A Study of CART-TnMUC1 in Patients With TnMUC1-Positive Advanced Cancers

Study Purpose

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).

Recruitment Criteria

Accepts Healthy Volunteers

Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms

No
Study Type

An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes.


An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes.


Searching Both is inclusive of interventional and observational studies.

Interventional
Eligible Ages 18 Years and Over
Gender All
More Inclusion & Exclusion 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

Trial Details

Trial ID:

This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.

NCT04025216
Phase

Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans.

Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data.

Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs.

Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.

Phase 1
Lead Sponsor

The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.

Tmunity Therapeutics
Principal Investigator

The person who is responsible for the scientific and technical direction of the entire clinical study.

N/A
Principal Investigator Affiliation N/A
Agency Class

Category of organization(s) involved as sponsor (and collaborator) supporting the trial.

Industry
Overall Status Recruiting
Countries United States
Conditions

The disease, disorder, syndrome, illness, or injury that is being studied.

Non-Small Cell Lung Cancer, Ovarian Cancer, Fallopian Tube Cancer, Triple Negative Breast Cancer, Multiple Myeloma, Pancreatic Ductal Adenocarcinoma
Additional Details

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).

Arms & Interventions

Arms

Experimental: Dose Escalation Arm1: Solid Tumors

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

Experimental: Dose Escalation Arm 2: Multiple Myeloma

Intravenous CART-TnMUC1 cells for patients with TnMUC1+ relapsed/refractory multiple myeloma

Interventions

Biological: - CART-TnMUC1

Single intravenous administration of genetically modified autologous T cells engineered to express a TnMUC1-Targeted Genetically-Modified Chimeric Antigen (CAR)

Drug: - Cyclophosphamide

Patients will receive cyclophosphamide and fludarabine lymphodepletion chemotherapy followed by the investigational product, CART-TnMUC1

Drug: - Fludarabine

Patients will receive cyclophosphamide and fludarabine lymphodepletion chemotherapy followed by the investigational product, CART-TnMUC1

Contact a Trial Team

If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.

Los Angeles, California

Status

Recruiting

Address

The Angeles Clinic and Research Institute

Los Angeles, California, 90025

Site Contact

Saba Mukarram

smukarram@theangelesclinic.org

310-231-2181

Moffitt Cancer Center, Tampa, Florida

Status

Recruiting

Address

Moffitt Cancer Center

Tampa, Florida, 33637

Site Contact

Dragana Lakic

dragana.lakic@moffitt.org

813-745-6699

University of Chicago Medical Center, Chicago, Illinois

Status

Recruiting

Address

University of Chicago Medical Center

Chicago, Illinois, 60637

Site Contact

Elaine Hoekstra

Ehoekstra1@medicine.bsd.uchicago.edu

773-834-8528

Washington University School of Medicine, Saint Louis, Missouri

Status

Recruiting

Address

Washington University School of Medicine

Saint Louis, Missouri, 63110

Site Contact

Nic Perry

nperry@wustl.edu

314-273-2831

Philadelphia, Pennsylvania

Status

Recruiting

Address

Hospital of the University of Pennsylvania

Philadelphia, Pennsylvania, 19104

Site Contact

Alfred Garfall, MD

PennCancerTrials@emergingmed.com

855-216-0098

University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania

Status

Recruiting

Address

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, 15232

Site Contact

Sarah Brodeur, BS

brodeurs@upmc.edu

412-623-2944

Sarah Cannon Research Institute, Nashville, Tennessee

Status

Recruiting

Address

Sarah Cannon Research Institute

Nashville, Tennessee, 37203

Site Contact

Melissa Johnson, MD

DDUreferrals@sarahcannon.com

615-329-7478

Houston, Texas

Status

Recruiting

Address

The University of Texas MD Anderson Cancer Center

Houston, Texas, 77030

Site Contact

So Jung Hong

shong7@mdanderson.org

713-563-0293

University of Washington Medical Center, Seattle, Washington

Status

Recruiting

Address

University of Washington Medical Center

Seattle, Washington, 98195

Site Contact

IMTX Intake Coordinator

immunotherapy@seattlecca.org

855-557-0555