Clinical trial NCT04660929: 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
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
Conditions: 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
Lead sponsor: Carisma Therapeutics Inc
Sponsor class: INDUSTRY
First posted: 2020-12-09
Enrollment: 48
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

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

Primary outcomes:
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.
timeFrame: 14 months
measure: Assess the feasibility of manufacturing CT-0508 by describing the percentage of products passing release criteria.
timeFrame: 12 months
measure: 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)
timeFrame: 14 months
Secondary outcomes:
measure: 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.
timeFrame: 24 months
measure: Estimate progression-free survival (PFS).
timeFrame: 24 months
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope National Medical Center
state: California
city: Chapel Hill
country: United States
facility: UNC Lineberger Comprehensive Cancer Center
state: North Carolina
city: Portland
country: United States
facility: OHSU Knight Cancer Institute
state: Oregon
city: Philadelphia
country: United States
facility: Abramson Cancer Center
state: Pennsylvania
city: Nashville
country: United States
facility: Tennessee Oncology / Sarah Cannon Research Institute
state: Tennessee
city: Houston
country: United States
facility: M D Anderson Cancer Center
state: Texas
city: Seattle
country: United States
facility: Fred Hutchinson Cancer Center
state: Washington
Study officials:
affiliation: Carisma Therapeutics
name: Jeanett Wetzel
role: STUDY_DIRECTOR
References:
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.