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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 : Active, not recruiting
First Posted : May 3, 2017
Last Update Posted : September 30, 2021
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences ( Kite, A Gilead Company )

Tracking Information
First Submitted Date  ICMJE April 26, 2017
First Posted Date  ICMJE May 3, 2017
Last Update Posted Date September 30, 2021
Actual Study Start Date  ICMJE May 8, 2017
Estimated Primary Completion Date January 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 30, 2018)
  • 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.
  • 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.
Original Primary Outcome Measures  ICMJE
 (submitted: May 2, 2017)
  • Phase 1A - Safety: Maximum Tolerated Dose [ Time Frame: Up to 5 years ]
    Determine maximum tolerated dose
  • Phase 1B - Efficacy: Objective Response Rate [ Time Frame: Up to 5 years ]
    Evaluate efficacy as per objective response rate
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: February 19, 2021)
  • 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 time from the date of their first objective response to the date of disease progression per modified RECIST v1.1 or consensus panel 1 criteria or death regardless of cause.
  • 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 consensus panel 1 criteria or death from any cause.
  • Overall Survival [ Time Frame: Up to 15 years ]
    Overall survival is defined as the time from KITE-718 infusion to the date of death.
  • Percentage of Participants Experiencing Adverse Events [ Time Frame: Up to 15 years ]
  • Percentage of Participants with Anti-KITE-718 Antibodies [ Time Frame: Up to 2 years ]
  • Percentage of Participants Experiencing Replication-competent Retrovirus (RCR) [ Time Frame: Up to 2 years ]
  • Levels of MAGE-A3/A6 TCR-transduced T Cells in Blood [ Time Frame: Up to 2 years ]
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE 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
Official Title  ICMJE 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
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.
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 Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Solid Tumor
Intervention  ICMJE
  • 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
Study Arms  ICMJE 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.

Interventions:
  • Drug: KITE-718
  • Drug: Cyclophosphamide
  • Drug: Fludarabine
  • Device: MAGE - A3/A6 Screening Test
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: September 29, 2021)
16
Original Estimated Enrollment  ICMJE
 (submitted: May 2, 2017)
50
Estimated Study Completion Date  ICMJE January 2038
Estimated Primary Completion Date January 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Key Inclusion Criteria:

  • Age ≥ 18 years
  • Advanced cancer defined as relapsed or refractory disease after a systemic standard of care treatment regimen and, if available, at least one standard of care salvage regimen unless the subject refuses such therapy. Multiple myeloma (MM) subjects must have had both a protease inhibitor (PI) and immunomodulatory drugs (IMiD) as part of the last regimen, or at least 3 prior lines of therapy, including a PI and an IMiD. Additionally, subjects must not have disease amenable to definitive locoregional therapy.
  • MAGE-A3/A6 positive tumor as confirmed by the central laboratory
  • 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 provided that the definitive therapy was completed more than six months prior to screening.
  • 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 (24-hour urine creatinine clearance is also acceptable)
    • 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 (For ejection fraction only, MUGA scan is also acceptable)
    • 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, catheter associated thrombosis is not included as exclusion criteria.
  • Prior T-cell therapy, including KITE-718 or 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 or Hickman catheter as well as feeding tubes such as a G-tube, 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.

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03139370
Other Study ID Numbers  ICMJE KITE-718-301
Has Data Monitoring Committee No
U.S. FDA-regulated Product
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
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Gilead Sciences ( Kite, A Gilead Company )
Study Sponsor  ICMJE Kite, A Gilead Company
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Kite Study Director Kite, A Gilead Company
PRS Account Gilead Sciences
Verification Date September 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP