CAR-macrophages for the Treatment of HER2 Overexpressing Solid Tumors

NCT04660929 | Active Not Recruiting Phase 1 FDA Drug

• 1 other identifier: 101
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 7

Brief Summary

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

Conditions

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

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

Outcome Measures

Primary Outcomes (3)

• Assess the safety and tolerability of CT-0508 by estimating the frequency and severity of adverse events in subjects with HER2 overexpressing solid tumors.

  Frequency and severity of adverse events including, but not limited to, estimating frequency and severity of Cytokine Release Syndrome (CRS)

  14 months

• Assess the feasibility of manufacturing CT-0508 by describing the percentage of products passing release criteria.

  Percentage of products that pass release criteria among all manufactured products.

  12 months

• Assess the safety and tolerability of CT-0508 in combination with pembrolizumab by estimating the frequency and severity of adverse events in subjects with HER2 overexpressing solid tumors (CT-0508 and pembrolizumab substudy only)

  Frequency and severity of adverse events including, but not limited to, estimating frequency and severity of Cytokine Release Syndrome (CRS)

  14 months

Secondary Outcomes (2)

• Estimate the objective response rate (ORR), according to RECIST v1.1, of at least 1 dose of CT-0508 among subjects with HER2 overexpressing solid tumors.

  24 months

• Estimate progression-free survival (PFS).

  24 months

Study Arms (4)

Group 1 and Group 2

EXPERIMENTAL

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.

Biological: CT-0508

Intraperitoneal Administration

EXPERIMENTAL

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.

Biological: CT-0508

89[Zr]radiolabeled CT-0508

EXPERIMENTAL

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).

Biological: CT-0508

CT-0508 in Combination with Pembrolizumab

EXPERIMENTAL

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.

Biological: CT-0508; Biological: Pembrolizumab

Interventions

CT-0508 BIOLOGICAL

anti-HER2 CAR macrophages

89[Zr]radiolabeled CT-0508; CT-0508 in Combination with Pembrolizumab; Group 1 and Group 2; Intraperitoneal Administration

Pembrolizumab BIOLOGICAL

anti-PD antibody

Also known as: Keytruda

CT-0508 in Combination with Pembrolizumab

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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)
• 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

Sponsors & Collaborators

• Carisma Therapeutics Inc: lead

Study Sites (7)

City of Hope National Medical Center

Duarte, California, 91010, United States

Location

UNC Lineberger Comprehensive Cancer Center

Chapel Hill, North Carolina, 27599, United States

Location

OHSU Knight Cancer Institute

Portland, Oregon, 97239, United States

Location

Abramson Cancer Center

Philadelphia, Pennsylvania, 19104, United States

Location

Tennessee Oncology / Sarah Cannon Research Institute

Nashville, Tennessee, 37203, United States

Location

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Fred Hutchinson Cancer Center

Seattle, Washington, 98109, United States

Location

Related Publications (3)

• 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.

  PMID: 32361713 BACKGROUND

• 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.

  PMID: 39920391 DERIVED

• 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.

  PMID: 36441083 DERIVED

MeSH Terms

Conditions

Adenocarcinoma; Bile Duct Neoplasms; Biliary Tract Neoplasms; Urinary Bladder Neoplasms; Breast Neoplasms; Carcinoma, Ductal; Carcinoma, Hepatocellular; Neoplasms; Carcinoma, Non-Small-Cell Lung; Carcinoma, Ovarian Epithelial; Carcinoma, Small Cell; Carcinoma, Squamous Cell; Carcinoma, Transitional Cell; Colorectal Neoplasms; Inflammatory Breast Neoplasms; Stomach Neoplasms; Ovarian Neoplasms; Pancreatic Neoplasms; Prostatic Neoplasms; Head and Neck Neoplasms; Endometrial Neoplasms; Small Cell Lung Carcinoma; Neoplasm Metastasis

Interventions

pembrolizumab

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Digestive System Neoplasms; Neoplasms by Site; Bile Duct Diseases; Biliary Tract Diseases; Digestive System Diseases; Urologic Neoplasms; Urogenital Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urinary Bladder Diseases; Urologic Diseases; Male Urogenital Diseases; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Neoplasms, Ductal, Lobular, and Medullary; Liver Neoplasms; Liver Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases; Endocrine Gland Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Genital Neoplasms, Female; Genital Diseases; Endocrine System Diseases; Gonadal Disorders; Neoplasms, Squamous Cell; Intestinal Neoplasms; Gastrointestinal Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Stomach Diseases; Pancreatic Diseases; Genital Neoplasms, Male; Genital Diseases, Male; Prostatic Diseases; Uterine Neoplasms; Uterine Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Jeanett Wetzel

  Carisma Therapeutics

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 23, 2020
• First Posted: December 9, 2020
• Study Start: February 2, 2021
• Primary Completion: December 31, 2024
• Study Completion: December 31, 2024
• Last Updated: December 18, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (7)