CBI-1214 T-cell engager for advanced MSS/MSI-L colorectal cancer

A Phase 1, First-in-human (FIH), Dose-Escalation and Dose-Optimization Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Anti-tumor Activity of CBI-1214 T Cell Engager in Participants With Advanced or Metastatic Microsatellite Stable (MSS)/Microsatellite Instability Low (MSI-L) Colorectal Cancer

This trial will test whether the experimental T-cell engager CBI-1214 is safe, reaches appropriate blood levels, and can shrink tumors in people with advanced or metastatic MSS/MSI-L colorectal cancer who have had prior treatment.

Quick facts

• Phase: PHASE1
• Study type: Interventional
• Enrollment: 80 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Cartography Biosciences (industry)
• Locations: 4 sites (Los Angeles, California and 3 other locations)
• Trial ID: NCT07321106 on ClinicalTrials.gov

What this trial studies

This first-in-human, phase 1 dose-escalation trial gives increasing doses of CBI-1214 to people with advanced or metastatic MSS/MSI-L colorectal cancer to measure safety, tolerability, pharmacokinetics, and any anti-tumor activity. Eligible participants must have received at least one prior line of standard systemic therapy and provide an archival tumor sample or undergo a fresh biopsy. The trial excludes MSI-High/dMMR tumors and people with certain conditions such as prior solid organ transplant or active interstitial lung disease. Study procedures include regular blood sampling, imaging to track tumor response, and close monitoring for adverse events.

Who should consider this trial

Good fit: Ideal candidates are adults with advanced or metastatic MSS/MSI-L colorectal cancer who have exhausted at least one prior standard systemic therapy and can provide tumor tissue for testing or biopsy.

Not a fit: Patients with MSI-High/dMMR tumors, a history of organ transplant, active interstitial lung disease, or other listed exclusionary conditions are unlikely to be eligible and would not receive benefit from participation.

Why it matters

Potential benefit: If successful, CBI-1214 could offer a new immune-based treatment option for MSS/MSI-L colorectal cancers that often do not respond to current immunotherapies.

How similar studies have performed: T-cell engager therapies have shown promise in some other cancers, but using this specific agent in MSS/MSI-L colorectal cancer is novel and remains largely unproven.

Eligibility criteria

Inclusion Criteria:

The main inclusion criteria include but are not limited to the following:

* Participant with MSS/MSI-L CRC, who has exhausted at least one prior line of standard systemic therapy for their current malignancy.
* Participant with genomic aberrations, including but not limited to BRAFV600E mutations and HER2 amplifications, for which FDA-approved targeted therapies are available, must:

  * Have received prior treatment with applicable FDA-approved targeted therapies AND
  * Either have experienced disease progression, be refractory, or be intolerant to directed molecular therapy.
* Participant able to provide archival tissue sample or fresh biopsy tissue sample

Exclusion Criteria:

The main exclusion criteria include but are not limited to the following:

* Participant whose CRC tumor tissues have been identified as dMMR or MSI-H
* Known history of solid organ or tissue transplant; history of interstitial lung disease or non-infectious pneumonitis.
* Untreated central nervous system (CNS) metastatic disease.
* Active autoimmune disease that has required systemic treatment within the past 2 years (participants with hormone replacement therapy for adequately controlled endocrinopathy are allowed in the study).
* History of recent infection (within 4 weeks of C1D1) considered to be caused by one of the pathogens: HSV1, HSV2, VZV, EBV, CMV, measles, Influenza A, Zika virus, Chikungunya virus, mycoplasma pneumonia, Campylobacter jejuni, or enterovirus D68.
* Known seropositive for human immunodeficiency virus, hepatitis B surface antigen, or antibody to hepatitis C virus with confirmatory testing and requiring anti-viral therapy.
* History of Steven's Johnson's syndrome or toxic epidermal necrolysis syndrome.
* Significant medical comorbidities, including uncontrolled hypertension (diastolic blood pressure \>115 mm Hg), unstable angina, congestive heart failure (greater than New York Heart Association class II), severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia, poorly controlled diabetes, severe chronic pulmonary disease, coronary angioplasty, or myocardial infarction within 6 months prior to screening, or uncontrolled atrial or ventricular cardiac arrhythmias.
* Congenital long QT syndrome or a corrected QT interval (QTc) ≥480 ms at screening (unless secondary to pacemaker or bundle branch block).
* Active second primary malignancy within 3 years of Screening other than non-melanoma skin cancers, nonmetastatic prostate cancer, in situ cervical cancer, or ductal or lobular carcinoma in situ of the breast

Where this trial is running

Los Angeles, California and 3 other locations

• Valkyrie Clinical Trials — Los Angeles, California, United States (RECRUITING)
• START Midwest — Grand Rapids, Michigan, United States (RECRUITING)
• NEXT Oncology — San Antonio, Texas, United States (RECRUITING)
• NEXT Oncology — Fairfax, Virginia, United States (RECRUITING)

Study contacts

• Study coordinator: Study Lead

Conditions: Colorectal Cancer, CRC, Metastatic Colon Cancer, Colon Cancer, Advanced Colorectal Cancer, Oncology, Solid Tumor, Phase 1