Platform Study of Immunotherapy Combinations in Colorectal Cancer Liver Metastases

Program Status

Recruiting

Phase

Phase 2

Prior Immunotherapy Allowed

No

CRC-directed Trial

Yes

Drugs

AGEN1423, Balstilimab, Botensilimab

Tags

MSS/ MMRp

Comments

Only for patients with MSS metastatic colorectal adenocarcinoma with liver metastases who are planning to undergo a surgical resection of their liver metastases.
No prior immunotherapy allowed.

Participants will be randomly assigned to one of these arms

  • Botensilimab and balstilimab
  • Botensilimab, balstilimab, and AGEN1423
  • Botensilimab, balstilimab, and radiation

Botensilimab is a next-generation, Fc-enhanced, CTLA-4 inhibitor, and balstilimab is a PD-1 inhibitor. AGEN1423 is an anti-CD73-TGFβ-trap bifunctional antibody. Agents will be administered before and after surgery.

The combination of Botensilimab and balstilimab has results from expanded phase 1a/1b study, NCT03860272: “The administration of these two immunotherapies resulted in objective response rate (ORR) at 23%, disease control rate at 76%, progression-free survival (PFS) 4.1 months, and the median overall survival has not been reached. (“Response” is a tumor reduction of greater than 30%, with stable disease at +/- 30%). The estimated 12-month overall survival at 63% is better than the current standard of care.

Patients had received a median of four prior lines of therapy, and 59% had RAS mutations. Prior immunotherapy was allowed in this trial.

Most patients (91%) reported immune-related adverse events (irAEs). The most common were diarrhea/colitis (43%) and fatigue (34%). The most common grade 3 irAEs were diarrhea/colitis (20%), fatigue (4%), and pyrexia (raised body temperature) (4%)” See Helpful Links.

Location Location Status
United States
Weill Cornell Medicine/NewYork-Presbyterian Hospital
New York, New York 10065
Recruiting

Contacts

Myriam Elizaire-Williams
Contact
mye4001@med.cornell.edu

Inclusion 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

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

NCT ID

NCT06300463

Date Trial Added

2024-03-08

Updated Date

2024-04-12