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

NCT ID: NCT06130826

Last Updated: 2025-05-30

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE1

Total Enrollment

24 participants

Study Classification

INTERVENTIONAL

Study Start Date

2025-05-27

Study Completion Date

2026-09-05

Brief Summary

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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

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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

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Breast Carcinoma Colorectal Carcinoma

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Treatment (SBRT, M5A-IL2 ICK)

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.

Group Type EXPERIMENTAL

Biopsy

Intervention Type PROCEDURE

Undergo tissue biopsy

Biospecimen Collection

Intervention Type PROCEDURE

Undergo blood sample collection

Bone Scan

Intervention Type PROCEDURE

Undergo bone scan

Computed Tomography

Intervention Type PROCEDURE

Undergo CT or PET/CT

Immunotherapy

Intervention Type DRUG

Receive M5A-IL2 ICK SC

Magnetic Resonance Imaging

Intervention Type PROCEDURE

Undergo MRI

Positron Emission Tomography

Intervention Type PROCEDURE

Undergo PET/CT

Stereotactic Body Radiation Therapy

Intervention Type RADIATION

Undergo SBRT

Interventions

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Biopsy

Undergo tissue biopsy

Intervention Type PROCEDURE

Biospecimen Collection

Undergo blood sample collection

Intervention Type PROCEDURE

Bone Scan

Undergo bone scan

Intervention Type PROCEDURE

Computed Tomography

Undergo CT or PET/CT

Intervention Type PROCEDURE

Immunotherapy

Receive M5A-IL2 ICK SC

Intervention Type DRUG

Magnetic Resonance Imaging

Undergo MRI

Intervention Type PROCEDURE

Positron Emission Tomography

Undergo PET/CT

Intervention Type PROCEDURE

Stereotactic Body Radiation Therapy

Undergo SBRT

Intervention Type RADIATION

Other Intervention Names

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BIOPSY_TYPE Bx Biological Sample Collection Biospecimen Collected Specimen Collection Bone Scintigraphy CAT CAT Scan Computed Axial Tomography Computerized Axial Tomography Computerized axial tomography (procedure) Computerized Tomography CT CT Scan tomography Immunological Immunological Therapy Immunologically Directed Therapy 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 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 SABR SBRT Stereotactic Ablative Body Radiation Therapy

Eligibility Criteria

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Inclusion Criteria

* 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
* Platelets count \> 100,000/mm\^3
* Aspartate transaminase (AST)/alanine transaminase (ALT) \< 2.5 x upper limit of normal (ULN)
* Bilirubin ≤ ULN
* Patients should have adequate kidney function defined as a serum creatinine \< ULN or calculated creatinine clearance of \> 60ml/min (Cockroft-Gault formula)
* Patients should have adequate cardiac function defined as:

* No history of acute coronary syndromes (including myocardial infarction, unstable angina, Coronary artery bypass grafting (CABG), coronary angioplasty, or stenting) \< 12 months prior to screening
* No impaired cardiovascular function or clinically significant cardiovascular diseases, including any of the following:

* Symptomatic chronic heart failure;
* Evidence of clinically significant cardiac arrhythmias and/or conduction abnormalities
* No uncontrolled arterial hypertension despite appropriate medical therapy (defined as systolic blood pressure \> 160 or diastolic blood pressure \>100)
* Electrocardiogram (EKG) showing normal sinus rhythm and a corrected QT (QTc) ≤ 450 ms for male and ≤ 470 ms for female patients
* Patients should have adequate pulmonary function defined as:

* Lack of uncontrolled pleural effusion requiring recurrent draining procedures (more than once per month)
* Lack of oxygen supplementation dependence
* All subjects must have the ability to understand and the willingness to sign a written informed consent
* Screening 2-dimensional (2-D) echocardiogram (echo) shows a left ventricular ejection fraction (LVEF) \> 40%
* Urinalysis shows lack of proteinuria or a maximum of 1+ proteinuria
* Women of childbearing potential should use highly effective contraception while receiving the trial regimen and for at least 5 half-lives of M5A-IL2 from the last dose of M5A-IL2

Exclusion Criteria

* 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
* Subjects, who in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of the study
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Cancer Institute (NCI)

NIH

Sponsor Role collaborator

City of Hope Medical Center

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Jeffrey Y Wong

Role: PRINCIPAL_INVESTIGATOR

City of Hope Medical Center

Locations

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City of Hope Medical Center

Duarte, California, United States

Site Status RECRUITING

Countries

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United States

Facility Contacts

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Jeffrey Y. Wong

Role: primary

626-256-4673 ext. 95200

Other Identifiers

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NCI-2023-07592

Identifier Type: REGISTRY

Identifier Source: secondary_id

20510

Identifier Type: OTHER

Identifier Source: secondary_id

P30CA033572

Identifier Type: NIH

Identifier Source: secondary_id

View Link

R01CA283603

Identifier Type: NIH

Identifier Source: secondary_id

View Link

20510

Identifier Type: -

Identifier Source: org_study_id

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