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

NCT06130826 | Recruiting Phase 1 DMC FDA Drug

• 4 other identifiers: 20510NCI-2023-07592P30CA033572R01CA283603
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Breast Carcinoma; Colorectal Carcinoma

Outcome Measures

Primary Outcomes (2)

• Maximum tolerated dose (MTD) of the M5A-IL2 immunocytokine (M5A-ICK)

  Will be assessed following accelerated titration design 3, single patient cohorts will be used with dose doubling between cohorts until either a dose limiting toxicity (DLT) is observed, or 2 patients experience a moderate (grade 2) M5A-ICK related adverse event. At dose level 5, the design reverts to 3 patient cohorts (following the traditional 3+3 design) with 40% increments between dose levels. In the traditional 3+3 design, once 3 patients at a dose level are evaluable, if none has experienced a DLT, the dose can be escalated.

  At the end of cycle 1 (each cycle is 28 days)

• Recommended phase 2 dose

  Will either be the MTD, or below, based on the full consideration of late adverse events, sub-DLT toxicities, clinical activity, and biological correlatives.

  At the end of cycle 1 (each cycle is 28 days)

Secondary Outcomes (4)

• Therapeutic response to treatment

  Up to 2 years

• Incidence of adverse events

  Up to 3 months after last M5A-ICK injection

• Number of participants with treatment-related auto-antibody formation

  Screening, days 8 and 36, and 3 months

• Pharmacokinetics of M5A-IL2 (M5A-ICK blood clearance )

  Pre-injection, approximately 1, 4 and 6 hours post injection on each day, and one sample done 1 and 2 days following the 3rd subcutaneous dose of M5A-IL2

Study Arms (1)

Treatment (SBRT, M5A-IL2 ICK)

EXPERIMENTAL

Patients undergo SOC SBRT over 3 fractions on days 1, 3, and 5, followed by M5A-ICK SC on days 8, 9, and 10 once daily for a single cycle on study. Patients undergo CT or 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.

Procedure: Biopsy; Procedure: Biospecimen Collection; Procedure: Bone Scan; Procedure: Computed Tomography; Drug: Immunotherapy; Procedure: Magnetic Resonance Imaging; Procedure: Positron Emission Tomography; Radiation: Stereotactic Body Radiation Therapy

Interventions

Biopsy PROCEDURE

Undergo tissue biopsy

Also known as: BIOPSY_TYPE, Bx

Treatment (SBRT, M5A-IL2 ICK)

Biospecimen Collection PROCEDURE

Undergo blood sample collection

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

Treatment (SBRT, M5A-IL2 ICK)

Bone Scan PROCEDURE

Undergo bone scan

Also known as: Bone Scintigraphy

Treatment (SBRT, M5A-IL2 ICK)

Computed Tomography PROCEDURE

Undergo CT or PET/CT

Also known as: CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography, Computerized axial tomography (procedure), Computerized Tomography, CT, CT Scan, tomography

Treatment (SBRT, M5A-IL2 ICK)

Immunotherapy DRUG

Receive M5A-IL2 ICK SC

Also known as: Immunological, Immunological Therapy, Immunologically Directed Therapy

Treatment (SBRT, M5A-IL2 ICK)

Magnetic Resonance Imaging PROCEDURE

Undergo MRI

Also known as: Magnetic Resonance, Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan, Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance, MR, MR Imaging, MRI, MRI Scan, NMR Imaging, NMRI, Nuclear Magnetic Resonance Imaging

Treatment (SBRT, M5A-IL2 ICK)

Positron Emission Tomography PROCEDURE

Undergo PET/CT

Also known as: Medical Imaging, Positron Emission Tomography, PET, PET Scan, Positron emission tomography (procedure), Positron Emission Tomography Scan, Positron-Emission Tomography, proton magnetic resonance spectroscopic imaging, PT

Treatment (SBRT, M5A-IL2 ICK)

Stereotactic Body Radiation Therapy RADIATION

Undergo SBRT

Also known as: SABR, SBRT, Stereotactic Ablative Body Radiation Therapy

Treatment (SBRT, M5A-IL2 ICK)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients should have a diagnosis of metastatic colon or rectal or breast cancer that is pathology proven
• Patients should have a CEA producing colorectal cancer or breast cancer defined as a baseline CEA or prior documented CEA level exceeding 5 ng/ml or evidence of CEA staining by Immunohistochemistry (IHC)
• Patients should 18 years of age or older
• Patients are willing and capable to consent to study and to adhere with all elements of the study
• Patients who have failed to respond to standard systemic therapy, or for whom standard or curative systemic therapy does not exist, is not tolerable or was refused
• Patients should be at least 4 weeks from last receipt of a cytotoxic or biological agent prior to start of SBRT, with the exception of mitomycin C which requires a 6-week washout
• Patients should have unresectable disease or not be a candidate for surgical resection
• Patients must have a minimum of 1 and a maximum of 5 separate metastatic lesions planned for SBRT. (Patients may have \> 5 metastatic lesions overall, however only up to 5 lesions will be treated with SBRT.) SBRT sites must be equal to or less than 5 cm in greatest dimension. SBRT treated sites must be measurable per RECIST 1.1 and can include metastatic sites in the lung, liver, or soft tissue. Sites that are intracranial or in the bone are excluded. Sites deemed not appropriate for SBRT by the treating radiation oncologist are also excluded
• Patients should be at least 4 weeks from last radiation therapy prior to starting SBRT
• Patients should be at least 4 weeks from any investigational therapy prior to starting SBRT, with the exception of prior immunotherapy which would require a 3 month washout
• Patients should have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
• Patients should be considered clinically stable with an estimated overall survival of at least 3 months
• Neutrophil count \> 1500/mm\^3
• Lymphocyte count \> 500/mm\^3
• Hemoglobin \> 9 gm/dl

You may not qualify if:

• Patients on immunosuppressive treatments including supra-physiological doses of corticosteroids
• Patients with history of auto-immune disease including history of inflammatory bowel disease
• Patients with active brain metastases
• Patients in the child-bearing ages who refuse to use adequate birth control measures (example: contraceptives, barrier method, or abstinence)
• Lactating females who do not agree to stop breastfeeding
• Known active hepatitis B or C
• Major surgical procedure within 4 weeks prior to SBRT
• Non-healed wound or surgical incisions
• Radiographic evidence of bowel obstruction
• Electrolyte disturbances (sodium, potassium, magnesium, calcium, and phosphorous) that are not correctable to at least CTCAE grade 1 with replacement therapy
• Known hypersensitivity of any of the study drug agents or components
• Patients should not have any uncontrolled illness including ongoing or active infection
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to the study agents
• Pregnant women are excluded from this study because the investigational agents on this study are highly likely to exert teratogenic or abortifacient effects
• Patients with other active malignancies are ineligible for this study

Sponsors & Collaborators

• City of Hope Medical Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

City of Hope Medical Center

Duarte, California, 91010, United States

RECRUITING

MeSH Terms

Conditions

Breast Neoplasms; Colorectal Neoplasms

Interventions

Biopsy; Specimen Handling; Immunotherapy; Adjuvants, Immunologic; Magnetic Resonance Spectroscopy; Radiosurgery

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Cytodiagnosis; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Diagnostic Techniques, Surgical; Surgical Procedures, Operative; Investigative Techniques; Immunomodulation; Biological Therapy; Therapeutics; Immunologic Factors; Physiological Effects of Drugs; Pharmacologic Actions; Chemical Actions and Uses; Spectrum Analysis; Chemistry Techniques, Analytical; Radiotherapy; Stereotaxic Techniques; Neurosurgical Procedures

Study Officials

• Jeffrey Y Wong

  City of Hope Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 20, 2023
• First Posted: November 14, 2023
• Study Start: May 27, 2025
• Primary Completion (Estimated): September 5, 2026
• Study Completion (Estimated): September 5, 2026
• Last Updated: May 30, 2025

Record last verified: 2025-05

Locations

US (1)