AzTrials
AzTrials

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.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
Search all trials

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
Are there results?
None posted in the registry

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.
Show all 11Show fewer
  • 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

Other trials in United States

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

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 groups in NCT04660929
Study groupRoleWhat they receive
Group 1 and Group 2ExperimentalBoth 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 AdministrationExperimentalAll 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-0508Experimental89[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 PembrolizumabExperimentalAll 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.

  1. 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

  2. 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

  3. 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)

  1. 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

  2. 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.

  1. First posted9 Dec 2020
  2. Study start2 Feb 2021
  3. Primary completion31 Dec 2024 (estimated)
  4. Study completion31 Dec 2024 (estimated)

Resources

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)
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 32361713

  • 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.

    PubMed 39920391

  • Li 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 39726590

  • 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.

    PubMed 36441083

Questions about this trial

What is this clinical trial studying?

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.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 18 Dec 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 7 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Assess the safety and tolerability of CT-0508 by estimating the frequency and severity of adverse events in subjects with HER2 overexpressing solid tumors. (time frame: 14 months). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04660929, which also lists 4 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Dec 2024.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in