Try the modernized beta website. Learn more about the modernization effort.
Working… Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT03139370
Recruitment Status : Active, not recruiting
First Posted : May 3, 2017
Last Update Posted : April 6, 2022
Information provided by (Responsible Party):
Gilead Sciences ( Kite, A Gilead Company )

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. Subjects who received an infusion of KITE-718 will complete the remainder of the 15 year follow-up assessments in a separate long-term follow-up study, KT-US-982-5968

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 16 participants
Allocation: N/A
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 : December 27, 2017
Actual Primary Completion Date : June 30, 2021
Estimated Study Completion Date : October 2022

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

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 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.

  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 consensus panel 1 criteria 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 with Anti-KITE-718 Antibodies [ Time Frame: Up to 2 years ]
  6. Percentage of Participants Experiencing Replication-competent Retrovirus (RCR) [ Time Frame: Up to 2 years ]
  7. Levels of MAGE-A3/A6 TCR-transduced T Cells in Blood [ Time Frame: Up to 2 years ]

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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

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.

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 identifier (NCT number): NCT03139370

Layout table for location information
United States, Arizona
Banner MD Anderson Cancer Center
Gilbert, Arizona, United States, 85234
United States, California
USC/Norris Comprehensive Cancer Center
Los Angeles, California, United States, 90033
UCLA Hematology/Oncology
Los Angeles, California, United States, 90095
University of California Davis Comprehensive Cancer Center
Sacramento, California, United States, 95817
United States, Florida
H. Lee Moffitt Cancer and Research Institute
Tampa, Florida, United States, 33612
United States, Illinois
University of Chicago
Chicago, Illinois, United States, 60640
United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
United States, New York
Icahn School of Medicine at Mount Sinai
New York, New York, United States, 10029
Memorial Sloan Kettering Cancer Center
New York, New York, United States, 10065
United States, Texas
Baylor Scott & White Charles A. Sammons Cancer Center
Dallas, Texas, United States, 75246
The University of Texas MD Anderson Cancer Center
Houston, Texas, United States, 77030
United States, Utah
University of Utah, Huntsman Cancer Institute
Salt Lake City, Utah, United States, 84112
Sponsors and Collaborators
Kite, A Gilead Company
Layout table for investigator information
Study Director: Kite Study Director Kite, A Gilead Company
Additional Information:
Layout table for additonal information
Responsible Party: Kite, A Gilead Company Identifier: NCT03139370    
Other Study ID Numbers: KITE-718-301
First Posted: May 3, 2017    Key Record Dates
Last Update Posted: April 6, 2022
Last Verified: April 2022

Layout table for additional information
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
Additional relevant MeSH terms:
Layout table for MeSH terms
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists