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

NCT04025216 | Terminated Phase 1 DMC FDA Drug

• 1 other identifier: CART-TnMUC1-01
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 10

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).

Conditions

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

Keywords

Chimeric Antigen Receptor (CAR); T-cells; TnMUC1

Outcome Measures

Primary Outcomes (2)

• Dose Escalation: Dose Identification of CART-TnMUC1

  Incidence of Dose Limiting Toxicity (DLT) in solid tumors and multiple myeloma

  Up to 2 years

• Cohort Expansion: Objective Response in solid tumors

  Proportion of patients having a confirmed Complete Response (CR) or Partial Response (PR) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1

  Up to 2 years

Secondary Outcomes (12)

• Safety of CART-TnMUC1 in solid tumors and multiple myeloma

  Up to 2 years

• Tolerability of CART-TnMUC1 in solid tumors and multiple myeloma

  Up to 2 years

• Feasibility of CART-TnMUC1 in solid tumors and multiple myeloma

  Up to 2 years

• Preliminary anti-tumor efficacy of CART as assessed by Overall Survival (OS) in solid tumors and multiple myeloma

  Up to 2 years

• Preliminary anti-tumor efficacy of CART as assessed by Progression Free Survival (PFS) in solid tumors

  Up to 2 years

Study Arms (2)

Dose Escalation Arm1: Solid Tumors

EXPERIMENTAL

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

Biological: CART-TnMUC1; Drug: Cyclophosphamide; Drug: Fludarabine

Dose Escalation Arm 2: Multiple Myeloma

EXPERIMENTAL

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

Biological: CART-TnMUC1; Drug: Cyclophosphamide; Drug: Fludarabine

Interventions

CART-TnMUC1 BIOLOGICAL

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

Dose Escalation Arm 2: Multiple Myeloma; Dose Escalation Arm1: Solid Tumors

Cyclophosphamide DRUG

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

Dose Escalation Arm 2: Multiple Myeloma; Dose Escalation Arm1: Solid Tumors

Fludarabine DRUG

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

Dose Escalation Arm 2: Multiple Myeloma; Dose Escalation Arm1: Solid Tumors

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Kite, A Gilead Company: lead

Study Sites (10)

Mayo Clinic of Arizona

Phoenix, Arizona, 85054, United States

Location

The Angeles Clinic and Research Institute

Los Angeles, California, 90025, United States

Location

Moffitt Cancer Center

Tampa, Florida, 33637, United States

Location

University of Chicago Medical Center

Chicago, Illinois, 60637, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Hospital of the University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, 15232, United States

Location

Sarah Cannon Research Institute

Nashville, Tennessee, 37203, United States

Location

The University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

University of Washington Medical Center

Seattle, Washington, 98195, United States

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Ovarian Neoplasms; Fallopian Tube Neoplasms; Triple Negative Breast Neoplasms; Multiple Myeloma

Interventions

Cyclophosphamide; fludarabine

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Endocrine Gland Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders; Fallopian Tube Diseases; Breast Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Parallel arms with sequential dose escalation

Study Record Dates

• First Submitted: July 12, 2019
• First Posted: July 18, 2019
• Study Start: October 10, 2019
• Primary Completion: December 2, 2022
• Study Completion: December 2, 2022
• Last Updated: January 24, 2024

Record last verified: 2023-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (10)