CAR-macrophages for the Treatment of HER2 Overexpressing Solid Tumors

NCT ID: NCT04660929

Last Updated: 2024-12-18

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

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE1

Total Enrollment

48 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-02-02

Study Completion Date

2024-12-31

Brief Summary

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Phase 1, first-in-human, open label study of CAR macrophages in HER2 overexpressing solid tumors.

Detailed Description

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A Phase 1, First in Human Study of Adenovirally Transduced Autologous Macrophages Engineered to Contain an Anti-HER2 Chimeric Antigen Receptor in Subjects with HER2 Overexpressing Solid Tumors

Main Study - Group 1 and Group 2 all HER2 overexpressing solid tumors

Intraperitoneal Substudy - HER2 overexpressing peritoneal disease

89\[Zr\] radiolabeled CT-0508 Substudy - All HER2 overexpressing solid tumors (Univ of Penn, Abramson Cancer Center only)

CT-0508 Combination with Pembrolizumab Substudy - All HER2 overexpressing solid tumors

Conditions

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HER2-positive Adenocarcinoma Bile Duct Cancer Biliary Tract Cancer Bladder Cancer Breast Cancer Breast Neoplasm Carcinoma, Ductal Carcinoma, Hepatocellular Cancer Lung Cancer, Non-Small-Cell Carcinoma, Ovarian Epithelial Carcinoma, Small Cell Carcinoma, Squamous Carcinoma, Transitional Cell Colorectal Cancer Esophagogastric Junction Neoplasms Inflammatory Breast Cancer Stomach Neoplasms Malignant Neoplasms Ovarian Neoplasms Pancreatic Cancer HER2-positive Solid Tumors HER2-positive Breast Cancer HER2-positive Gastric Cancer HER-2 Protein Overexpression HER-2 Gene Amplification Prostate Cancer Head and Neck Cancer Endometrial Cancer Lung Cancer, Small Cell

Keywords

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HER2-positive solid tumors Phase 1 cell therapy CAR-macrophage immunotherapy advanced cancer post menopausal premenopausal metastatic cancer Prostate Cancer Head and Neck Cancer Lung Cancer, Small Cell Endometrial Cancer Lung Cancer, Non-Small Cell

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Group 1 and Group 2

Both groups will receive the full dose manufactured per patient. Group 1 will undergo intra subject dose escalation of IV administrations of up to 500 million total cells on Day 1, up to 1.5 billion total cells on Day 3, and up to 3.0 billion total cells on Day 5. Group 2 will receive the full dose IV on Day 1 of up to 5 billion cells total.

Group Type EXPERIMENTAL

CT-0508

Intervention Type BIOLOGICAL

anti-HER2 CAR macrophages

Intraperitoneal Administration

All cohorts will receive the full dose manufactured per patient. Cohorts 1-3 will undergo intrasubject dose escalations of IP administration as follows:

Cohort 1 up to 500 million total cells on Day 1, up to 1 billion total cells on Day 3 and up to 1.5 billion total cells on Day 5.

Cohort 2 up to 1.5 billion total cells on Day 1, up to 2 billion total cells on Day 3 and any remaining cells on Day 5.

Cohort 3 up to 2.5 billion total cells on Day 1 and up to 2.5 billion total cells on Day 3.

Cohort 4 will 1 dose on Day 1 of up to 5 billion total cells.

Group Type EXPERIMENTAL

CT-0508

Intervention Type BIOLOGICAL

anti-HER2 CAR macrophages

89[Zr]radiolabeled CT-0508

89\[Zr\] radiolabeled group will receive a full dose IV on Day 1 of up to 500 million total cells of 89\[Zr\] radiolabeled CT-0508 and non-radiolabeled CT-0508 of up to 4.5 billion total cells (Univ of Penn Abramson Cancer Center only).

Group Type EXPERIMENTAL

CT-0508

Intervention Type BIOLOGICAL

anti-HER2 CAR macrophages

CT-0508 in Combination with Pembrolizumab

All regimen levels will receive the full dose manufactured per patient up to 5 billion total cells. Regimen Levels 1 and 2 will undergo intrasubject dose escalations of IV administration as follows:

Regimen Level 1: up to 500 million total cells on Day 1, up to 1.5 billion total cells on Day 3, and up to 3.0 billion total cells on Day 5 plus pembrolizumab 200 mg q3w starting on Day 8.

Regimen Level 2: up to 500 million total cells on Day 1, up to 1.5 billion total cells on Day 3, and up to 3.0 billion total cells on Day 5 plus pembrolizumab 200 mg q3w starting on Day 1.

Regimen Level 3 will receive the full dose IV on Day 1 of up to 5 billion total cells plus pembrolizumab 200 mg q3w starting on Day 1.

Group Type EXPERIMENTAL

CT-0508

Intervention Type BIOLOGICAL

anti-HER2 CAR macrophages

Pembrolizumab

Intervention Type BIOLOGICAL

anti-PD antibody

Interventions

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CT-0508

anti-HER2 CAR macrophages

Intervention Type BIOLOGICAL

Pembrolizumab

anti-PD antibody

Intervention Type BIOLOGICAL

Other Intervention Names

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Keytruda

Eligibility Criteria

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Inclusion Criteria

* HER2-positive recurrent or metastatic solid tumors for which there are no available curative treatment options.

* Breast cancer and gastric/gastroesophageal junction cancers must have failed approved HER2-targeted agents.
* Other HER2-positive tumor types must have failed standard of care therapies, while prior therapy with anti-HER2 drugs is not required.
* Subject must be willing and able to undergo tumor tissue biopsy procedures
* Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
* Subject has adequate bone marrow and organ function

Exclusion Criteria

* HIV, active hepatitis B or hepatitis C infection.
* Diagnosis of immunodeficiency or chronic exposure to systemic corticosteroid therapy or any other form of immunosuppressive therapy
* Untreated or symptomatic central nervous system (CNS) metastases or cytology proven carcinomatous meningitis.

o Subjects with small, asymptomatic CNS metastases that do not require treatment are permitted to enroll.
* Left ventricular ejection fraction (LVEF) \<50% as determined by ECHO or multiple gated acquisition scan (MUGA)

Other protocol-defined Inclusion/Exclusion may apply.

CT-0508 in Combination with Pembrolizumab Substudy Only:


* Subjects with severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients
* Subjects with an active autoimmune disease that has required systemic treatment in past 2 years (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs).
* Subjects who have a history of (non-infectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease
* Subjects who have had an allogeneic tissue/solid organ transplant
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Carisma Therapeutics Inc

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Jeanett Wetzel

Role: STUDY_DIRECTOR

Carisma Therapeutics

Locations

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City of Hope National Medical Center

Duarte, California, United States

Site Status

UNC Lineberger Comprehensive Cancer Center

Chapel Hill, North Carolina, United States

Site Status

OHSU Knight Cancer Institute

Portland, Oregon, United States

Site Status

Abramson Cancer Center

Philadelphia, Pennsylvania, United States

Site Status

Tennessee Oncology / Sarah Cannon Research Institute

Nashville, Tennessee, United States

Site Status

M D Anderson Cancer Center

Houston, Texas, United States

Site Status

Fred Hutchinson Cancer Center

Seattle, Washington, United States

Site Status

Countries

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United States

References

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Klichinsky M, Ruella M, Shestova O, Lu XM, Best A, Zeeman M, Schmierer M, Gabrusiewicz K, Anderson NR, Petty NE, Cummins KD, Shen F, Shan X, Veliz K, Blouch K, Yashiro-Ohtani Y, Kenderian SS, Kim MY, O'Connor RS, Wallace SR, Kozlowski MS, Marchione DM, Shestov M, Garcia BA, June CH, Gill S. Human chimeric antigen receptor macrophages for cancer immunotherapy. Nat Biotechnol. 2020 Aug;38(8):947-953. doi: 10.1038/s41587-020-0462-y. Epub 2020 Mar 23.

Reference Type BACKGROUND
PMID: 32361713 (View on PubMed)

Reiss KA, Angelos MG, Dees EC, Yuan Y, Ueno NT, Pohlmann PR, Johnson ML, Chao J, Shestova O, Serody JS, Schmierer M, Kremp M, Ball M, Qureshi R, Schott BH, Sonawane P, DeLong SC, Christiano M, Swaby RF, Abramson S, Locke K, Barton D, Kennedy E, Gill S, Cushing D, Klichinsky M, Condamine T, Abdou Y. CAR-macrophage therapy for HER2-overexpressing advanced solid tumors: a phase 1 trial. Nat Med. 2025 Apr;31(4):1171-1182. doi: 10.1038/s41591-025-03495-z. Epub 2025 Feb 7.

Reference Type DERIVED
PMID: 39920391 (View on PubMed)

Sly LM, McKay DM. Macrophage immunotherapy: overcoming impediments to realize promise. Trends Immunol. 2022 Dec;43(12):959-968. doi: 10.1016/j.it.2022.10.002. Epub 2022 Oct 29.

Reference Type DERIVED
PMID: 36441083 (View on PubMed)

Other Identifiers

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101

Identifier Type: -

Identifier Source: org_study_id