BAL/BOT/agenT-797 in pMMR CRC With Liver Metastases

ConditionColorectal Cancer Metastatic

Trial statusRecruiting

Trial phasePhase 2

Trial typeInterventional

Biological sexAll

Age18+

SponsorDarren Sigal, MD

About this trial

The goal of this clinical trial is to learn whether the combination of balstilimab, botensilimab, and agenT-797 is safe and effective in treating adults with previously treated metastatic colorectal cancer that is microsatellite stable (pMMR) and has spread to the liver.

The main questions it aims to answer are:

* What proportion of participants experience tumor shrinkage (objective response rate) based on imaging assessments? * What side effects occur with this combination treatment, including immune-related and cytokine-related reactions?

All participants in this study will receive the combination treatment. There is no comparison group.

Participants will:

* Receive balstilimab, botensilimab, and agenT-797 in repeating 42-day treatment cycles * Undergo imaging scans (such as CT or MRI) to assess tumor response * Have blood samples collected to monitor safety and evaluate biomarkers * Provide tumor tissue samples for research * Be monitored for side effects throughout the study * Participate in follow-up visits to assess survival after treatment completion

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Adults ≥18 years of age with histologically confirmed metastatic colorectal cancer with liver metastases, including evidence of active liver disease if previously treated locally

At least one measurable lesion per RECIST v1.1, with ≥1 target lesion in the liver

Tumor confirmed as microsatellite stable (MSS)/proficient mismatch repair (pMMR) per a FDA-approved assay (Caris MI Cancer Seek®, FoundationOne® CDx, or Tempus xT CDx).

Received ≥1 prior line of systemic therapy including fluorouracil, oxaliplatin, and irinotecan (not necessarily in combination), and prior EGFR inhibitor or bevacizumab if eligible, unless contraindicated

Disqualifiers

Tumor is dMMR/MSI-high

Prior treatment with PD-1, PD-L1, CTLA-4 inhibitors, or other immunotherapy agents

Evidence of bowel obstruction, impending obstruction, or recent obstruction (within 3 months)

Refractory ascites requiring frequent paracentesis or recent escalation of diuretics

Trial design

Design model

Single group

Treatments tested in this trial

Balstilimab (BAL)
Drug
Administered at a fixed dose of 240mg intravenously (IV) on Days 1, 15, 29 of each 42-day cycle, for up to 9 cycles.
Botensilimab (BOT)
Drug
Administered at a fixed dose of 75mg IV on Day 1 of Cycles 1 through 4. In the event of protocol-defined toxicity, the dose may be reduced to 50mg IV per protocol defined criteria.
agenT-797
Drug
Administered at a dose of 1.4 x 107 cells/kg IV on Day 1 of Cycle 1 and Day 15 of Cycle 2.

Treatment groups

17 Participants

are divided into 1 treatment group

Group A: Treatment armExperimental treatment 3 interventions

Trial outcomes

Primary outcomes

Overall Response Rate (ORR)

ORR, defined as the proportion of participants whose best overall response (BOR) is either Complete Response (CR) or Partial Response (PR) per RECIST v1.1.

Time frame

From enrollment until first documented disease progression or end of study treatment (up to approximately 12 months).

Secondary outcomes

Overall response rate in liver metastasis (ORLM)

ORLM, defined as the proportion of participants whose best overall response (BOR) in liver target lesions is Complete Response (CR-Liver) or Partial Response (PR-Liver) per RECIST v1.1.

Time frame

From enrollment until first documented disease progression or end of study treatment (up to approximately 12 months).

Progression free survival (PFS) at 6 months (PFS6)

Proportion of participants alive and progression-free at 6 months

Time frame

At 6 months from enrollment

Progression Free Survival (PFS) at 12 months (PFS12)

Proportion of participants alive and progression-free at 12 months

Time frame

At 12 months from enrollment

Overall Survival (OS)

Defined as the time interval from date of enrollment to death from any cause.

Time frame

From enrollment until death from any cause

Other outcomes

Changes in circulating tumor DNA (ctDNA) from baseline during study treatment in responders and non-responders, per RECIST1.1.

Absolute and percent change from baseline ctDNA levels at scheduled post-baseline assessments (Cycle 3/Day 1, Cycle 5/Day 1, and End of Treatment).

Time frame

From baseline through post-baseline ctDNA assessments up to End of Treatment (approximately 12 months).

Immunophenotyping and Immune Profiling of Peripheral Blood and Tumor Microenvironment (TME)

Time frame

From baseline through longitudinal immune profiling assessments during study treatment and at End of Treatment (up to approximately 12 months).

Sponsors and contacts

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

Darren Sigal, MD

Lead sponsor

Scripps Health

Sponsor institution

Scripps Health

Collaborator

Source ClinicalTrials.gov

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