A Phase 2 Study of the Safety and Efficacy of Neoadjuvant Botensilimab in Combination With Balstilimab in the Treatment of Microsatellite Stable / Mismatch Repair Proficient Early Rectal Cancer (RECTIFY-1)
This is a multi-site, prospective, non-randomized phase 2 study evaluating neoadjuvant botensilimab in combination with balstilimab for patients with microsatellite stable (MSS) / mismatch repair proficient (MMRp) early rectal cancer staged T1-T2 N0 by MRI and considered candidates for surgical resection without standard neoadjuvant therapies. Participants will receive a single IV dose of botensilimab on Day 1 followed by balstilimab IV every 2 weeks for up to 6 months, with tumor response assessments during treatment and follow-up afterward.
• Histologically confirmed diagnosis of early-rectal cancer clinically staged T1-T2 N0 M0 by MRI (American Joint Committee on Cancer (AJCC) staging 8th edition, 2017).
• The tumor must confirmed to be MSS/MMRp by local testing.
• The tumor must be evaluable by endoscopy.
• Voluntarily agree to participate by giving signed, dated, and written informed consent prior to any study-specific procedures.
• Age ≥ 18 years of age. Because no dosing or adverse event data are currently available on the use of botensilimab with balstilimab in participants \< 18 years of age, children are excluded from this study.
• Measurable rectal primary on baseline imaging by MRI. The tumor must be definitively at least T1.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Adequate organ function defined as the following laboratory values within 7 days of Cycle 1 Day 1 (C1D1):
‣ Neutrophils ≥ 1500/μL (Must be stable and off any growth factor within 4 weeks of first study treatment administration).
⁃ Platelets ≥ 50× 103/μL.
⁃ Hemoglobin ≥ 8.0 g/dL (transfusion to achieve this level is not permitted within 2 weeks of first study treatment administration).
⁃ Creatinine clearance ≥ 30 mL/min as measured or calculated per local institutional standards.
⁃ Aspartate aminotransferase/alanine aminotransferase ≤ 1.5 × upper limit of normal (ULN).
⁃ Total bilirubin ≤ 1.5 × ULN (except patients with Gilbert syndrome who must have a total bilirubin level of ≤ 3.0 × ULN).
• All participants must undergo multidisciplinary evaluation by a qualified colorectal surgeon, medical oncologist, and radiation oncologist to discuss treatment options for rectal cancer.
‣ Per the treating surgeon, the patient must be a candidate for both TES and/or TME for rectal cancer.
⁃ Per the treating medical oncologist, the patient must be a candidate for standard chemotherapy for rectal cancer.
⁃ Per the treating radiation oncologist, the patient must be a candidate for standard radiation/chemoradiotherapy for rectal cancer.
• The effects of botensilimab with balstilimab on the developing human fetus are unknown. For this reason, women of child-bearing potential (WOCBP) and men enrolled in this study must agree to use highly effective contraceptive measures (See Section 3.4) starting with the Screening Visit through 90 days after the last dose of study treatment. See section 3.4 for more detailed information on contraception requirements.
• Ability to understand and the willingness to sign a written informed consent document.