CAR-macrophages for the Treatment of HER2 Overexpressing Solid Tumors

Sponsor

Carisma Therapeutics Inc (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04660929

Collaborator

(none)

Enrollment

Locations

Arm

Anticipated Duration (Months)

3.6

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
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	Biological: CT-0508	Phase 1

Detailed 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

Study Design

Study Type:

Interventional

Anticipated Enrollment :

18 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Feb 2, 2021

Anticipated Primary Completion Date :

Feb 1, 2022

Anticipated Study Completion Date :

Feb 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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.	Biological: CT-0508 anti-HER2 CAR macrophages

Arm

Intervention/Treatment

Experimental: 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.

Biological: CT-0508

anti-HER2 CAR macrophages

Outcome Measures

Primary Outcome Measures

Assess the safety and tolerability of CT-0508 by estimating the frequency and severity of adverse events in subjects with HER2 overexpressing solid tumors. [14 months]
Frequency and severity of adverse events including, but not limited to, estimating frequency and severity of Cytokine Release Syndrome (CRS)
Assess the feasibility of manufacturing CT-0508 by describing the percentage of products passing release criteria. [12 months]
Percentage of products that pass release criteria among all manufactured products.

Secondary Outcome Measures

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]
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.
Estimate progression-free survival (PFS). [24 months]
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	City of Hope National Medical Center	Duarte	California	United States	91010
2	UNC Lineberger Comprehensive Cancer Center	Chapel Hill	North Carolina	United States	27599
3	Abramson Cancer Center	Philadelphia	Pennsylvania	United States	19104
4	Tennessee Oncology / Sarah Cannon Research Institute	Nashville	Tennessee	United States	37203
5	M D Anderson Cancer Center	Houston	Texas	United States	77030