Platform Study of Immunotherapy Combinations in Colorectal Cancer Liver Metastases

NCT ID: NCT06300463

Last Updated: 2025-04-06

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 24 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-03-26
• Study Completion Date: 2027-03-31

Brief Summary

The goal of this clinical trial is to to learn about different combinations of immunotherapy in patients with colorectal cancer whose cancer has spread to their liver and are planning to have surgery to remove tumor metastases from their liver. The main questions it aims to answer are:

• whether these combinations of immunotherapy change the tumor microenvironment in the liver
• whether these combinations of immunotherapy are safe and effective when used in colorectal cancer with liver metastases

Participants will be randomly assigned to one of the following:

• Botensilimab and balstilimab
• Botensilimab, balstilimab, and AGEN1423
• Botensilimab, balstilimab, and radiation

Participants will be asked to come in to receive drug infusions (and radiation, if applicable) before and after their surgical resection. Participants will be followed for up to 2 years.

Detailed Description

This is a single-center, 3-arm, randomized, open-label, phase II, screening study to assess the initial immunological changes in the tumor microenvironment in response to treatment with combination immunotherapy (Botensilimab/ Balstilimab), with or without radiation and/or additional TGFβ-CD73 trap, in patients with colorectal cancer liver metastases.

Participants who meet eligibility criteria will be randomized to receive one of 3 investigational treatment: botensilimab + balstilimab (Arm 1); botensilimab + balstilimab + AGEN1423 (Arm 2); or botensilimab + balstilimab + radiation (Arm 3). The study arms are not directly or formally compared with each other. It is established that the tumor infiltrating lymphocytes have been predictive of patient survival following resection of colorectal cancer liver metastases. Immunotherapy combinations with an increase in the ratio of CD8+ T cells: Tregs will be considered for further investigation.

All participants will have a total of four treatment visits to receive immunotherapy infusions. Two visits will occur prior to surgery, each approximately 3 weeks apart. Surgery will be scheduled between day 28-42. After surgery, you will return for two more treatment visits. After the last dose of immunotherapy, participants will come to the clinic approximately 3 weeks and 3 months later for follow-up visits. Participants will be followed remotely for up to two years.

Conditions

Colorectal Cancer Metastatic; Liver Metastases; Colorectal Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Botensilimab and Balstilimab

Two balstilimab infusions will be given prior to surgery and two infusions will be given after surgery, for a total of four doses. Each infusion will be scheduled approximately 3 weeks apart. On the same day as the first and third balstilimab infusions, botensilimab will also be given, for a total of two doses, one before and one after surgery.

Group Type: EXPERIMENTAL

Botensilimab

Intervention Type: DRUG

75 mg IV Q6W

Balstilimab

Intervention Type: DRUG

450 mg IV Q3W

Botensilimab, Balstilimab, and AGEN1423

Two balstilimab infusions will be given prior to surgery and two infusions will be given after surgery, for a total of four doses. On the same day as each balstilimab infusion, participants will also receive AGEN1423 infusions, for a total of four doses. Each infusion will be scheduled approximately 3 weeks apart. On the same day as the first and third balstilimab + AGEN1423 infusions, botensilimab will also be given, for a total of two doses, one before and one after surgery.

Group Type: EXPERIMENTAL

Botensilimab

Intervention Type: DRUG

75 mg IV Q6W

Balstilimab

Intervention Type: DRUG

450 mg IV Q3W

AGEN1423

Intervention Type: DRUG

30 mg/kg IV Q3W

Botensilimab, Balstilimab, and Radiation

Participants will receive 3 doses of radiation prior to surgery. Additionally, two balstilimab infusions will be given prior to surgery and two infusions will be given after surgery, for a total of four doses. Each infusion will be scheduled approximately 3 weeks apart. On the same day as the first and third balstilimab infusions, botensilimab will also be given, for a total of two doses, one before and one after surgery.

Group Type: EXPERIMENTAL

Botensilimab

Intervention Type: DRUG

75 mg IV Q6W

Balstilimab

Intervention Type: DRUG

450 mg IV Q3W

Radiation

Intervention Type: RADIATION

8Gy x 3 between Day 0 - 18; Allowed techniques for radiation are 3D conformal, intensity modulated radiotherapy (IMRT), or SBRT

Interventions

Botensilimab

75 mg IV Q6W

Intervention Type: DRUG

Balstilimab

450 mg IV Q3W

Intervention Type: DRUG

AGEN1423

30 mg/kg IV Q3W

Intervention Type: DRUG

Radiation

8Gy x 3 between Day 0 - 18; Allowed techniques for radiation are 3D conformal, intensity modulated radiotherapy (IMRT), or SBRT

Intervention Type: RADIATION

Other Intervention Names

AGEN1181; AGEN2034

Eligibility Criteria

Inclusion Criteria

• Diagnosis of metastatic colorectal adenocarcinoma with liver metastases
• Participant must be planning to undergo a surgical resection of their liver metastases.
• Tumor is non-MSI-H/dMMR
• Presence of measurable disease
• Participants must be willing to consent to additional molecular analyses of tumor samples removed during surgery for research purposes
• Women of childbearing potential (WOCBP), or anyone with a uterus, must not be pregnant or breastfeeding. All participants of childbearing potential must agree to use highly effective contraception during this study
• Participants may not receive chemotherapy, growth factor support, transfusions, or albumin administration within 14 days of start of study treatment.

Exclusion Criteria

• Not eligible for surgery
• Any medical condition such as uncontrolled infection, uncontrolled diabetes mellitus or cardiac disease which, in the opinion of the treating physician, would make this protocol unreasonably hazardous for the patient.
• Previous allogeneic tissue/organ transplant
• Previously received PD-1, PD-L1, or CTLA-4 therapy including experimental immunologic agents
• Participants must not have any contraindications to immune checkpoint inhibitors
• Participants must not have active autoimmune disease that has required systemic treatment within 2 years prior to registration. Some exceptions are allowed

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Agenus Inc.

INDUSTRY

Sponsor Role: collaborator

Weill Medical College of Cornell University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Manish Shah, M.D.

Role: PRINCIPAL_INVESTIGATOR

Weill Medical College of Cornell University

Locations

Weill Cornell Medicine/NewYork-Presbyterian Hospital

New York, New York, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Casey Owens

Role: CONTACT

cdo4001@med.cornell.edu

646-962-6046

Myriam Elizaire-Williams

Role: CONTACT

mye4001@med.cornell.edu

Facility Contacts

Casey Owens

Role: primary

cdo4001@med.cornell.edu

646-962-6046

Myriam Elizaire-Williams

Role: backup

mye4001@med.cornell.edu

Other Identifiers

23-06026214

Identifier Type: -

Identifier Source: org_study_id