HER2-positivePhase 1NCT04660929
CAR-macrophages for the Treatment of HER2 Overexpressing Solid Tumors
A Phase 1 study testing CT-0508 and Pembrolizumab in people with HER2-positive and Adenocarcinoma, run by Carisma Therapeutics Inc at 7 sites in United States.
Trial summary
Phase 1, first-in-human, open label study of CAR macrophages in HER2 overexpressing solid tumors. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- HER2-positive, Adenocarcinoma, Bile Duct Cancer
- What is being tested?
- CT-0508 and Pembrolizumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 48 participants
- Where
- 7 sitesUnited States
- Study dates
- 2 Feb 2021to 31 Dec 2024
- Phase
- Phase 1
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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.
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- CT-0508 in Combination with Pembrolizumab Substudy Only:
- 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
Trial locations and contacts
7 sites in 1 country.
7 sites in 1 country
United States7 sites
UNC Lineberger Comprehensive Cancer Center
Chapel Hill, North Carolina, 27599
City of Hope National Medical Center
Duarte, California, 91010
M D Anderson Cancer Center
Houston, Texas, 77030
Tennessee Oncology / Sarah Cannon Research Institute
Nashville, Tennessee, 37203
Abramson Cancer Center
Philadelphia, Pennsylvania, 19104
OHSU Knight Cancer Institute
Portland, Oregon, 97239
Fred Hutchinson Cancer Center
Seattle, Washington, 98109
About this study
Official title: 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 1, first-in-human, open label study of CAR macrophages in HER2 overexpressing solid tumors.
Read the 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
- Conditions
- HER2-positive, Adenocarcinoma, Bile Duct Cancer, Biliary Tract Cancer, Bladder Cancer, Breast Cancer
- Being tested
- CT-0508, Pembrolizumab
- 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
- Medical subject headings
- Adenocarcinoma, Bile Duct Neoplasms, Biliary Tract Neoplasms, Urinary Bladder Neoplasms, Breast Neoplasms, Carcinoma, Ductal, Carcinoma, Hepatocellular, Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CT-0508Biological
anti-HER2 CAR macrophages
PembrolizumabBiological
Also called Keytruda
anti-PD antibody
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Biological: CT-0508 |
| 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. Receives: Biological: CT-0508 |
| 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). Receives: Biological: CT-0508 |
| 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. Receives: Biological: CT-0508; Biological: Pembrolizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
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)
Measured: 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.
Measured: 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)
Measured: 14 months
Secondary outcomes (2)
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.
Measured: 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.
Measured: 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Dec 2020
- Study start2 Feb 2021
- Primary completion31 Dec 2024 (estimated)
- Study completion31 Dec 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for HER2-positiveStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 48 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Carisma Therapeutics Inc
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Jeanett Wetzel, Study director, Carisma Therapeutics
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04660929
- Sponsor's protocol ID
- 101
- Status last verified
- Apr 2024
- First submitted
- 23 Nov 2020
- Last updated
- 18 Dec 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
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.
PubMed 32361713Reiss 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.
PubMed 39920391Li D, Yang Y, Zheng G, Meng L, Shang L, Ren J, Wang L, Bao Y. The potential of cellular homing behavior in tumor immunotherapy: from basic discoveries to clinical applications of immune, mesenchymal stem, and cancer cell homing. Front Immunol. 2024 Dec 12;15:1495978. doi: 10.3389/fimmu.2024.1495978. eCollection 2024.
PubMed 39726590Sly 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.
PubMed 36441083