, with a higher score indicating less symptoms.