FOLFOX, Botensilimab, and Balstilimab for the Treatment of Localized Rectal Cancer Before Surgery

Description

PRIMARY OBJECTIVE:

I. To determine the complete clinical response rate for patients with localized rectal cancer treated with neoadjuvant FOLFOX + botensilimab + balstilimab (FOLFOX-BB).

SECONDARY OBJECTIVES:

I. To evaluate the safety of FOLFOX-BB in patients with localized rectal cancer treated with neoadjuvant FOLFOX + botensilimab + balstilimab (FOLFOX-BB).

II. To estimate 3 year disease free survival rates in patients treated with FOLFOX-BB.

III. To estimate 3 year pelvic recurrence rates in patients with localized rectal cancer treated with neoadjuvant FOLFOX + botensilimab + balstilimab (FOLFOX-BB).

IV. To estimate the duration of response in patients with localized rectal cancer treated with neoadjuvant FOLFOX + botensilimab + balstilimab (FOLFOX-BB).

V. To evaluate 5 year survival rates in patients in patients with localized rectal cancer treated with neoadjuvant FOLFOX + botensilimab + balstilimab (FOLFOX-BB).

EXPLORATORY OBJECTIVES:

I. To examine changes in tumor microenvironment in response to FOLFOX-BB. II. To assess serial blood biomarkers to identify potential correlations with treatment response and outcomes.

OUTLINE:

Patients receive leucovorin calcium intravenously (IV) over 2 hours, oxaliplatin IV over 2 hours, and fluorouracil IV over 46 hours on day 1 of each cycle. Patients also receive botensilimab IV over 60 minutes on day 1 of cycles 1 and 4 and balstilimab IV over 30 minutes on day 1 of each cycle. Cycles repeat every 14 days for up to 8 cycles in the absence of disease progression or unacceptable toxicity. Patients with complete clinical response may continue to receive balstilimab alone for an additional 12 cycles. Patients without complete clinical response may receive radiation therapy once daily (QD) on weekdays and capecitabine orally (PO) twice daily (BID) concurrently on days of radiation therapy per standard of care. Additionally, patients undergo blood sample collection, biopsy with endoscopy examination (exam), sigmoidoscopy, digital rectal exam, computed tomography (CT) and magnetic resonance imaging (MRI) throughout the study.

After completion of study treatment, patient are followed at 30 and 90 days, then every 3 months within 1 year of start of treatment, followed by every 6 months for up to 2 years.