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Platform Study of Immunotherapy Combinations in Colorectal Cancer Liver Metastases

ConditionsColorectal Cancer MetastaticLiver MetastasesColorectal Cancer
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorWeill Medical College of Cornell University

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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

Disqualifiers

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

Trial design

Design model

Parallel

Treatments tested in this trial

  • Botensilimab

    Drug

    75 mg IV Q6W

  • Balstilimab

    Drug

    450 mg IV Q3W

  • AGEN1423

    Drug

    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

Treatment groups

24 Participants
are divided into 3 treatment groups
Group A: Botensilimab and BalstilimabExperimental treatment 2 interventions
Group B: Botensilimab, Balstilimab, and AGEN1423Experimental treatment 3 interventions
Group C: Botensilimab, Balstilimab, and RadiationExperimental treatment 3 interventions

Trial outcomes

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

Time frame
At surgical resection

Secondary outcomes

1

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.

Time frame
90 days following the last dose of study drug
2

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.

Time frame
At surgical resection
3

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.

Time frame
90 days following the last dose of study drug
4

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

Time frame
90 days following the last dose of study drug

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Weill Medical College of Cornell University

Lead sponsor

Agenus Inc.

Collaborator

Source ClinicalTrials.gov
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