Platform Study of Immunotherapy Combinations in Colorectal Cancer Liver Metastases
Overview
- Phase
- Phase 2
- Intervention
- Botensilimab
- Conditions
- Colorectal Cancer Metastatic
- Sponsor
- Weill Medical College of Cornell University
- Enrollment
- 24
- Locations
- 1
- Primary Endpoint
- Mean CD8:Treg ratio, as determined by flow cytometry of tumor tissue, at time of surgical resection in each treatment arm
- Status
- Recruiting
- Last Updated
- last year
Overview
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.
Investigators
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
Arms & Interventions
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.
Intervention: Botensilimab
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.
Intervention: Balstilimab
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.
Intervention: Botensilimab
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.
Intervention: Balstilimab
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.
Intervention: AGEN1423
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.
Intervention: Botensilimab
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.
Intervention: Balstilimab
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.
Intervention: Radiation
Outcomes
Primary Outcomes
Mean CD8:Treg ratio, as determined by flow cytometry of tumor tissue, at time of surgical resection in each treatment arm
Time Frame: At surgical resection
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
Secondary Outcomes
- Radiographic Response Rate Per Arm(90 days following the last dose of study drug)
- 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)
- Number of Participants Per Arm with ctDNA Clearance(90 days following the last dose of study drug)