NCT06730100

CBX-12 for the Treatment of Metastatic Chemotherapy-Refractory Microsatellite Stable Colorectal Cancer

Phase 2 Trial of CBX-12 for Metastatic Chemotherapy-Refractory Microsatellite Stable Colorectal Cancer

• Status: Withdrawn
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 0 (actual)
• Sponsor: National Cancer Institute (NCI) · NIH
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This phase II trial studies how well CBX-12 works in treating patients with microsatellite stable colorectal cancer that has spread to other parts of the body (metastatic) and is no longer responding to chemotherapy treatment (chemotherapy-refractory). The usual approach to treating colorectal cancer includes treatment with surgery, radiation, or Food and Drug Administration (FDA)-approved drugs such as trifluridine-tipiracil, bevacizumab, regorafenib, or fruquintinib. However, most metastatic colorectal patients progress through all approved treatments and eventually succumb to their disease. CBX-12 is a drug that contains a peptide (a substance that contains many amino acids \[molecules that join together to form proteins\]) called pHLIP, linked to an anticancer substance called exatecan. Upon administration, pHLIP gets inserted into the cellular membrane of tumor cells, delivering exatecan to kill them. Giving CBX-12 may work better than the usual approach in treating patients with metastatic chemotherapy-refractory microsatellite stable colorectal cancer.

Detailed description

PRIMARY OBJECTIVE: I. To determine the clinical activity, as determined by response rate, of pH low insertion peptide-exatecan conjugate CBX-12 (CBX-12) in microsatellite stable/mismatch repair proficient (MSS/pMMR) metastatic colorectal cancer (mCRC) patients. SECONDARY OBJECTIVES: I. To evaluate the pharmacodynamics of CBX-12 (DDR3 and apoptosis). II. To determine the effect of CBX-12 on progression-free survival (PFS). EXPLORATORY OBJECTIVES: I. To evaluate the tissue and plasma pharmacokinetics (PK) of CBX-12 and free exatecan. II. To evaluate circulating tumor deoxyribonucleic acid (DNA) (ctDNA) as a predictor for treatment response to CBX-12. III. To evaluate the safety and tolerability of CBX-12 dosed every 21 days. IV. To evaluate biomarkers of response to CBX-12 (DNA damage response, apoptosis, SLFN11 expression, TOP1-DNA complex). OUTLINE: Patients receive CXB-12 intravenously (IV) over 60 minutes on day 1 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo x-rays during screening, and computed tomography (CT), magnetic resonance imaging (MRI), and blood collection throughout the study and patients may undergo biopsy during screening and on study. After completion of study treatment, patients are followed up at 30 days and then every 3 months for 12 months or until death.

Conditions

• Metastatic Mismatch Repair Proficient Colorectal Carcinoma
• Refractory Mismatch Repair Proficient Colorectal Carcinoma
• Stage IV Colorectal Cancer AJCC v8

Interventions

Type	Name	Description
PROCEDURE	Biopsy Procedure	Undergo biopsy
PROCEDURE	Biospecimen Collection	Undergo blood sample collection
PROCEDURE	Computed Tomography	Undergo CT scan
PROCEDURE	Magnetic Resonance Imaging	Undergo MRI
DRUG	pH Low Insertion Peptide-exatecan Conjugate CBX-12	Given IV
PROCEDURE	X-Ray Imaging	Undergo chest x-rays

Timeline

• Start date: 2026-02-17
• Primary completion: 2026-12-01
• Completion: 2026-12-01
• First posted: 2024-12-12
• Last updated: 2025-10-06

Locations

15 sites across 1 country: United States

Regulatory

• FDA-regulated drug study