- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04660929
CAR-macrophages for the Treatment of HER2 Overexpressing Solid Tumors
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 Overview
Status
Conditions
- Adenocarcinoma
- Stomach Neoplasms
- Cancer
- Breast Cancer
- Head and Neck Cancer
- Carcinoma, Hepatocellular
- Colorectal Cancer
- Pancreatic Cancer
- Ovarian Neoplasms
- Carcinoma, Ovarian Epithelial
- Carcinoma, Transitional Cell
- Breast Neoplasm
- Prostate Cancer
- Bile Duct Cancer
- Bladder Cancer
- Endometrial Cancer
- HER2-positive Breast Cancer
- Carcinoma, Small Cell
- Inflammatory Breast Cancer
- Biliary Tract Cancer
- Carcinoma, Ductal
- HER2-positive Gastric Cancer
- HER-2 Gene Amplification
- HER2-positive Solid Tumors
- HER-2 Protein Overexpression
- Carcinoma, Squamous
- Malignant Neoplasms
- Lung Cancer, Small Cell
- HER2-positive
- Lung Cancer, Non-Small-Cell
- Esophagogastric Junction Neoplasms
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
Enrollment (Estimated)
Phase
- Phase 1
Contacts and Locations
Study Contact
- Name: Ramona Swaby, MD, Vice President - Clinical Development
- Phone Number: (610) 427-3494
- Email: Ramona.Swaby@carismatx.com
Study Locations
-
-
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
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
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
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.
|
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. |
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).
|
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. |
anti-HER2 CAR macrophages
anti-PD antibody
Other Names:
|
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
Sponsor
Investigators
- Study Director: Jeanett Wetzel, Carisma Therapeutics
Publications and helpful links
Helpful Links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Digestive System Diseases
- Skin Diseases
- Respiratory Tract Diseases
- Neoplasms by Histologic Type
- Lung Diseases
- Urogenital Neoplasms
- Neoplasms by Site
- Adenocarcinoma
- Neoplasms, Glandular and Epithelial
- Uterine Neoplasms
- Genital Neoplasms, Female
- Uterine Diseases
- Endocrine System Diseases
- Ovarian Diseases
- Adnexal Diseases
- Gonadal Disorders
- Gastrointestinal Neoplasms
- Digestive System Neoplasms
- Gastrointestinal Diseases
- Stomach Diseases
- Endocrine Gland Neoplasms
- Genital Neoplasms, Male
- Breast Diseases
- Liver Diseases
- Prostatic Diseases
- Respiratory Tract Neoplasms
- Thoracic Neoplasms
- Carcinoma, Bronchogenic
- Bronchial Neoplasms
- Liver Neoplasms
- Biliary Tract Diseases
- Neoplasms, Squamous Cell
- Bile Duct Diseases
- Neoplasms, Ductal, Lobular, and Medullary
- Female Urogenital Diseases
- Female Urogenital Diseases and Pregnancy Complications
- Urogenital Diseases
- Male Urogenital Diseases
- Genital Diseases, Male
- Genital Diseases
- Genital Diseases, Female
- Neoplasms
- Stomach Neoplasms
- Breast Neoplasms
- Head and Neck Neoplasms
- Prostatic Neoplasms
- Lung Neoplasms
- Carcinoma, Non-Small-Cell Lung
- Carcinoma
- Carcinoma, Hepatocellular
- Ovarian Neoplasms
- Endometrial Neoplasms
- Small Cell Lung Carcinoma
- Carcinoma, Ovarian Epithelial
- Carcinoma, Squamous Cell
- Carcinoma, Transitional Cell
- Carcinoma, Small Cell
- Inflammatory Breast Neoplasms
- Biliary Tract Neoplasms
- Carcinoma, Ductal
- Bile Duct Neoplasms
- Molecular Mechanisms of Pharmacological Action
- Antineoplastic Agents
- Antineoplastic Agents, Immunological
- Immune Checkpoint Inhibitors
- Pembrolizumab
Other Study ID Numbers
- 101 (Hamilton Integrated Research Ethics Board)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
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.
Clinical Trials on Adenocarcinoma
-
Criterium, Inc.University of Colorado, Denver; NovartisTerminatedPancreatic Adenocarcinoma | Gastric Adenocarcinoma | Cholangiocarcinoma | Esophageal Adenocarcinoma | Colorectal Adenocarcinoma | Hepatocellular AdenocarcinomaUnited States
-
University of ChicagoCompletedGastric Adenocarcinoma | Esophageal Adenocarcinoma | Gastroesophageal Junction AdenocarcinomaUnited States
-
Weill Medical College of Cornell UniversityMerck Sharp & Dohme LLC; Oncolys BioPharma IncNot yet recruitingGastric Adenocarcinoma | Esophageal Adenocarcinoma | Gastroesophageal Junction AdenocarcinomaUnited States
-
Alliance for Clinical Trials in OncologyNational Cancer Institute (NCI)RecruitingClinical Stage III Gastric Cancer AJCC v8 | Clinical Stage III Gastroesophageal Junction Adenocarcinoma AJCC v8 | Clinical Stage IV Gastric Cancer AJCC v8 | Clinical Stage IV Gastroesophageal Junction Adenocarcinoma AJCC v8 | Metastatic Gastric Adenocarcinoma | Metastatic Gastroesophageal Junction... and other conditionsUnited States, Puerto Rico
-
Roswell Park Cancer InstituteUnited States Department of DefenseRecruitingClinical Stage III Gastroesophageal Junction Adenocarcinoma AJCC v8 | Clinical Stage IV Gastroesophageal Junction Adenocarcinoma AJCC v8 | Metastatic Gastroesophageal Junction Adenocarcinoma | Unresectable Gastroesophageal Junction Adenocarcinoma | Locally Advanced Gastroesophageal Junction... and other conditionsUnited States
-
Wake Forest University Health SciencesNational Cancer Institute (NCI)RecruitingPancreas Adenocarcinoma | Locally Advanced Pancreatic Adenocarcinoma | Borderline Resectable Pancreatic AdenocarcinomaUnited States
-
Gynecologic Oncology GroupNational Cancer Institute (NCI)CompletedRecurrent Uterine Corpus Carcinoma | Endometrial Clear Cell Adenocarcinoma | Endometrial Serous Adenocarcinoma | Endometrial Undifferentiated Carcinoma | Endometrial Adenocarcinoma | Endometrial Transitional Cell Carcinoma | Endometrial Mucinous Adenocarcinoma | Endometrial Mixed Adenocarcinoma | Endometrial...United States
-
M.D. Anderson Cancer CenterNational Cancer Institute (NCI)RecruitingGastroesophageal Junction Adenocarcinoma | Clinical Stage II Esophageal Adenocarcinoma AJCC v8 | Clinical Stage IIA Esophageal Adenocarcinoma AJCC v8 | Clinical Stage III Esophageal Adenocarcinoma AJCC v8 | Pathologic Stage II Esophageal Adenocarcinoma AJCC v8 | Pathologic Stage IIA Esophageal... and other conditionsUnited States
-
Gynecologic Oncology GroupNational Cancer Institute (NCI)CompletedRecurrent Uterine Corpus Carcinoma | Endometrial Clear Cell Adenocarcinoma | Endometrial Serous Adenocarcinoma | Endometrial Undifferentiated Carcinoma | Endometrial Adenocarcinoma | Endometrial Transitional Cell Carcinoma | Endometrial Mucinous Adenocarcinoma | Endometrial Mixed Adenocarcinoma | Endometrial...United States
-
Gynecologic Oncology GroupNational Cancer Institute (NCI)CompletedStage III Uterine Corpus Cancer | Stage IV Uterine Corpus Cancer | Endometrial Clear Cell Adenocarcinoma | Endometrial Serous Adenocarcinoma | Endometrial AdenocarcinomaUnited States
Clinical Trials on CT-0508
-
CelltrionCompleted
-
University of PittsburghTerminatedCarcinoma, Squamous Cell of Head and NeckUnited States
-
Northwell HealthHeartFlow, Inc.CompletedAngina, Stable Chest Pain
-
Peter MacCallum Cancer Centre, AustraliaMelbourne Health; Westmead Hospital; Victorian Infectious Diseases Reference...CompletedAcute Myeloid Leukemia | Febrile Neutropenia | Acute Lymphoblastic Leukemia | Haematopoietic Stem Cell Transplant, Autologous | Haematopoietic Stem Cell Transplant, AllogeneicAustralia
-
Northwell HealthToshiba America Medical Systems, Inc.Enrolling by invitationCoronary Artery Disease | Chest Pain | Acute Coronary Syndrome | Acute Myocardial InfarctionUnited States
-
Seoul National University Bundang HospitalGE Healthcare; National Research Foundation of KoreaCompletedAppendicitisKorea, Republic of
-
Ankara Yildirim Beyazıt UniversityCompletedPain | Shoulder SyndromeTurkey
-
The University of Texas Health Science Center at...Recruiting
-
UMC UtrechtDutch Heart FoundationUnknown