Botensilimab Plus Balstilimab and Fasting Mimicking Diet Plus Vitamin C for Patients With KRAS-Mutant Metastatic Colorectal Cancer

Description

PRIMARY OBJECTIVES:

I. To evaluate the feasibility of the fasting mimicking diet (FMD) when combined with vitamin C and botensilimab plus balstilimab by determining the proportion of patients who adhere to the FMD ≥ 75% of the designated days and receive all doses of botensilimab, balstilimab and Vitamin C for at least any two cycles of therapy.

II. To characterize the safety and tolerability of FMD and vitamin C when combined with botensilimab and balstilimab by assessing any grade toxicities per Common Terminology Criteria for Adverse Events (CTCAE) 5.0.

SECONDARY OBJECTIVES:

I. To obtain a preliminary assessment of anti-tumor activity of botensilimab plus balstilimab and FMD plus vitamin C by determining the overall response rate using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.

II. To estimate the progression-free and overall survival in patients with KRAS-mutant colorectal cancer (CRC) receiving botensilimab plus balstilimab and FMD plus vitamin C.

EXPLORATORY OBJECTIVES:

I. To characterize circulating tumor deoxyribonucleic acid (ctDNA) and ctDNA methylation (TET, Wnt, JAK/STAT, PI3K/AKT, CXCR, ALDH, AMPK) profiles at baseline, on treatment and at disease progression.

II. To examine metabolomic markers (IGF-1, GAPDH, DHA, GLUT-1, iron signaling) at baseline, on treatment and at disease progression.

OUTLINE:

Patients receive botensilimab intravenously (IV) over 30 minutes on day 1 of each cycle for up to 4 cycles. Patients receive balstilimab IV over 30 minutes and vitamin C IV over 30 minutes on days 1, 15 and 29 of each cycle. Patients undergo a FMD on days -4 to -1 of each cycle. Cycles repeat every 42 days for up to 2 years in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo blood sample collection, computed tomography (CT) scans and magnetic resonance imaging (MRI) throughout the study.

After completion of study intervention, patients are followed up at 30 days and every 3 months for up to 6 months.