Adenocarcinoma, Bile Duct Cancer, Biliary Tract Cancer, Bladder Cancer, Breast Cancer, Breast Neoplasm, Cancer, Carcinoma, Ductal, Carcinoma, Hepatocellular, Carcinoma, Ovarian Epithelial, Carcinoma, Small Cell, Carcinoma, Squamous, Carcinoma, Transitional Cell, Colorectal Cancer, Endometrial Cancer, Esophagogastric Junction Neoplasms, Head and Neck Cancer, HER-2 Gene Amplification, HER2-positive, HER2-positive Breast Cancer, HER2-positive Gastric Cancer, HER2-positive Solid Tumors, HER-2 Protein Overexpression, Inflammatory Breast Cancer, Lung Cancer, Non-Small-Cell, Lung Cancer, Small Cell, Malignant Neoplasms, Ovarian Neoplasms, Pancreatic Cancer, Prostate Cancer, Stomach Neoplasms
Conditions
Keywords
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
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
Interventions
BIOLOGICALCT-0508
anti-HER2 CAR macrophages
BIOLOGICALPembrolizumab
anti-PD antibody
Sponsors
Carisma Therapeutics Inc
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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:
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
United States
Outcome results
None listed