NCT06130826

Immune Response Activation for the Treatment of Unresectable Metastatic Colorectal Cancer or CEA Positive Metastatic Breast Cancer

A Phase I Study of M5A-IL2 Immunocytokine Combined With Stereotactic Body Radiation Therapy (SBRT) in Patients With Metastatic Colorectal Cancer or CEA-Positive Metastatic Breast Cancer

• Status: Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 24 (estimated)
• Sponsor: City of Hope Medical Center · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This phase I trial studies the side effects and best dose of M5A-IL2 immunocytokine (M5A-ICK) combined with stereotactic body radiation therapy (SBRT) and to see how well they work in treating patients with colorectal cancer or xarcinoembryonic antigen (CEA) positive breast cancer that cannot be removed by surgery (unresectable) or has spread from where it first started (primary site) to other places in the body (metastatic). Carcinoembryonic Antigen (CEA) is a protein that is present in most colorectal cancers and in many other cancers, such as breast cancer, as well. SBRT uses special equipment to position a patient and deliver radiation to tumors with high precision. This method may kill tumor cells with fewer doses over a shorter period and cause less damage to normal tissue. Cytokines are signaling proteins that help control inflammation in the body. They allow the immune system to mount a defense if germs or cancer or other substances that can make people sick enter the body. Interleukin-2 (IL-2) is a powerful cytokine able to regulate the immune responses that are important for anticancer immunity. Immunocytokines (also called antibody-cytokine fusion proteins) are small proteins that regulate the activity of immune cells. The M5A-IL2 immunocytokine (M5A-ICK) combines the cancer targeting features of the M5A antibody with the immune system regulation properties of the cytokine IL-2. Giving M5A-ICK in combination with standard of care (SOC) SBRT may work better in treating patients with unresectable metastatic colorectal cancer or CEA positive metastatic breast cancer.

Detailed description

PRIMARY OBJECTIVE: I. Identify the maximum tolerated dose (MTD) and recommend phase 2 dose (RP2D) and characterize toxicities associated with administration of the M5A-IL2 after fractionated SBRT. SECONDARY OBJECTIVES: I. Describe the therapeutic response to treatment of irradiated and unirradiated tumors per Criteria in Solid Tumors version 1.1 (RECIST v 1.1) guidelines. II. Describe AEs by M5A-IL2 dose level, per Common Terminology Criteria for Adverse Events \[CTCAE\] version 5.0. III. Describe the pharmacokinetics of M5A-IL2. IV. Describe the frequency of auto-antibody formation, overall and by dose of M5A-IL2. EXPLORATORY OBJECTIVE: I. If medically feasible, tumors targeted for SBRT will be biopsied pre-SBRT and 1-2 weeks post 3rd dose of M5A-IL2. OUTLINE: This is a dose-escalation study of M5A-ICK. Patients undergo SOC SBRT over 3 fractions on days 1, 3, and 5, followed by M5A-ICK subcutaneously (SC) on days 8, 9, and 10 once daily for a single cycle on study. Patients undergo computed tomography (CT) or positron emission tomography (PET)/CT as well as blood sample collection throughout the trial. Patients may undergo magnetic resonance imaging or bone scan as clinically indicated on the trial. Additionally, patients may optionally undergo tissue biopsy during screening and on study. After completion of study treatment, patients are followed-up at 3 months.

Conditions

• Breast Carcinoma
• Colorectal Carcinoma

Interventions

Type	Name	Description
PROCEDURE	Biopsy	Undergo tissue biopsy
PROCEDURE	Biospecimen Collection	Undergo blood sample collection
PROCEDURE	Bone Scan	Undergo bone scan
PROCEDURE	Computed Tomography	Undergo CT or PET/CT
DRUG	Immunotherapy	Receive M5A-IL2 ICK SC
PROCEDURE	Magnetic Resonance Imaging	Undergo MRI
PROCEDURE	Positron Emission Tomography	Undergo PET/CT
RADIATION	Stereotactic Body Radiation Therapy	Undergo SBRT

Timeline

• Start date: 2025-05-27
• Primary completion: 2026-09-05
• Completion: 2026-09-05
• First posted: 2023-11-14
• Last updated: 2025-05-30

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study