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Non-Small Cell Lung CancerPhase 1NCT04025216

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

A Phase 1 study testing CART-TnMUC1, Cyclophosphamide and Fludarabine in people with Non-Small Cell Lung Cancer and Ovarian Cancer, run by Kite, A Gilead Company at 10 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
CART-TnMUC1, Cyclophosphamide and Fludarabine
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
16 participants
Where
10 sitesUnited States
Study dates
10 Oct 2019to 2 Dec 2022
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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

Who cannot join

  • 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
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  • 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 locations and contacts

10 sites in 1 country.

10 sites in 1 country

United States10 sites

  • University of Chicago Medical Center

    Chicago, Illinois, 60637

  • The University of Texas MD Anderson Cancer Center

    Houston, Texas, 77030

  • The Angeles Clinic and Research Institute

    Los Angeles, California, 90025

  • Sarah Cannon Research Institute

    Nashville, Tennessee, 37203

  • Hospital of the University of Pennsylvania

    Philadelphia, Pennsylvania, 19104

  • Mayo Clinic of Arizona

    Phoenix, Arizona, 85054

  • University of Pittsburgh Medical Center

    Pittsburgh, Pennsylvania, 15232

  • University of Washington Medical Center

    Seattle, Washington, 98195

  • Washington University School of Medicine

    St Louis, Missouri, 63110

  • Moffitt Cancer Center

    Tampa, Florida, 33637

Other trials in United States

About this study

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

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).

Read the 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).

Being tested
CART-TnMUC1, Cyclophosphamide, Fludarabine
Keywords
Chimeric Antigen Receptor (CAR), T-cells, TnMUC1
Medical subject headings
Carcinoma, Non-Small-Cell Lung, Ovarian Neoplasms, Fallopian Tube Neoplasms, Triple Negative Breast Neoplasms, Multiple Myeloma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CART-TnMUC1Biological

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

  • CyclophosphamideDrug

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

  • FludarabineDrug

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

Study groups in NCT04025216
Study groupRoleWhat they receive
Dose Escalation Arm1: Solid TumorsExperimentalIntravenous 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
Receives: Biological: CART-TnMUC1; Drug: Cyclophosphamide; Drug: Fludarabine
Dose Escalation Arm 2: Multiple MyelomaExperimentalIntravenous CART-TnMUC1 cells for patients with TnMUC1+ relapsed/refractory multiple myeloma
Receives: Biological: CART-TnMUC1; Drug: Cyclophosphamide; Drug: Fludarabine

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Dose Escalation: Dose Identification of CART-TnMUC1

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

    Measured: Up to 2 years

  2. 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

    Measured: Up to 2 years

Secondary outcomes (12)

  1. Safety of CART-TnMUC1 in solid tumors and multiple myeloma

    Percentage of patients experiencing adverse events (AEs), including serious and severe AEs overall, by dose level, and by severity Grade

    Measured: Up to 2 years

  2. Tolerability of CART-TnMUC1 in solid tumors and multiple myeloma

    Frequency of treatment emergent AEs, frequency of clinical changes from baseline in vital signs, changes in electrocardiogram, and hematology and chemistry laboratory shifts from baseline

    Measured: Up to 2 years

  3. Feasibility of CART-TnMUC1 in solid tumors and multiple myeloma

    Proportion of enrolled patients who did not receive CART-TnMUC1 cells

    Measured: Up to 2 years

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

    OS as defined by the interval between CART-TnMUC1 cell infusion and date of death by any cause

    Measured: Up to 2 years

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

    PFS as defined by the interval between CART-TnMUC1 cell infusion and date of disease progression by RECIST v1.1 or death in solid tumors and by International Myeloma Working Group (IMWG) criteria in multiple myeloma

    Measured: Up to 2 years

  6. Preliminary anti-tumor efficacy of CART as assessed by Objective Response Rate (ORR) in solid tumors and multiple myeloma

    Proportion of patients having a confirmed CR or PR per RECIST v1.1 in solid tumors and IMWG criteria (PR, Very Good PR, CR, Stringent CR) in multiple myeloma

    Measured: Up to 2 years

  7. Preliminary anti-tumor efficacy of CART as assessed by Clinical Benefit Rate in solid tumors

    Proportion of patients having a confirmed CR, PR, or Stable Disease (SD) per RECIST v1.1

    Measured: Up to 2 years

  8. Preliminary anti-tumor efficacy of CART as assessed by Duration of Response (DOR) in solid tumors and multiple myeloma

    DOR as defined by the interval of first documented response until first documented disease progression or death in solid tumors and multiple myeloma

    Measured: Up to 2 years

  9. Preliminary anti-tumor efficacy of CART as assessed by Time to Response (TTR) in solid tumors and multiple myeloma

    Time to Response as defined by the interval between CART-TnMUC1 cell infusion and first documented CR or PR per RECIST v1.1 in solid tumors and IMWG criteria in multiple myeloma

    Measured: Up to 2 years

  10. Preliminary anti-tumor efficacy of CART as assessed by Time to Progression (TTP) in multiple myeloma

    Time to Progression as defined by the interval between CART-TnMUC1 cell infusion and first documented progression or death due to disease per RECIST v1.1 in solid tumors and IMWG criteria in multiple myeloma

    Measured: Up to 2 years

  11. Preliminary anti-tumor efficacy of CART as assessed by Minimal Residual Disease (MRD) in multiple myeloma

    Defined by MRD-negative rate per IMWG criteria

    Measured: Up to 2 years

  12. Peripheral expansion and persistence of CART-TnMUC1 cells in solid tumors and multiple myeloma

    Defined as quantitative polymerase chain reaction (qPCR) documenting loss of CART cells

    Measured: Up to 15 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted18 Jul 2019
  2. Study start10 Oct 2019
  3. Primary completion2 Dec 2022
  4. Study completion2 Dec 2022

Why it stopped: The sponsor finds the risk/benefit analysis unfavorable and has terminated the study.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Model description
Parallel arms with sequential dose escalation
Masking
None (open label)
Enrolment
16 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04025216
Sponsor's protocol ID
CART-TnMUC1-01
Status last verified
Apr 2023
First submitted
12 Jul 2019
Last updated
24 Jan 2024
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing CART-TnMUC1, Cyclophosphamide and Fludarabine in people with Non-Small Cell Lung Cancer and Ovarian Cancer, run by Kite, A Gilead Company at 10 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 20 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 24 Jan 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 10 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: The sponsor finds the risk/benefit analysis unfavorable and has terminated the study.). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Dose Escalation: Dose Identification of CART-TnMUC1 (time frame: Up to 2 years). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04025216.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Jan 2024.

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