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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
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Group 1 and Group 2 | Experimental | 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. |
|
| Intraperitoneal Administration | Experimental | 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 CT-0508 | Experimental | 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). |
|
| CT-0508 in Combination with Pembrolizumab | Experimental | 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. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| CT-0508 | Biological | anti-HER2 CAR macrophages |
|
| 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 |
| 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. |
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Inclusion Criteria:
HER2-positive recurrent or metastatic solid tumors for which there are no available curative treatment options.
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:
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| Name | Affiliation | Role |
|---|---|---|
| Jeanett Wetzel | Carisma Therapeutics | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| City of Hope National Medical Center | Duarte | California | 91010 | United States | ||
| UNC Lineberger Comprehensive Cancer Center |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 32361713 | Background | 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. | |
| 39920391 |
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|
| Pembrolizumab | Biological | anti-PD antibody |
|
|
| 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 |
| Chapel Hill |
| North Carolina |
| 27599 |
| United States |
| OHSU Knight Cancer Institute | Portland | Oregon | 97239 | United States |
| Abramson Cancer Center | Philadelphia | Pennsylvania | 19104 | United States |
| Tennessee Oncology / Sarah Cannon Research Institute | Nashville | Tennessee | 37203 | United States |
| M D Anderson Cancer Center | Houston | Texas | 77030 | United States |
| Fred Hutchinson Cancer Center | Seattle | Washington | 98109 | United States |
| Derived |
| Reiss KA, Angelos MG, Dees EC, Yuan Y, Ueno NT, Pohlmann PR, Johnson ML, Chao J, Shestova O, Serody JS, Schmierer M, Kremp M, Ball M, Qureshi R, Schott BH, Sonawane P, DeLong SC, Christiano M, Swaby RF, Abramson S, Locke K, Barton D, Kennedy E, Gill S, Cushing D, Klichinsky M, Condamine T, Abdou Y. CAR-macrophage therapy for HER2-overexpressing advanced solid tumors: a phase 1 trial. Nat Med. 2025 Apr;31(4):1171-1182. doi: 10.1038/s41591-025-03495-z. Epub 2025 Feb 7. |
| 36441083 | Derived | Sly LM, McKay DM. Macrophage immunotherapy: overcoming impediments to realize promise. Trends Immunol. 2022 Dec;43(12):959-968. doi: 10.1016/j.it.2022.10.002. Epub 2022 Oct 29. |
| ID | Term |
|---|---|
| D000230 | Adenocarcinoma |
| D001650 | Bile Duct Neoplasms |
| D001661 | Biliary Tract Neoplasms |
| D001749 | Urinary Bladder Neoplasms |
| D001943 | Breast Neoplasms |
| D044584 | Carcinoma, Ductal |
| D006528 | Carcinoma, Hepatocellular |
| D009369 | Neoplasms |
| D002289 | Carcinoma, Non-Small-Cell Lung |
| D000077216 | Carcinoma, Ovarian Epithelial |
| D018288 | Carcinoma, Small Cell |
| D002294 | Carcinoma, Squamous Cell |
| D002295 | Carcinoma, Transitional Cell |
| D015179 | Colorectal Neoplasms |
| D058922 | Inflammatory Breast Neoplasms |
| D013274 | Stomach Neoplasms |
| D010051 | Ovarian Neoplasms |
| D010190 | Pancreatic Neoplasms |
| D011471 | Prostatic Neoplasms |
| D006258 | Head and Neck Neoplasms |
| D016889 | Endometrial Neoplasms |
| D055752 | Small Cell Lung Carcinoma |
| D009362 | Neoplasm Metastasis |
| ID | Term |
|---|---|
| D002277 | Carcinoma |
| D009375 | Neoplasms, Glandular and Epithelial |
| D009370 | Neoplasms by Histologic Type |
| D004067 | Digestive System Neoplasms |
| D009371 | Neoplasms by Site |
| D001649 | Bile Duct Diseases |
| D001660 | Biliary Tract Diseases |
| D004066 | Digestive System Diseases |
| D014571 | Urologic Neoplasms |
| D014565 | Urogenital Neoplasms |
| D052776 | Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D001745 | Urinary Bladder Diseases |
| D014570 | Urologic Diseases |
| D052801 | Male Urogenital Diseases |
| D001941 | Breast Diseases |
| D012871 | Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |
| D018299 | Neoplasms, Ductal, Lobular, and Medullary |
| D008113 | Liver Neoplasms |
| D008107 | Liver Diseases |
| D002283 | Carcinoma, Bronchogenic |
| D001984 | Bronchial Neoplasms |
| D008175 | Lung Neoplasms |
| D012142 | Respiratory Tract Neoplasms |
| D013899 | Thoracic Neoplasms |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D004701 | Endocrine Gland Neoplasms |
| D010049 | Ovarian Diseases |
| D000291 | Adnexal Diseases |
| D005831 | Genital Diseases, Female |
| D005833 | Genital Neoplasms, Female |
| D000091662 | Genital Diseases |
| D004700 | Endocrine System Diseases |
| D006058 | Gonadal Disorders |
| D018307 | Neoplasms, Squamous Cell |
| D007414 | Intestinal Neoplasms |
| D005770 | Gastrointestinal Neoplasms |
| D005767 | Gastrointestinal Diseases |
| D003108 | Colonic Diseases |
| D007410 | Intestinal Diseases |
| D012002 | Rectal Diseases |
| D013272 | Stomach Diseases |
| D010182 | Pancreatic Diseases |
| D005834 | Genital Neoplasms, Male |
| D005832 | Genital Diseases, Male |
| D011469 | Prostatic Diseases |
| D014594 | Uterine Neoplasms |
| D014591 | Uterine Diseases |
| D009385 | Neoplastic Processes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
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| ID | Term |
|---|---|
| C582435 | pembrolizumab |
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