A Study to Investigate the Safety, Tolerability, Pharmacokinetics, and Anti-tumor Activity of CBI-1214 T Cell Engager in Participants With Advanced or Metastatic MSS/MSI-L Colorectal Cancer

Official title

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

Overview

This study will investigate the safety, tolerability, pharmacokinetics, and anti-tumor activity of CBI-1214 in participants with advanced or metastatic Microsatellite Stable (MSS)/Microsatellite Instability Low (MSI-L) Colorectal Cancer

Interventions

• Biological CBI-1214
  CBI-1214 is a bispecific T cell engager that binds to LY6G6D and CD3. It is designed to link the patients T cells to cancer cells and to mediate tumor cell killing. LY6G6D is an emerging target specifically expressed on malignant colorectal cancer cells.

Primary outcome measures

• To evaluate the safety and tolerability of CBI-1214 at increasing dose levels and optimized dose levels in participants with advanced or metastatic MSS/MSI-L CRC [Time frame: Approximately 48 months]
• To determine the MTD and/or OBD and select the recommended dose(s) of CBI-1214 for dose optimization [Time frame: Approximately 48 months]

Secondary outcome measures (7)

• To characterize the Serum Concentration of CBI-1214. [Time frame: Approximately 48 months]
• Overall Response Rate (ORR) [Time frame: Approximately 48 months]
• Duration of Response (DOR) [Time frame: Approximately 48 months]
• Progression Free Survival (PFS) [Time frame: Approximately 48 months]
• Time to Response (TTR) [Time frame: Approximately 48 months]
• Clinical Benefit Rate (CBR) [Time frame: Approximately 48 months]
• Overall Survival (OS) [Time frame: Approximately 48 months]

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Sequential

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 10 centers

• Mayo Clinic Arizona — Phoenix
• City of Hope Duarte — Duarte
• UCLA — Los Angeles
• Valkyrie Clinical Trials — Los Angeles
• UCSF — San Francisco
• Mayo Clinic Florida — Jacksonville
• Emory Winship Cancer Institute — Atlanta
• START Midwest — Grand Rapids
• … and 2 more centers

Identifiers

NCT: NCT07321106 · CBI-1214-001

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗