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CAR-macrophages for the Treatment of HER2 Overexpressing Solid Tumors

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04660929
Recruitment Status : Recruiting
First Posted : December 9, 2020
Last Update Posted : December 19, 2022
Sponsor:
Information provided by (Responsible Party):
Carisma Therapeutics Inc

Study Description
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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 Biological: Pembrolizumab 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

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 Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 48 participants
Allocation: Non-Randomized
Intervention Model: Parallel 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 : February 2, 2021
Estimated Primary Completion Date : July 2023
Estimated Study Completion Date : December 2024

Resource links provided by the National Library of Medicine


Arms and Interventions
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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 Name: Keytruda


Outcome Measures
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Primary Outcome Measures :
  1. 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)

  2. 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.

  3. 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)


Secondary Outcome Measures :
  1. 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.

  2. 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.



Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04660929


Contacts
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Contact: Ramona Swaby, MD, Vice President - Clinical Development (610) 427-3494 Ramona.Swaby@carismatx.com

Locations
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United States, California
City of Hope National Medical Center Recruiting
Duarte, California, United States, 91010
Contact: Joanne E Mortimer, MD    626-218-9200    jmortimer@coh.org   
United States, North Carolina
UNC Lineberger Comprehensive Cancer Center Recruiting
Chapel Hill, North Carolina, United States, 27599
Contact: Cheng    919-445-4208    catherine_cheng@med.unc.edu   
United States, Oregon
OHSU Knight Cancer Institute Recruiting
Portland, Oregon, United States, 97239
Contact: Richard Maziarz, MD    503-494-1080    trials@ohsu.edu   
United States, Pennsylvania
Abramson Cancer Center Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Ciminera    215-220-9678    krista.ciminera@pennmedicine.upenn.edu   
United States, Tennessee
Tennessee Oncology / Sarah Cannon Research Institute Recruiting
Nashville, Tennessee, United States, 37203
Contact: AskSarah    615-329-7274      
Principal Investigator: Melissa Johnson, MD         
United States, Texas
M D Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact: Angela Alexander    713-792-9137    Aalexand@mdanderson.org   
United States, Washington
Fred Hutchinson Cancer Center Recruiting
Seattle, Washington, United States, 98109
Contact: SCCA Intake    206-606-1024    hutchdoc@seattlecca.org   
Sponsors and Collaborators
Carisma Therapeutics Inc
Investigators
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Study Director: Ramona Swaby, MD Carisma Therapeutics
More Information
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Additional Information:

Publications:

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Responsible Party: Carisma Therapeutics Inc
ClinicalTrials.gov Identifier: NCT04660929    
Other Study ID Numbers: 101
First Posted: December 9, 2020    Key Record Dates
Last Update Posted: December 19, 2022
Last Verified: December 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Carisma Therapeutics Inc:
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
Additional relevant MeSH terms:
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Carcinoma
Neoplasms
Breast Neoplasms
Lung Neoplasms
Prostatic Neoplasms
Stomach Neoplasms
Head and Neck Neoplasms
Endometrial Neoplasms
Biliary Tract Neoplasms
Bile Duct Neoplasms
Ovarian Neoplasms
Carcinoma, Hepatocellular
Inflammatory Breast Neoplasms
Carcinoma, Squamous Cell
Carcinoma, Small Cell
 Carcinoma, Non-Small-Cell Lung
Carcinoma, Transitional Cell
Small Cell Lung Carcinoma
Carcinoma, Ovarian Epithelial
Carcinoma, Ductal
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms by Site
Breast Diseases
Skin Diseases
Respiratory Tract Neoplasms
Thoracic Neoplasms
Lung Diseases
Respiratory Tract Diseases
Genital Neoplasms, Male