Platform Study of Immunotherapy Combinations in Colorectal Cancer Liver Metastases

NCT06300463 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 23-06026214
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

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.

Conditions

Colorectal Cancer Metastatic; Liver Metastases; Colorectal Cancer

Keywords

Botensilimab; Balstilimab; Immunotherapy

Outcome Measures

Primary Outcomes (1)

• Mean CD8:Treg ratio, as determined by flow cytometry of tumor tissue, at time of surgical resection in each treatment arm

  Preliminary immunological response to treatment will be assessed by comparison of the CD8:Treg ratios in tumor tissue obtained during standard of care surgical resection between treatment arms. CD8:Treg ratio will be assessed by flow cytometry

  At surgical resection

Secondary Outcomes (4)

• Number of Treatment-Related Adverse Events (TRAEs) as assessed by CTCAE v5.0 per treatment arm

  90 days following the last dose of study drug

• Pathological Response Rate Per Arm

  At surgical resection

• Radiographic Response Rate Per Arm

  90 days following the last dose of study drug

• Number of Participants Per Arm with ctDNA Clearance

  90 days following the last dose of study drug

Study Arms (3)

Botensilimab and Balstilimab

EXPERIMENTAL

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.

Drug: Botensilimab; Drug: Balstilimab

Botensilimab, Balstilimab, and AGEN1423

EXPERIMENTAL

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.

Drug: Botensilimab; Drug: Balstilimab; Drug: AGEN1423

Botensilimab, Balstilimab, and Radiation

EXPERIMENTAL

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.

Drug: Botensilimab; Drug: Balstilimab; Radiation: Radiation

Interventions

Botensilimab DRUG

75 mg IV Q6W

Also known as: AGEN1181

Botensilimab and Balstilimab; Botensilimab, Balstilimab, and AGEN1423; Botensilimab, Balstilimab, and Radiation

Balstilimab DRUG

450 mg IV Q3W

Also known as: AGEN2034

Botensilimab and Balstilimab; Botensilimab, Balstilimab, and AGEN1423; Botensilimab, Balstilimab, and Radiation

AGEN1423 DRUG

30 mg/kg IV Q3W

Botensilimab, Balstilimab, and AGEN1423

Radiation RADIATION

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

Botensilimab, Balstilimab, and Radiation

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Weill Medical College of Cornell University: lead
• Agenus Inc.: collaborator

Study Sites (1)

Weill Cornell Medicine/NewYork-Presbyterian Hospital

New York, New York, 10065, United States

RECRUITING

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

balstilimab; Radiation

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Physical Phenomena

Study Officials

• Manish Shah, M.D.

  Weill Medical College of Cornell University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Casey Owens

CONTACT

646-962-6046; cdo4001@med.cornell.edu

Myriam Elizaire-Williams

CONTACT

mye4001@med.cornell.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 29, 2024
• First Posted: March 8, 2024
• Study Start: March 26, 2024
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2027
• Last Updated: May 15, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)