CAR-macrophages For The Treatment Of HER2 Overexpressing Solid Tumors

Study Overview

CAR-macrophages for the Treatment of HER2 Overexpressing Solid Tumors

Phase 1, first-in-human, open label study of CAR macrophages in 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 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

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

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 Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 2020-11-23	Results First Submitted N/A	Last Update Submitted that met QC Criteria 2024-12-16
First Submitted that Met QC Criteria 2020-12-03	Results First Submitted that Met QC Criteria N/A	Last Update Posted (ACTUAL) 2024-12-18
First Posted (ACTUAL) 2020-12-09	Results First Posted N/A	Last Verified 2024-04

Study Plan

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

Design Details

Primary Purpose:
Treatment

Allocation:
Non Randomized

Interventional Model:
Parallel

Masking:
None

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	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 b	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	BIOLOGICAL: CT-0508 anti-HER2 CAR macrophages BIOLOGICAL: Pembrolizumab anti-PD antibody

Primary Outcome Measures	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.	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.	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)	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	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.	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).	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

Contacts and Locations

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

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.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
18 Years

Accepts Healthy Volunteers:

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

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.

Left ventricular ejection fraction (LVEF) <50% as determined by ECHO or multiple gated acquisition scan (MUGA)

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

Collaborators and Investigators

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

Investigators

STUDY_DIRECTOR: Jeanett Wetzel, Carisma Therapeutics

Publications

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

General Publications

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.

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