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Safety and Efficacy of MAGE-A3/A6 T Cell Receptor Engineered T Cells (KITE-718) in HLA-DPB1*04:01 Positive Adults With Advanced Cancers

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ClinicalTrials.gov Identifier: NCT03139370
Recruitment Status : Recruiting
First Posted : May 3, 2017
Last Update Posted : July 2, 2019
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences ( Kite, A Gilead Company )

Study Description
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Brief Summary:
The primary objectives of Phase 1A are to evaluate the safety of KITE-718, determine a recommended Phase 1B dose, and to evaluate the efficacy of KITE-718 in Phase 1B.

Condition or disease Intervention/treatment Phase
Solid Tumor Drug: KITE-718 Drug: Cyclophosphamide Drug: Fludarabine Device: MAGE - A3/A6 Screening Test Phase 1

Detailed Description:
Participants found to be human leukocyte antigen (HLA)-DPB1*04:01 positive and whose tumors are MAGE-A3 and/or MAGE-A6 positive can participate if all eligibility criteria are met. Other tests required to determine eligibility include a physical exam, electrocardiogram (ECG) and echocardiogram (ECHO) of the heart, CT or MRI scans, and blood draws. Eligible participants have white blood cells collected by leukapheresis. These cells are genetically modified to make the experimental treatment KITE-718. The desired outcome is that the genetically modified T cells will target tumor cells that express MAGE-A3 and/or MAGE-A6, which are proteins that can be expressed by cancer cells. Participants receive chemotherapy prior to the KITE-718 infusion. After the KITE-718 infusion, participants will be followed for side effects and have scans performed to see any potential impact on their cancers. Study procedures may be performed while hospitalized and/or in the outpatient setting.

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 75 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1 Study Evaluating the Safety and Efficacy of MAGE-A3/A6 T Cell Receptor Engineered T Cells (KITE-718) in HLA-DPB1*04:01 Positive Subjects With Advanced Cancers
Actual Study Start Date : May 8, 2017
Estimated Primary Completion Date : June 2021
Estimated Study Completion Date : March 2036
Arms and Interventions
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Arm Intervention/treatment
Experimental: KITE-718

Phase 1A: Participants will receive cyclophosphamide and fludarabine conditioning chemotherapy followed by the investigational treatment, KITE-718.

Phase 1 B: Participants will receive cyclophosphamide and fludarabine conditioning chemotherapy followed by the investigational treatment, KITE-718, at a dose selected based on Phase 1A.

 Drug: KITE-718
A single infusion of autologous genetically modified MAGE-A3/A6 T-cell receptor (TCR) transduced autologous T cells (KITE-718).

Drug: Cyclophosphamide
Administered intravenously

Drug: Fludarabine
Administered intravenously

Device: MAGE - A3/A6 Screening Test
A screening test for MAGE-A3/A6+ tumors


Outcome Measures
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Primary Outcome Measures :
  1. Phase 1A - Percentage of Participants Experiencing Adverse Events Defined as Dose-Limiting Toxicities [ Time Frame: Up to 21 days ]
    Dose-limiting toxicity is defined as protocol-defined KITE-718 related events with onset within the first 21 days following KITE-718 infusion.

  2. Phase 1B - Efficacy: Objective Response Rate (ORR) [ Time Frame: Up to year 2 for solid tumor participants and up to Year 5 for multiple myeloma participants ]
    ORR is defined as complete response + partial response for participants evaluated by RECIST v1.1 and very good partial response (VGPR) or better for multiple myeloma participants evaluated by International Myeloma Working Group (IMWG) Consensus Panel 1 Criteria.


Secondary Outcome Measures :
  1. Duration of Response (DOR) [ Time Frame: Up to year 2 for solid tumor participants and up to year 5 for multiple myeloma participants ]
    For participants who experience an objective response, DOR is defined as the date of their first objective response, which is subsequently confirmed to the date of disease progression per modified RECIST v1.1 or death regardless of cause.

  2. Progression-Free Survival (PFS) [ Time Frame: Up to year 2 for solid tumor participants and up to year 5 for multiple myeloma participants ]
    PFS is defined as the time from the KITE-718 infusion date to the date of disease progression per modified RECIST v1.1 or death from any cause.

  3. Overall Survival [ Time Frame: Up to 15 years ]
    Overall survival is defined as the time from KITE-718 infusion to the date of death.

  4. Percentage of Participants Experiencing Adverse Events [ Time Frame: Up to 15 years ]
  5. Percentage of Participants Experiencing Clinically Significant Changes in Safety Laboratory Values [ Time Frame: Up to 15 years ]
  6. Percentage of Participants with Anti-KITE-718 Antibodies [ Time Frame: Up to 2 years ]
  7. Levels of MAGE-A3/A6 TCR-transduced T Cells in Blood [ Time Frame: Up to 2 years ]
  8. Levels of Cytokines in Serum [ Time Frame: Up to 2 years ]

Eligibility Criteria
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Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Key Inclusion Criteria:

  • Age ≥ 18 years
  • Relapsed or refractory disease after a systemic standard of care treatment regimen and, if available, at least one standard of care salvage regimen
  • MAGE-A3/A6 positive tumor
  • HLA-DPB1*04:01 positive
  • At least 1 measurable lesion on CT or MRI
  • No evidence of central nervous system (CNS) disease by MRI or CT of the brain. Note: Prior brain metastasis which have been treated with definitive therapy are eligible.
  • Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
  • Toxicities due to prior therapy must be recovered to baseline or ≤ grade 1, except for clinically non-significant toxicities such as alopecia

  • Adequate bone marrow function as evidenced by:

    • Absolute neutrophil count (ANC) ≥ 1000/mm^3
    • Platelet ≥ 100/mm^3
    • Hemoglobin > 8 g/dL

  • Adequate renal, hepatic, cardiac, and pulmonary function as evidenced by:

    • Creatinine clearance (as estimated by Cockcroft Gault) ≥ 60 cc/min
    • Alanine transaminase (ALT)/aspartate aminotransferase (AST) ≤ 2.5 x upper limit normal (ULN) or ≤ 5 x ULN if documented liver metastases
    • Total bilirubin ≤ 1.5 mg/dL
    • Cardiac ejection fraction ≥ 50%, no evidence of pericardial effusion as determined by an ECHO, and no clinically significant ECG findings
    • No clinically significant pleural effusion
    • Baseline oxygen saturation > 92% on room air

Key Exclusion Criteria:

  • Malignancy other than non-melanoma skin cancer, carcinoma in situ, or low grade prostate cancer for which watch-and-wait approach is standard of care, unless disease free for at least 3 years
  • Clinically significant cardiac disease within last 12 months
  • Stroke or transient ischemic attack (TIA) within 12 last months
  • Symptomatic deep vein thrombosis or pulmonary embolism within last 6 months
  • Prior MAGE-A3/A6-targeting therapy
  • Live vaccine ≤ 4 weeks prior to enrollment
  • Systemic corticosteroid therapy within 7 days before enrollment.
  • History of severe, immediate hypersensitivity reaction attributed to aminoglycosides
  • Presence of fungal, bacterial, viral, or other infection requiring IV antimicrobials for management.
  • Presence of any indwelling line or drain. Note: Dedicated central venous access catheters such as a Port-a-Cath are permitted.
  • Primary immunodeficiency
  • Autoimmune disease resulting in end-organ injury or requiring systemic immunosuppression/systemic disease modifying agents within the last 2 years prior to enrollment
  • Known history of infection with HIV, hepatitis B (HBsAg positive), or hepatitis C (anti-HCV positive). A history of treated hepatitis B or hepatitis C is permitted if the viral load is undetectable per quantitative polymerase chain reaction (PCR) and/or nucleic acid testing.
  • Females who are pregnant as confirmed by a positive serum or urine pregnancy test or are breastfeeding.
  • Individuals of both genders of child-bearing potential who are not willing to practice birth control from the time of consent through 6 months after the completion of KITE-718

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03139370


Contacts
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Contact: Medical Information 1-844-454-5483(1-844-454-KITE) medinfo@kitepharma.com

Locations
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United States, California
USC/Norris Comprehensive Cancer Center Recruiting
Los Angeles, California, United States, 90033
Contact: Jessica Levano, RN    323-865-0593    Jessica.Levano@med.usc.edu   
Principal Investigator: David Quinn, MD         
UCLA Hematology/Oncology Recruiting
Los Angeles, California, United States, 90095
Contact: Anna Crosetti       ACrosetti@mednet.ucla.edu   
Principal Investigator: Alexandra Drakaki, MD         
University of California Davis Comprehensive Cancer Center Recruiting
Sacramento, California, United States, 95817
Contact: Steffany Lim    916-734-0561    sllim@ucdavis.edu   
Principal Investigator: Mehrdad Abedi, MD         
United States, Florida
University of Miami Hospital and Clinics, Sylvester Comprehensive Cancer Center Recruiting
Miami, Florida, United States, 33136
Contact: Weiwen Wang    305-243-2122    wwang1@med.miami.edu   
Principal Investigator: Peter Hosein, MD         
H. Lee Moffitt Cancer and Research Institute Recruiting
Tampa, Florida, United States, 12902
Contact: Jeffrey Edelman       jeffrey.edelman@moffitt.org   
Principal Investigator: Benjamin Creelan, MD         
United States, Massachusetts
Massachusetts General Hospital Recruiting
Boston, Massachusetts, United States, 02114
Contact: Jami Brown    617-724-9190    jbrown56@mgh.harvard.edu   
Principal Investigator: Marcela Maus, MD, PhD         
United States, New York
Icahn School of Medicine at Mount Sinai Recruiting
New York, New York, United States, 10029
Contact: Cynthia Knauer, RN    212-241-9955    Cynthia.knauer@mountsinai.org   
Contact: Ash Tewari, MD    1-212-241-9955    Ash.tewari@mountsinai.org   
Principal Investigator: Ash Tewari, MD         
Memorial Sloan Kettering Cancer Center Recruiting
New York, New York, United States, 10065
Contact: Geoffrey Noah    646-888-4593      
Contact: Shanette Bourne    646-888-4593      
Principal Investigator: Chris Klebanoff, MD         
United States, Texas
Baylor Scott & White Charles A. Sammons Cancer Center Recruiting
Dallas, Texas, United States, 75246
Contact: Carlos Becerra, MD    214-370-1254    carlos.becerra@usoncology.com   
Contact: Sophia Macabare    214-818-7198    SOPHIA.MACABARE@BSWHEALTH.ORG   
Principal Investigator: Carlos Becerra, MD         
The University of Texas MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact: Ly Nguyen    713-563-2169    lmnguyen1@mdanderson.org   
Principal Investigator: Partow Kebriaei, MD         
Sponsors and Collaborators
Kite, A Gilead Company
Investigators
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Study Director: Kite Study Director Kite, A Gilead Company
More Information
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Responsible Party: Kite, A Gilead Company
ClinicalTrials.gov Identifier: NCT03139370     History of Changes
Other Study ID Numbers: KITE-718-301
First Posted: May 3, 2017    Key Record Dates
Last Update Posted: July 2, 2019
Last Verified: July 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: Yes
Device Product Not Approved or Cleared by U.S. FDA: Yes
Pediatric Postmarket Surveillance of a Device Product: No
Additional relevant MeSH terms:
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Cyclophosphamide
Fludarabine
Fludarabine phosphate
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
 Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antimetabolites, Antineoplastic
Antimetabolites