CAR-macrophages for the Treatment of HER2 Overexpressing Solid Tumors

Phase 1

Active, not recruiting

• Conditions: HER2-positive; Carcinoma, Hepatocellular; Lung Cancer, Non-Small-Cell; Esophagogastric Junction Neoplasms; Inflammatory Breast Cancer; Prostate Cancer; Lung Cancer, Small Cell; Bile Duct Cancer; Carcinoma, Ductal; Cancer
• Interventions: Biological: CT-0508; Biological: Pembrolizumab

• Registration Number: NCT04660929
• Lead Sponsor: Carisma Therapeutics Inc

Brief Summary

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

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 Timeline

• Study First Submitted: 2020-11-23
• Study First Submitted QC: 2020-12-03
• Study First Posted: 2020-12-09
• Study Start: 2021-02-02
• Status Verified: 2024-04
• Last Update Submitted: 2024-12-16
• Last Update Posted: 2024-12-18
• Primary Completion: 2024-12-31
• Study Completion: 2024-12-31

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 48

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
89[Zr]radiolabeled CT-0508	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).
Intraperitoneal Administration	CT-0508	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.
CT-0508 in Combination with Pembrolizumab	CT-0508	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.
CT-0508 in Combination with Pembrolizumab	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.
Group 1 and Group 2	CT-0508	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.

Primary Outcome Measures

Name	Time	Method
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)	14 months	Frequency and severity of adverse events including, but not limited to, estimating frequency and severity of Cytokine Release Syndrome (CRS)
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

Name	Time	Method
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.

Trial Locations

Locations (7)

M D Anderson Cancer Center; 🇺🇸 Houston, Texas, United States

Abramson Cancer Center; 🇺🇸 Philadelphia, Pennsylvania, United States

Fred Hutchinson Cancer Center; 🇺🇸 Seattle, Washington, United States

Tennessee Oncology / Sarah Cannon Research Institute; 🇺🇸 Nashville, Tennessee, United States

City of Hope National Medical Center; 🇺🇸 Duarte, California, United States

UNC Lineberger Comprehensive Cancer Center; 🇺🇸 Chapel Hill, North Carolina, United States

OHSU Knight Cancer Institute; 🇺🇸 Portland, Oregon, United States