FOLFOX and Bevacizumab in Combination With Botensilimab and Balstilimab (3B-FOLFOX) for the Treatment of Microsatellite Stable (MSS) Metastatic Colorectal Cancer

Description

PRIMARY OBJECTIVES:

I. To assess the safety and tolerability of leucovorin calcium, fluorouracil, oxaliplatin (FOLFOX) bevacizumab, balstilimab and botensilimab at each dose level in order to inform the recommended phase 2 dose (RP2D). (Phase I) II. To assess the overall response rate of FOLFOX bevacizumab, balstilimab at 240 mg and botensilimab at 25 mg and 75 mg (depending on dose level). (Phase II)

SECONDARY OBJECTIVES:

I. To assess the overall response rate, progression-free survival (PFS), and overall survival (OS) of FOLFOX bevacizumab, balstilimab at 240 mg and botensilimab at 25 mg and 75 mg (depending on dose level). (Phase I) II. To estimate the median PFS and median OS associated with FOLFOX bevacizumab, balstilimab at 240 mg and botensilimab at 25 mg and 75 mg botensilimab (depending on dose level). (Phase II) III. To estimate the duration of response associated with FOLFOX bevacizumab, balstilimab at 240 mg and botensilimab at 25 mg botensilimab and 75 mg (depending on dose level). (Phase II) IV. To evaluate the safety/feasibility of FOLFOX bevacizumab, botensilimab, and balstilimab, through the assessment of adverse events. (Phase II) V. To describe the rate of secondary resection in all arms of treatment and summarize their outcome in terms of disease relapse post-surgery. (Phase II)

CORRELATIVE OBJECTIVE:

I. Evaluate potential circulating biomarkers of response, resistance, activity, and toxicity.

OUTLINE: This is a phase I, dose-escalation study of botensilimab followed by a randomized phase II study.

PHASE I: Patients receive FOLFOX, bevacizumab, balstilimab, and botensilimab intravenously (IV) on study. Patients undergo an x-ray, computed tomography (CT) scan, positron emission tomography (PET) scan, and/or magnetic resonance imaging (MRI) throughout the trial. Patients also undergo blood sample collection during screening and on study.

PHASE II: Patients are randomized to 1 of 2 arms.

ARM I: Patients receive FOLFOX, bevacizumab and balstilimab IV with botensilimab IV at a lower dose on study. Patients undergo an x-ray, CT scan, PET scan, and/or MRI throughout the trial. Patients also undergo blood sample collection during screening and on study.

ARM II: Patients receive FOLFOX, bevacizumab and balstilimab IV with botensilimab IV at a higher dose on study. Patients undergo an x-ray, CT scan, PET scan, and/or MRI throughout the trial. Patients also undergo blood sample collection during screening and on study.