RECTIFY-1: Neoadjuvant Botensilimab + Balstilimab in MSS/pMMR Early Rectal Cancer

NCT07735624 | Not Yet Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 26-298
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 3

Brief Summary

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.

Conditions

Early Rectal Cancer; Stage I Rectal Cancer; Microsatellite Stable Rectal Carcinoma

Keywords

Early rectal cancer; Non-operative management; Microsatellite Stable Rectal Carcinoma; stage I rectal cancer

Outcome Measures

Primary Outcomes (1)

• Complete response (cCR plus nCR with pCR at resection) within 6 months from initiation of therapy or nCR with pathologic complete response (pCR) with TES

  Tumor response will be evaluated by a qualified colorectal surgeon using flexible sigmoidoscopy (or equivalent), with biopsy as clinically indicated, and rectal MRI using standard response criteria. Response categories are clinical complete response, near-complete clinical response, no response, or progression. Participants with near-complete clinical response must have pathologic complete response at TES/local excision to meet the endpoint.

  From baseline to 6 months from initiation of therapy

Secondary Outcomes (6)

• Incidence of treatment-emergent adverse events

  From first treatment through survival follow-up, up to 5 years from initiation of therapy

• Incidence of surgical complications

  From surgery through 90-day safety follow-up

• Organ preservation rate

  From initiation of therapy through post-treatment surgical management decision, approximately 6 months

• 3-year locoregional recurrence rate

  From initiation of therapy to 3 years.

• Disease-free survival

  From initiation of therapy to 3 years.

Study Arms (1)

Botensilimab + Balstilimab

EXPERIMENTAL

Participants receive: * Botensilimab: one IV infusion on Cycle 1 Day 1, over about 30 minutes * Balstilimab: IV infusion every 2 weeks on Day 1 of each treatment cycle, over about 30 minutes, for up to 6 months The protocol specifies: * Botensilimab dose: 75 mg IV once * Balstilimab dose: 240 mg IV every 2 weeks for up to 6 months

Drug: Botensilimab; Drug: Balstilimab

Interventions

Botensilimab DRUG

one IV infusion on Cycle 1 Day 1, over about 30 minutes

Botensilimab + Balstilimab

Balstilimab DRUG

IV infusion every 2 weeks on Day 1 of each treatment cycle, over about 30 minutes, for up to 6 months

Botensilimab + Balstilimab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• Tumor is MSI-H/MMRd per any local testing.
• Known TMB \>20mut/Mb or indication for immune checkpoint inhibitor therapy including hypermutated cancers.
• Received prior anti-CTLA-4 or anti-PD-1/PD-L1 therapy and/or other experimental immunologic agents.
• Partial or complete bowel obstruction within the last 3 months, signs/symptoms of bowel obstruction, or known radiologic evidence of impending obstruction.
• Uncontrolled irritable bowel syndrome with predominant diarrhea (IBS-D) and/or other uncontrolled, chronic diarrhea syndromes.
• Presence of rectal cancer metastases.
• Stigmata of hepatic decompensation including a history of variceal bleeding, a history of ascites related to hepatic cirrhosis, or severe portal hypertension.
• Clinically significant (i.e., active) cardiovascular disease: cerebral vascular accident/stroke or myocardial infarction within 6 months of enrollment, unstable angina, congestive heart failure (New York Heart Association class ≥ III), or serious uncontrolled cardiac arrhythmia requiring medication.
• Concurrent malignancy (present during screening) requiring treatment or history of prior malignancy active within 2 years prior to the first dose of study treatment, i.e., patients with a history of prior malignancy are eligible if treatment was completed at least 2 years before the first dose of study treatment and the patient has no evidence of disease. Patients with history of prior early-stage basal/squamous cell skin cancer, low-risk prostate cancer eligible for active surveillance, or noninvasive or in situ cancers who have undergone definitive treatment at any time are also eligible.
• Treatment with one of the following classes of drugs within the delineated time window prior to C1D1:
• Cytotoxic, targeted therapy or other investigational therapy within 3 weeks.
• Investigational monoclonal antibodies, antibody-drug conjugates, radioimmunoconjugates, or similar therapy, within 4 weeks, or 5 half-lives, whichever is shorter.
• Small molecule/tyrosine kinase inhibitors within 2 weeks or less than 5 circulating half- lives of investigational drug.
• Prior therapy for rectal cancer.
• Prior pelvic radiation therapy.

Sponsors & Collaborators

• Dana-Farber Cancer Institute: lead
• Agenus Inc.: collaborator
• Gateway for Cancer Research: collaborator

Study Sites (3)

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

Beth Israel Deaconess Medical Center (BIDMC)

Boston, Massachusetts, 02215, United States

Location

MeSH Terms

Conditions

Rectal Neoplasms

Interventions

balstilimab

Condition Hierarchy (Ancestors)

Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Diseases; Rectal Diseases

Study Officials

• Benjamin Schlecher, MD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Benjamin Schlechter, MD

CONTACT

617-632-4607; benjamin_schlechter@dfci.harvard.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: July 24, 2026
• First Posted: July 30, 2026
• Study Start (Estimated): September 1, 2026
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): December 31, 2032
• Last Updated: July 30, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Data can be shared no earlier than 1 year following the date of publication
• Access Criteria: Contact the Belfer office for Dana -Farber Innovations (BODFI) at innovations@dfci.harvard.edu

Locations

US (3)