RECRUITING

A Study of Botensilimab and Balstilimab for Rectal Adenocarcinoma

Conditions

Microsatellite Stable Rectal Carcinoma Locally Advanced Rectal Adenocarcinoma mismatch repair proficient locally advanced rectal adenocarcinoma microsatellite stable locally advanced rectal adenocarcinoma Memorial Sloan Kettering Cancer Center 24-389

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

The purpose of this study is to find out whether the combination of botensilimab and balstilimab (BOT/BAL) is a safe and effective treatment that causes few or mild side effects for people with mismatch repair proficient (MMRp)/microsatellite stable (MSS) locally advanced rectal adenocarcinoma. The investigators will also find out whether BOT/BAL is an effective treatment when given in combination with standard chemotherapy.

Official Title

A Phase II Study of Neoadjuvant Botensilimab and Balstilimab Immunotherapy for Mismatch Repair Proficient Rectal Adenocarcinoma

Quick Facts

Study Start:2025-02-20

Study Completion:2028-02-20

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT06843434

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
* Willing and able to provide written informed consent for trial. * Be ≥18 years of age on the date of signing informed consent. * ECOG performance status of 0 or 1. * Histologically confirmed rectal adenocarcinoma. * Adenocarcinoma with distal margin of 15 cm or less from the anal verge on endoscopy, staged with endorectal ultrasound (ERUS) or magnetic resonance imaging (MRI) as cT3/cT4 N0 or cT(any) cN1/2. * No evidence of distant metastases * Radiologically measurable or clinically evaluable disease per Protocol Section 13.0. * Tumor specimen that demonstrates intact mismatch repair enzymes by immunohistochemistry or microsatellite stability as demonstrated by NGS or PCR. * Negative pregnancy test done within 14 days prior to beginning treatment, for women of childbearing potential only. Subjects of childbearing potential must be willing to use an adequate method of contraception. Appropriate methods of birth control include abstinence, oral contraceptives, implantable hormonal contraceptives, or double barrier method (diaphragm plus condom). Contraception is required for the course of the study starting with the first dose of study medication through 150 days after the last dose of study medication. Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject. * Nonchildbearing potential is defined as follows (by other than medical reasons): 1. ≥45 years of age and has not had menses for \>1 year 2. Patients who have been amenorrhoeic for \<2 years without history of a hysterectomy and oophorectomy must have a follicle stimulating hormone value in the postmenopausal range upon screening evaluation 3. Post-hysterectomy, post-bilateral oophorectomy, or post-tubal ligation. Documented hysterectomy or oophorectomy must be confirmed with medical records of the actual procedure or confirmed by an ultrasound. Tubal ligation must be confirmed with medical records of the actual procedure, otherwise the patient must be willing to use 2 adequate barrier methods throughout the study. * Demonstrate adequate organ function as defined in the Table 6-1 below within 14 days of Cycle 1 Day 1, and all screening labs should be performed within 14 days of treatment initiation.	* Recurrent rectal cancer. * Prior pelvic radiation therapy, chemotherapy, or surgery for rectal cancer. * Tumor is causing symptomatic bowel obstruction (patients who have a temporary diverting ostomy are eligible). * Other invasive malignancy ≤ 2 years prior to registration. Exceptions are non-melanoma skin cancer that has undergone potentially curative therapy and in situ cervical carcinoma. * Active infection requiring systemic therapy. * Other anticancer or experimental therapy. No other experimental therapies (including chemotherapy, radiation, hormonal treatment, antibody therapy, immunotherapy, gene therapy, vaccine therapy, angiogenesis inhibitors, matrix metalloprotease inhibitors, thalidomide, anti-VEGF/Flk-1 monoclonal antibody or other experimental drugs) of any kind are permitted while the patient is receiving study treatment. * Known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies) * Known active hepatitis B (e.g., HbsAg reactive) or hepatitis C (e.g., HCV RNA \[qualitative\] is detected). * Live vaccination within 28 days prior to receiving the first dose of immunotherapy. The use of inactivated seasonal influenza vaccines (e.g., Fluzone®) will be permitted on study without restriction. * Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine or booster \< 7 days before C1D1. For vaccines requiring more than 1 dose, the full series should be completed prior to C1D1, when feasible. Booster shot not required but also must be administered \> 7 days from C1D1 or \> 7 days from future cycle on study * Clinically significant (i.e., active) cardiovascular disease: cerebral vascular accident/stroke or myocardial infarction within 180 days of enrollment, unstable angina, congestive heart failure (New York Heart Association class ≥ III), or serious uncontrolled cardiac arrhythmia requiring medication. * Known active tuberculosis. * Receiving systemic corticosteroid therapy 1 week prior to the first dose of study drug or receiving any other form of systemic immunosuppressive medication. * Has ongoing or recent (within 5 years) evidence of significant autoimmune disease or any other condition that required treatment with systemic immunosuppressive treatments. The following are not exclusionary: vitiligo, childhood asthma that has resolved, endocrinopathies (such as hypothyroidism or type 1 diabetes) that require only hormone replacement. * Prior allogeneic tissue/solid organ transplant, except for corneal transplants.

Inclusion Criteria

Exclusion Criteria

* Willing and able to provide written informed consent for trial.
* Be ≥18 years of age on the date of signing informed consent.
* ECOG performance status of 0 or 1.
* Histologically confirmed rectal adenocarcinoma.
* Adenocarcinoma with distal margin of 15 cm or less from the anal verge on endoscopy, staged with endorectal ultrasound (ERUS) or magnetic resonance imaging (MRI) as cT3/cT4 N0 or cT(any) cN1/2.
* No evidence of distant metastases
* Radiologically measurable or clinically evaluable disease per Protocol Section 13.0.
* Tumor specimen that demonstrates intact mismatch repair enzymes by immunohistochemistry or microsatellite stability as demonstrated by NGS or PCR.
* Negative pregnancy test done within 14 days prior to beginning treatment, for women of childbearing potential only. Subjects of childbearing potential must be willing to use an adequate method of contraception. Appropriate methods of birth control include abstinence, oral contraceptives, implantable hormonal contraceptives, or double barrier method (diaphragm plus condom). Contraception is required for the course of the study starting with the first dose of study medication through 150 days after the last dose of study medication. Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject.
* Nonchildbearing potential is defined as follows (by other than medical reasons):
1. ≥45 years of age and has not had menses for \>1 year
2. Patients who have been amenorrhoeic for \<2 years without history of a hysterectomy and oophorectomy must have a follicle stimulating hormone value in the postmenopausal range upon screening evaluation
3. Post-hysterectomy, post-bilateral oophorectomy, or post-tubal ligation. Documented hysterectomy or oophorectomy must be confirmed with medical records of the actual procedure or confirmed by an ultrasound. Tubal ligation must be confirmed with medical records of the actual procedure, otherwise the patient must be willing to use 2 adequate barrier methods throughout the study.
* Demonstrate adequate organ function as defined in the Table 6-1 below within 14 days of Cycle 1 Day 1, and all screening labs should be performed within 14 days of treatment initiation.

* Recurrent rectal cancer.
* Prior pelvic radiation therapy, chemotherapy, or surgery for rectal cancer.
* Tumor is causing symptomatic bowel obstruction (patients who have a temporary diverting ostomy are eligible).
* Other invasive malignancy ≤ 2 years prior to registration. Exceptions are non-melanoma skin cancer that has undergone potentially curative therapy and in situ cervical carcinoma.
* Active infection requiring systemic therapy.
* Other anticancer or experimental therapy. No other experimental therapies (including chemotherapy, radiation, hormonal treatment, antibody therapy, immunotherapy, gene therapy, vaccine therapy, angiogenesis inhibitors, matrix metalloprotease inhibitors, thalidomide, anti-VEGF/Flk-1 monoclonal antibody or other experimental drugs) of any kind are permitted while the patient is receiving study treatment.
* Known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies)
* Known active hepatitis B (e.g., HbsAg reactive) or hepatitis C (e.g., HCV RNA \[qualitative\] is detected).
* Live vaccination within 28 days prior to receiving the first dose of immunotherapy. The use of inactivated seasonal influenza vaccines (e.g., Fluzone®) will be permitted on study without restriction.
* Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine or booster \< 7 days before C1D1. For vaccines requiring more than 1 dose, the full series should be completed prior to C1D1, when feasible. Booster shot not required but also must be administered \> 7 days from C1D1 or \> 7 days from future cycle on study
* Clinically significant (i.e., active) cardiovascular disease: cerebral vascular accident/stroke or myocardial infarction within 180 days of enrollment, unstable angina, congestive heart failure (New York Heart Association class ≥ III), or serious uncontrolled cardiac arrhythmia requiring medication.
* Known active tuberculosis.
* Receiving systemic corticosteroid therapy 1 week prior to the first dose of study drug or receiving any other form of systemic immunosuppressive medication.
* Has ongoing or recent (within 5 years) evidence of significant autoimmune disease or any other condition that required treatment with systemic immunosuppressive treatments. The following are not exclusionary: vitiligo, childhood asthma that has resolved, endocrinopathies (such as hypothyroidism or type 1 diabetes) that require only hormone replacement.
* Prior allogeneic tissue/solid organ transplant, except for corneal transplants.

Contacts and Locations

Study Contact

Andrea Cercek, MD

CONTACT

646-888-4189

cerceka@mskcc.org

Paul Romesser, MD

CONTACT

646-888-2118

romessep@mskcc.org

Principal Investigator

Andrea Cercek, MD

PRINCIPAL_INVESTIGATOR

Memorial Sloan Kettering Cancer Center

Study Locations (Sites)

Memorial Sloan Kettering Basking Ridge (Limited Protocol Activities)

Basking Ridge, New Jersey, 07920

United States

Memorial Sloan Kettering Monmouth (Limited Protocol Activities)

Middletown, New Jersey, 07748

United States

Memorial Sloan Kettering Bergen (Limited Protocol Activities)

Montvale, New Jersey, 07645

United States

Memorial Sloan Kettering Cancer Center at Suffolk - Commack (Limited Protocol Activities)

Commack, New York, 11725

United States

Memorial Sloan Kettering Westchester (Limited Protocol Activities)

Harrison, New York, 10604

United States

Memorial Sloan Kettering Cancer Center (All Protocol Activities)

New York, New York, 10065

United States

Memorial Sloan Kettering Nassau (Limited Protocol Activities)

Uniondale, New York, 11553

United States

Collaborators and Investigators

Sponsor: Memorial Sloan Kettering Cancer Center

Andrea Cercek, MD, PRINCIPAL_INVESTIGATOR, Memorial Sloan Kettering Cancer Center

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2025-02-20

Study Completion Date2028-02-20

Study Record Updates

Study Start Date2025-02-20

Study Completion Date2028-02-20

Terms related to this study

Keywords Provided by Researchers

Microsatellite Stable Rectal Carcinoma
mismatch repair proficient locally advanced rectal adenocarcinoma
locally advanced rectal adenocarcinoma
microsatellite stable locally advanced rectal adenocarcinoma
Memorial Sloan Kettering Cancer Center
24-389

Additional Relevant MeSH Terms

Microsatellite Stable Rectal Carcinoma
Locally Advanced Rectal Adenocarcinoma