Back to resultsCAR-macrophages for the Treatment of HER2 Overexpressing Solid Tumors
Primary Purpose
HER2-positive, Adenocarcinoma, Bile Duct Cancer
Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
CT-0508
Pembrolizumab
Sponsored by
About this trial
This is an interventional treatment trial for HER2-positive focused on measuring 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
Eligibility Criteria
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
Sites / Locations
- City of Hope National Medical CenterRecruiting
- UNC Lineberger Comprehensive Cancer CenterRecruiting
- OHSU Knight Cancer InstituteRecruiting
- Abramson Cancer CenterRecruiting
- Tennessee Oncology / Sarah Cannon Research InstituteRecruiting
- M D Anderson Cancer CenterRecruiting
- Fred Hutchinson Cancer CenterRecruiting
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Experimental
Experimental
Experimental
Experimental
Arm Label
Group 1 and Group 2
Intraperitoneal Administration
89[Zr]radiolabeled CT-0508
CT-0508 in Combination with Pembrolizumab
Arm Description
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.
Outcomes
Primary Outcome Measures
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)
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.
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)
Secondary Outcome Measures
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.
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.
Full Information
NCT ID
NCT04660929
First Posted
November 23, 2020
Last Updated
December 15, 2022
Sponsor
Carisma Therapeutics Inc
1. Study Identification
Unique Protocol Identification Number
NCT04660929
Brief Title
CAR-macrophages for the Treatment of HER2 Overexpressing Solid Tumors
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
Study Type
Interventional
2. Study Status
Record Verification Date
December 2022
Overall Recruitment Status
Recruiting
Study Start Date
February 2, 2021 (Actual)
Primary Completion Date
July 2023 (Anticipated)
Study Completion Date
December 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Carisma Therapeutics Inc
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
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
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
HER2-positive, Adenocarcinoma, Bile Duct Cancer, Biliary Tract Cancer, Bladder Cancer, Breast Cancer, Breast Neoplasm, Carcinoma, Ductal, Carcinoma, Hepatocellular, Cancer, Lung Cancer, Non-Small-Cell, Carcinoma, Ovarian Epithelial, Carcinoma, Small Cell, Carcinoma, Squamous, Carcinoma, Transitional Cell, Colorectal Cancer, Esophagogastric Junction Neoplasms, Inflammatory Breast Cancer, Stomach Neoplasms, Malignant Neoplasms, 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
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
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
48 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Group 1 and Group 2
Arm Type
Experimental
Arm Description
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.
Arm Title
Intraperitoneal Administration
Arm Type
Experimental
Arm Description
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.
Arm Title
89[Zr]radiolabeled CT-0508
Arm Type
Experimental
Arm Description
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).
Arm Title
CT-0508 in Combination with Pembrolizumab
Arm Type
Experimental
Arm Description
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.
Intervention Type
Biological
Intervention Name(s)
CT-0508
Intervention Description
anti-HER2 CAR macrophages
Intervention Type
Biological
Intervention Name(s)
Pembrolizumab
Other Intervention Name(s)
Keytruda
Intervention Description
anti-PD antibody
Primary Outcome Measure Information:
Title
Assess the safety and tolerability of CT-0508 by estimating the frequency and severity of adverse events in subjects with HER2 overexpressing solid tumors.
Description
Frequency and severity of adverse events including, but not limited to, estimating frequency and severity of Cytokine Release Syndrome (CRS)
Time Frame
14 months
Title
Assess the feasibility of manufacturing CT-0508 by describing the percentage of products passing release criteria.
Description
Percentage of products that pass release criteria among all manufactured products.
Time Frame
12 months
Title
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)
Description
Frequency and severity of adverse events including, but not limited to, estimating frequency and severity of Cytokine Release Syndrome (CRS)
Time Frame
14 months
Secondary Outcome Measure Information:
Title
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.
Description
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.
Time Frame
24 months
Title
Estimate progression-free survival (PFS).
Description
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.
Time Frame
24 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Ramona Swaby, MD, Vice President - Clinical Development
Phone
(610) 427-3494
Email
Ramona.Swaby@carismatx.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ramona Swaby, MD
Organizational Affiliation
Carisma Therapeutics
Official's Role
Study Director
Facility Information:
Facility Name
City of Hope National Medical Center
City
Duarte
State/Province
California
ZIP/Postal Code
91010
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Joanne E Mortimer, MD
Phone
626-218-9200
Email
jmortimer@coh.org
Facility Name
UNC Lineberger Comprehensive Cancer Center
City
Chapel Hill
State/Province
North Carolina
ZIP/Postal Code
27599
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Cheng
Phone
919-445-4208
Email
catherine_cheng@med.unc.edu
Facility Name
OHSU Knight Cancer Institute
City
Portland
State/Province
Oregon
ZIP/Postal Code
97239
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Richard Maziarz, MD
Phone
503-494-1080
Email
trials@ohsu.edu
Facility Name
Abramson Cancer Center
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Ciminera
Phone
215-220-9678
Email
krista.ciminera@pennmedicine.upenn.edu
Facility Name
Tennessee Oncology / Sarah Cannon Research Institute
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37203
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
AskSarah
Phone
615-329-7274
First Name & Middle Initial & Last Name & Degree
Melissa Johnson, MD
Facility Name
M D Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Angela Alexander
Phone
713-792-9137
Email
Aalexand@mdanderson.org
Facility Name
Fred Hutchinson Cancer Center
City
Seattle
State/Province
Washington
ZIP/Postal Code
98109
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
SCCA Intake
Phone
206-606-1024
Email
hutchdoc@seattlecca.org
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
32361713
Citation
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.
Results Reference
background
Links:
URL
http://www.her2macrophagetrial.com/
Description
Carisma Therapeutics Clinical Trial website
Learn more about this trial
CAR-macrophages for the Treatment of HER2 Overexpressing Solid Tumors
We'll reach out to this number within 24 hrs