Brief Title
A Study of CART-TnMUC1 in Patients With TnMUC1-Positive Advanced Cancers
Official Title
A Phase 1 Open-Label, Multi-Center First in Human Study of TnMUC1-Targeted Genetically-Modified Chimeric Antigen Receptor T Cells in Patients With Advanced TnMUC1-Positive Solid Tumors and Multiple Myeloma
Brief Summary
Multi-center, open-label, first in human Phase 1 study of the safety, tolerability,
feasibility, and preliminary efficacy of the administration of genetically modified
autologous T cells (CART-TnMUC1 cells) engineered to express a chimeric antigen receptor
(CAR) capable of recognizing the tumor antigen, TnMUC1 and activating the T cell (CART-
TnMUC1 cells).
Detailed Description
The Dose Escalation phase of the study is designed to identify the dose and regimen of
CART-TnMUC1 cells that can be safely administered intravenously following the lymphodepletion
(LD) regimen to patients with (1) advanced TnMUC1+ solid tumors (triple negative breast
cancer, epithelial ovarian cancer, pancreatic cancer, and non-small cell lung cancer) and (2)
advanced TnMUC1+ multiple myeloma in a parallel two-arm dose escalation study. The Dose
Escalation phase is anticipated to enroll approximately 40 patients.
The Expansion phase of the study is designed to assess the preliminary efficacy of
CART-TnMUC1 cells administered intravenously to patients with TnMUC1+ solid tumors. The
Expansion phase is anticipated to enroll approximately 72 patients (18 patients per each
tumor indication).
Study Phase
Phase 1
Study Type
Interventional
Primary Outcome
Dose Escalation: Dose Identification of CART-TnMUC1
Secondary Outcome
Safety of CART-TnMUC1 in solid tumors and multiple myeloma
Condition
Non-Small Cell Lung Cancer
Intervention
CART-TnMUC1
Study Arms / Comparison Groups
Dose Escalation Arm1: Solid Tumors
Description: Intravenous CART-TnMUC1 cells for patients with TnMUC1+ treatment-resistant ovarian cancer (including cancers of the fallopian tube), pancreatic ductal adenocarcinoma, hormone receptor (HR)-negative and human epidermal growth factor receptor 2 (HER2)-negative (triple negative) breast cancer and non-small cell lung cancer
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Biological
Estimated Enrollment
112
Start Date
October 10, 2019
Completion Date
October 31, 2036
Primary Completion Date
December 31, 2022
Eligibility Criteria
Key Inclusion Criteria:
- Confirmed diagnosis of metastatic treatment-resistant ovarian cancer (including
cancers of the fallopian tube), pancreatic adenocarcinoma, hormone receptor
(HR)-negative and HER2-negative (triple negative) breast cancer (TNBC) or non-small
cell lung cancer (NSCLC), or relapsed/refractory multiple myeloma
- Eastern Cooperative Oncology Group (ECOG) score of 0 or 1
- Prior therapies as defined by tumor type:
- Multiple myeloma: relapsed or refractory disease previously treated with or
intolerant to at least three different lines of therapy that contained at least
one of the following drug classes: proteasome inhibitor, an immune modulatory
drug, alkylators, CD38 monoclonal antibody and glucocorticoids. Patients must be
at least 90 days since autologous stem cell transplant
- NSCLC: i.) Patients without driver mutations must have received standard therapy,
including both checkpoint inhibition and platinum-based chemotherapy or be
intolerant of these standard therapies ii.) Patients with driver mutations must
have received or be intolerant to prior targeted therapy directed at the specific
identified mutations in addition to the standard chemotherapy classes
- Pancreatic adenocarcinoma: disease progression following at least one standard of
care systemic chemotherapy for metastatic or unresectable disease or be
intolerant of these standard therapies
- TNBC: ER and/or PR < or =10%, HER2 negative and experienced disease progression
following at least one prior systemic anti-cancer therapy regimen as part of
their treatment for management of metastatic breast cancer or be intolerant to
these standard therapies
- Ovarian: platinum-resistant (progression of disease by either CA-125, clinical or
radiographic assessment within 6 months of last platinum-based chemotherapy ) and
must have received at least two prior lines of therapy for metastatic ovarian
cancer, including at least one prior line of therapy including a
platinum-containing regimen or be intolerant of these standard therapies
- Evaluable disease as defined by tumor type
- TnMUC1+ disease, determined by centrally tested TnMUC1 expression in a prior or
archival tumor biopsy
- Toxicities from any previous therapy must have recovered to Grade 1 or baseline
- Estimated estimated glomerular filtration rate ≥ 60 m/min by Modification of Diet in
Renal Disease criteria
- Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ≤ 2.5 x upper
institutional limit of normal with the following exception: Patients with known
hepatic metastases, AST or ALT ≤ 3 x upper institutional limit of normal
- Serum total bilirubin < 1.5 mg/dL with the following exception: patients with known
Gilbert's disease, serum total bilirubin < 3 mg/dL
- Serum albumin ≥ 3.0 g/dL (solid tumor patients in Arm 1 and Phase 1a only, not
applicable to patients with multiple myeloma)
- Left ventricular ejection fraction (LVEF) ≥ 50%. LVEF assessment must have been
performed within 6 months of treatment start
- Hemoglobin ≥ 8 g/dL
- Absolute neutrophil count ≥ 1000/μL
- Platelet count ≥ 75,000/μL (for Multiple Myeloma patients with bone marrow plasma
cells ≥ 50% of cellularity: ≥ 30,000/μL)
- Patients of reproductive potential agree to use approved contraceptive methods per
protocol
Key Exclusion Criteria:
- Active invasive cancer other than the proposed cancers included in the study
- Current treatment with systemic high-dose corticosteroids (defined as a dose greater
than the equivalent of prednisone 10 mg/day)
- Active autoimmune disease (including connective tissue disease, uveitis, sarcoidosis,
inflammatory bowel disease or multiple sclerosis) or have a history of severe
autoimmune disease requiring prolonged immunosuppressive therapy (any
immunosuppressive therapy should have been stopped within 6 weeks prior to screening
visit)
- Current human immunodeficiency virus (HIV), hepatitis C virus (HCV), hepatitis B virus
(HBV) infections
- Other active or uncontrolled medical or psychiatric condition that would preclude
participation in the opinion of the Sponsor or Principal Investigator
- Prior allogeneic stem cell transplant
- Active and untreated central nervous system (CNS) malignancy
- History of severe infusion reaction to monoclonal antibodies or biological therapies,
or to study product excipients that would preclude the patient safely receiving
CART-TnMUC1 cells
- Active or recent (within the past 6 months prior to apheresis) cardiovascular disease,
defined as (1) New York Heart Association (NYHA) Class III or IV heart failure, (2)
unstable angina or (3) a history of recent (within 6 months) myocardial infarction or
sustained (> 30 second) ventricular tachyarrhythmias, or (4) cerebrovascular accident
- Have inadequate venous access for or contraindications for the apheresis procedure
- Pregnant or breastfeeding women
Gender
All
Ages
18 Years - N/A
Accepts Healthy Volunteers
No
Contacts
, 215-966-1472, [email protected]
Location Countries
United States
Location Countries
United States
Administrative Informations
NCT ID
NCT04025216
Organization ID
CART-TnMUC1-01
Responsible Party
Sponsor
Study Sponsor
Tmunity Therapeutics
Study Sponsor
, ,
Verification Date
April 2021