CAR-macrophages for the Treatment of HER2 Overexpressing Solid Tumors

April 10, 2024 updated by: Carisma Therapeutics Inc

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

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

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

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

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

Study Type

Interventional

Enrollment (Estimated)

48

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • United States
    • California
      • Duarte, California, United States, 91010
        • City of Hope National Medical Center
    • North Carolina
      • Chapel Hill, North Carolina, United States, 27599
        • UNC Lineberger Comprehensive Cancer Center
    • Oregon
      • Portland, Oregon, United States, 97239
        • OHSU Knight Cancer Institute
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • Abramson Cancer Center
    • Tennessee
      • Nashville, Tennessee, United States, 37203
        • Tennessee Oncology / Sarah Cannon Research Institute
    • Texas
      • Houston, Texas, United States, 77030
        • M D Anderson Cancer Center
    • Washington
      • Seattle, Washington, United States, 98109
        • Fred Hutchinson Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / 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 total.
Biological: CT-0508
anti-HER2 CAR macrophages
Experimental: 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.
Biological: CT-0508
anti-HER2 CAR macrophages
Experimental: 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).
Biological: CT-0508
anti-HER2 CAR macrophages
Experimental: 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.
Biological: CT-0508
anti-HER2 CAR macrophages
Biological: Pembrolizumab
anti-PD antibody
Other Names:
  • Keytruda

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Assess the safety and tolerability of CT-0508 by estimating the frequency and severity of adverse events in subjects with HER2 overexpressing solid tumors.
Time Frame: 14 months
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.
Time Frame: 12 months
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)
Time Frame: 14 months
Frequency and severity of adverse events including, but not limited to, estimating frequency and severity of Cytokine Release Syndrome (CRS)
14 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Time Frame: 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.
24 months
Estimate progression-free survival (PFS).
Time Frame: 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.
24 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Carisma Therapeutics Inc

Investigators

  • Study Director: Jeanett Wetzel, Carisma Therapeutics

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 2, 2021

Primary Completion (Estimated)

December 31, 2024

Study Completion (Estimated)

December 31, 2024

Study Registration Dates

First Submitted

November 23, 2020

First Submitted That Met QC Criteria

December 3, 2020

First Posted (Actual)

December 9, 2020

Study Record Updates

Last Update Posted (Actual)

April 12, 2024

Last Update Submitted That Met QC Criteria

April 10, 2024

Last Verified

April 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 101 (Hamilton Integrated Research Ethics Board)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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