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

NCT ID: NCT03139370

Last Updated: 2023-08-25

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 16 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-12-27
• Study Completion Date: 2023-06-04

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. 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

Conditions

Solid Tumor

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

KITE-718

Intervention Type: DRUG

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

Cyclophosphamide

Intervention Type: DRUG

Administered intravenously

Fludarabine

Intervention Type: DRUG

Administered intravenously

MAGE - A3/A6 Screening Test

Intervention Type: DEVICE

A screening test for MAGE-A3/A6+ tumors

Interventions

KITE-718

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

Intervention Type: DRUG

Cyclophosphamide

Administered intravenously

Intervention Type: DRUG

Fludarabine

Administered intravenously

Intervention Type: DRUG

MAGE - A3/A6 Screening Test

A screening test for MAGE-A3/A6+ tumors

Intervention Type: DEVICE

Eligibility Criteria

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

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
• 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Kite, A Gilead Company

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Kite Study Director

Role: STUDY_DIRECTOR

Kite, A Gilead Company

Locations

Banner MD Anderson Cancer Center

Gilbert, Arizona, United States

USC/Norris Comprehensive Cancer Center

Los Angeles, California, United States

UCLA Hematology/Oncology

Los Angeles, California, United States

University of California Davis Comprehensive Cancer Center

Sacramento, California, United States

H. Lee Moffitt Cancer and Research Institute

Tampa, Florida, United States

University of Chicago

Chicago, Illinois, United States

Massachusetts General Hospital

Boston, Massachusetts, United States

Icahn School of Medicine at Mount Sinai

New York, New York, United States

Memorial Sloan Kettering Cancer Center

New York, New York, United States

Baylor Scott & White Charles A. Sammons Cancer Center

Dallas, Texas, United States

The University of Texas MD Anderson Cancer Center

Houston, Texas, United States

University of Utah, Huntsman Cancer Institute

Salt Lake City, Utah, United States

Countries

United States

Related Links

https://www.gileadclinicaltrials.com/study/?id=KITE-718-301

Gilead Clinical Trials Website

Other Identifiers

2020-005456-37

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

KITE-718-301

Identifier Type: -

Identifier Source: org_study_id