The purpose of this study is to learn more about a new medicine called PF-08634404, and how well it works in people with cancer of the colon or rectum (CRC)). The goal is to understand if the new study medicine, combined with chemotherapy that is approved for colorectal cancer, can help people whose cancer has spread or returned after treatments taken before.
To join the study, participants must meet the following conditions:
* Be 18 years or older. * Have colorectal cancer that has spread to other parts of your body. * Be in good enough health to receive study treatment. * Should not be pregnant before starting treatment.
Participants will be randomized (like flipping a coin) to one of 2 different treatment arms. The first arm (Arm A) will include the new medicine PF-08634404 in combination with chemotherapy that is approved for colorectal cancer, and the second arm (Arm B) will include an approved medicine for colorectal cancer, called Bevacizumab, in combination with chemotherapy that is approved for this type of cancer. Participants and their doctors will not know which arm they are being assigned to. Participants will receive all the study medications through intravenous (IV) infusions, which means the medicine is given directly into a vein. The treatment will be given in cycles, and participants may continue receiving it if it is helping and they are not experiencing serious side effects.
The medicine will be given at a clinical site, where trained medical staff will check participants during and after each treatment.
* The study is expected to last approximately 33 months for each participant. * Participants will have regular visits to the study site for treatment, health checks, and tests. * After stopping treatment, participants will return for a final visit about 30 to37 days later to check their health and review any side effects. * Follow-up will continue every 12 weeks by phone or in person or by reviewing health records to check on health status and any new treatments.
Histological or cytological confirmed colorectal adenocarcinoma.
Evidence of Stage IV metastatic disease.
No prior systemic therapy for metastatic disease.
Eastern Cooperative Oncology Group performance status (ECOG) 0-1
Locally confirmed BRAF V600E mutation
Locally confirmed microsatellite instability (MSI)-high or DNA mismatch repair deficiency (dMMR) colorectal cancer
Participants with known active symptomatic CNS lesions, including leptomeningeal metastasis, brainstem, meningeal, or spinal cord metastases or compression
Clinically significant risk of hemorrhage or fistula
Parallel
PF-08634404
DrugSolution for infusion
Bevacizumab
Biological/VaccineInjection for intravenous use
Chemotherapy
DrugInjection for intravenous use
Progression-free survival (PFS) per Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1) by Blinded Independent Central Review (BICR)
Progression-free survival is defined as the time from the date of randomization to the date of the first documentation of objective progressive disease (PD) assessed by BICR per RECIST 1.1, or death due to any cause, whichever occurs first.
Overall survival (OS)
Overall survival defined as the time from the date of randomization to the date of death due to any cause.
PFS per RECIST 1.1 by investigator assessment
Progression Free Survival (PFS) is defined as the time from the date of randomization to the date of the first documentation of objective PD assessed by investigator per RECIST 1.1, or death due to any cause, whichever occurs first.
Objective Response Rate (ORR) by BICR
The proportion of participants who have a confirmed CR or PR, as best overall response assessed by BICR as per RECIST 1.1.
Objective Response Rate (ORR) by investigator
The proportion of participants who have a confirmed CR or PR, as best overall response assessed by investigator as per RECIST 1.1.
Duration of Response (DOR) by BICR
The time from the first documentation of objective response (CR or PR that is subsequently confirmed) to the date of the first documentation of PD as determined by BICR assessment per RECIST 1.1, or death due to any cause, whichever occurs first.