Platform Study of Immunotherapy Combinations in Colorectal Cancer Liver Metastases

Colorectal Cancer Clinical Trial

Official title:

Platform Study of Immunotherapy Combinations in Colorectal Cancer Liver Metastases

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06300463
• Other study ID #: 23-06026214
• Status: Recruiting
• Phase: Phase 2
• Start date: March 26, 2024
• Est. completion date: March 2027

Study information

• Verified date: April 2024
• Source: Weill Medical College of Cornell University
• Contact: Casey Owens
• Phone: 646-962-8189
• Email: cdo4001[@]med.cornell.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 24
• Est. completion date: March 2027
• Est. primary completion date: September 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Colorectal Cancer
• Colorectal Cancer Metastatic
• Colorectal Neoplasms
• Liver Metastases
• Liver Neoplasms
• Neoplasm Metastasis

Intervention

Drug:
• Botensilimab
75 mg IV Q6W
• Balstilimab
450 mg IV Q3W
• AGEN1423
30 mg/kg IV Q3W

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

Locations

Country	Name	City	State
United States	Weill Cornell Medicine/NewYork-Presbyterian Hospital	New York	New York

Sponsors (2)

Lead Sponsor	Collaborator
Weill Medical College of Cornell University	Agenus Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Number of Treatment-Related Adverse Events (TRAEs) as assessed by CTCAE v5.0 per treatment arm	Potentially treatment-related AEs include any AEs that are assessed as possibly, probably, or definitely related to one of the study interventions. AEs will be reported by CTCAE v5.0 term.	90 days following the last dose of study drug
Secondary	Pathological Response Rate Per Arm	Resected tumors from the liver will be examined in their entirety, and regression of resected tumors was assessed by estimating the percentage of residual viable tumor of the macroscopically identifiable tumor bed, as identified on routine hematoxylin and eosin (H&E) staining. In addition, regression will be classified using the Mandard tumor regression grading system. Major pathologic response (MPR) will be defined as =10% of residual viable tumor cells (or = 90% response). PR will be defined as at least 50% tumor regression. Pathological response rate will be reported as the number of patients with MPR or PR.	At surgical resection
Secondary	Radiographic Response Rate Per Arm	Radiographic response will be evaluated based on Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Radiographic response rate will be reported as the number of patients with CR or PR.	90 days following the last dose of study drug
Secondary	Number of Participants Per Arm with ctDNA Clearance	Circulating tumor DNA (ctDNA) will be assessed at 90 days following the last dose of study drug	90 days following the last dose of study drug