Title
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
Phase
Phase 1Lead Sponsor
Carisma TherapeuticsStudy Type
InterventionalStatus
RecruitingIndication/Condition
HER2-positive Adenocarcinoma Bile Duct Cancer Biliary Tract Cancer Bladder Cancer Carcinoma, Ductal Carcinoma, Hepatocellular Lung Cancer, Non-Small-Cell Carcinoma, Ovarian Epithelial Carcinoma, Small Cell Carcinoma, Squamous Carcinoma, Transitional Cell Colorectal Cancer Esophagogastric Junction Neoplasms Inflammatory Breast Cancer 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 ...Intervention/Treatment
CT-0508 ...Study Participants
48Phase 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
anti-HER2 CAR macrophages
anti-PD antibody
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.
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.
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).
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.
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
