Phase II Study of Adjuvant Botensilimab in Combination With Balstilimab in Patients With Colorectal Cancer and Persistent Circulating Tumor DNA Following Surgery and Chemotherapy
The researchers are doing this study to find out whether the combination of botensilimab and balstilimab (BOT/BAL), followed by balstilimab alone, is an effective treatment for people with microsatellite stable (MSS) colorectal cancer or colorectal liver metastases (CRLM) who have measurable residual disease (MRD) after standard treatment with surgery and chemotherapy or total neoadjuvant therapy (TNT).
• Subject or legally authorized representative, is willing and able to provide written informed consent.
• Histologically- or cytologically- confirmed colorectal cancer.
• ≥ 18 years of age on day of signing informed consent.
• Consent for use of archival tissue and blood draws for research purposes.
• Performance status of ECOG 0 or 1.
• Known non-MSI-H/pMMR by IHC, PCR or NGS testing. MSKCC confirmation of non-MSI-H/pMMR status is not mandatory prior to enrollment and treatment on the study. For patients with outside testing, if sufficient tissue is available testing may be repeated at MSKCC and will not impact initial eligibility.
• Consent to undergo MSK IMPACT or NGS, if not previously done
• Disease specific criteria:
∙ Cohorts 1a and 2a: Undergone a complete surgical resection (R0) for stage III colon or rectal cancer, followed by adjuvant chemotherapy with FOLFOX or CAPEOX. Post-operative chemotherapy not required if received previous oxaliplatin-based therapy. Total Neoadjuvant Therapy for rectal cancer with complete clinical and radiographic response is allowed.
‣ Cohorts 1b and 2b: Undergone a complete surgical resection (R0) for liver metastasis (ablation or stereotactic body radiation therapy \[SBRT\], but not Y-90, is permitted) and completed standard peri-operative chemotherapy. Peri-operative chemotherapy not required if received previous oxaliplatin-based therapy. Prior floxuridine via Hepatic Arterial Infusion Pump is permitted. Completed definitive treatment for the primary tumor including (R0) resection, or Total Neoadjuvant Therapy for rectal cancer with complete clinical and radiographic response.
• Positive ctDNA following completion of appropriate standard of care therapy.
• Patients must sign informed consent within 6 weeks of positive ctDNA result. The 6 weeks is considered from the date that the ctDNA is resulted, and not the date it is drawn.
• Adequate organ function, defined as:
⁃ Absolute Neutrophil Count ≥ 1,500/mm3.
⁃ Platelet count ≥ 75,000/mm3.
⁃ Hemoglobin ≥ 9.0 g/dL
⁃ Creatinine clearance (CrCl) ≥60 mL/min.
⁃ AST and ALT ≤ 2.5 × ULN
⁃ Bilirubin ≤ 1.5 × ULN or Direct bilirubin ≤ ULN
∙ Subjects of childbearing potential (or with partners of childbearing potential) must use effective contraception for the course of the study starting with the screening visit through at least 5 months after the last dose of study treatment. Appropriate methods of birth control include abstinence, oral contraceptives, implantable hormonal contraceptives, or double barrier method (diaphragm plus condom).