CAR-macrophages for the Treatment of HER2 Overexpressing Solid Tumors

Breast Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04660929
• Other study ID #: 101
• Status: Active, not recruiting
• Phase: Phase 1
• Start date: February 2, 2021
• Est. completion date: December 31, 2024

Study information

• Verified date: April 2024
• Source: Carisma Therapeutics Inc
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Description:

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

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 48
• Est. completion date: December 31, 2024
• Est. primary completion date: December 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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:

Exclusion Criteria:

• 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

Related Conditions & MeSH terms

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

Intervention

Biological:
• CT-0508
anti-HER2 CAR macrophages
• Pembrolizumab
anti-PD antibody

Locations

Country	Name	City	State
United States	UNC Lineberger Comprehensive Cancer Center	Chapel Hill	North Carolina
United States	City of Hope National Medical Center	Duarte	California
United States	M D Anderson Cancer Center	Houston	Texas
United States	Tennessee Oncology / Sarah Cannon Research Institute	Nashville	Tennessee
United States	Abramson Cancer Center	Philadelphia	Pennsylvania
United States	OHSU Knight Cancer Institute	Portland	Oregon
United States	Fred Hutchinson Cancer Center	Seattle	Washington

Sponsors (1)

Lead Sponsor	Collaborator
Carisma Therapeutics Inc

Country where clinical trial is conducted

United States, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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	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.	Proportion of subjects with an objective response (either a complete response [CR] or partial response [PR]) in subjects who received at least 1 dose of CT-0508 and at least the 8-week tumor evaluation as determined by the investigator using RECIST v1.1.	24 months
Secondary	Estimate progression-free survival (PFS).	Defined as the time between the date of first dose and the date of first documented disease progression as determined by the investigator using RECIST v1.1 or death due to any cause, whichever occurs first.; Defined as the time between the date of first dose and the date of first documented disease progression as determined by the investigator using RECIST v1.1 or death due to any cause, whichever occurs first.	24 months

External Links

•   Carisma Therapeutics Clinical Trial website