A Phase II Study of Neoadjuvant Botensilimab and Balstilimab Immunotherapy for Mismatch Repair Proficient Rectal Adenocarcinoma
Overview
- Phase
- Phase 2
- Status
- Recruiting
- Enrollment
- 40
- Locations
- 7
- Primary Endpoint
- Best Overall Response Rate
Overview
Brief Summary
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.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Willing and able to provide written informed consent for trial.
- •a. If participant is unable to provide written informed consent, the legally authorized representative (LAR) of the person who is being asked to participate in this research study may give consent on the participant's behalf.
- •Be ≥18 years of age on the date of signing informed consent.
- •ECOG performance status of 0 or
- •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/
- •No evidence of distant metastases
- •Radiologically measurable or clinically evaluable disease per Protocol Section 13.
- •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.
Exclusion Criteria
- •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 interstitial lung diseases/pneumonitis
- •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.
Arms & Interventions
Participants with locally advanced rectal cancer
Up to 40 patients with mismatch repair proficient (MMRp)/microsatellite stable (MSS) locally advanced (stage II or III) rectal cancer
Intervention: Balstilimab (Drug)
Participants with locally advanced rectal cancer
Up to 40 patients with mismatch repair proficient (MMRp)/microsatellite stable (MSS) locally advanced (stage II or III) rectal cancer
Intervention: Botensilimab (Drug)
Outcomes
Primary Outcomes
Best Overall Response Rate
Time Frame: 1 year
The primary objective of this study is to determine the best overall response rate (ORR) after initial neoadjuvant combination botensilimab and balstilimab in subjects with MMRp/MSS locally advanced (stage II or III) rectal adenocarcinoma. ORR is defined by rectal MRI and endoscopic exam and graded as progressive disease (PD), stable disease (SD) (sustained for 3 months), partial response (PR), near complete response (nCR) and clinical complete response (cCR). Patients with PR, nCR, or cCR will be considered responders, while the rest will be non-responders.
Secondary Outcomes
No secondary outcomes reported