Clinical trial NCT06300463: Platform Study of Immunotherapy Combinations in Colorectal Cancer Liver Metastases
Official title: Platform Study of Immunotherapy Combinations in Colorectal Cancer Liver Metastases
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Colorectal Cancer Metastatic
Liver Metastases
Colorectal Cancer
Keywords: Botensilimab
Balstilimab
Immunotherapy
Lead sponsor: Weill Medical College of Cornell University
Sponsor class: OTHER
Collaborators: name: Agenus Inc.
First posted: 2024-03-08
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Mean CD8:Treg ratio, as determined by flow cytometry of tumor tissue, at time of surgical resection in each treatment arm
timeFrame: At surgical resection
Secondary outcomes:
measure: Number of Treatment-Related Adverse Events (TRAEs) as assessed by CTCAE v5.0 per treatment arm
timeFrame: 90 days following the last dose of study drug
measure: Pathological Response Rate Per Arm
timeFrame: At surgical resection
measure: Radiographic Response Rate Per Arm
timeFrame: 90 days following the last dose of study drug
measure: Number of Participants Per Arm with ctDNA Clearance
timeFrame: 90 days following the last dose of study drug
Other outcomes:
Locations:
city: New York
country: United States
facility: Weill Cornell Medicine/NewYork-Presbyterian Hospital
state: New York
Study officials:
affiliation: Weill Medical College of Cornell University
name: Manish Shah, M.D.
role: PRINCIPAL_INVESTIGATOR
References: