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

NCT03139370 | Terminated Phase 1 FDA Drug FDA Device

• 2 other identifiers: KITE-718-3012020-005456-37
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 12

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.

Conditions

Solid Tumor

Outcome Measures

Primary Outcomes (2)

• Phase 1A - Percentage of Participants Experiencing Adverse Events Defined as Dose-Limiting Toxicities

  Dose-limiting toxicity is defined as protocol-defined KITE-718 related events with onset within the first 21 days following KITE-718 infusion.

  Up to 21 days

• Phase 1B - Efficacy: Objective Response Rate (ORR)

  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.

  Up to year 2 for solid tumor participants and up to Year 5 for multiple myeloma participants

Secondary Outcomes (7)

• Duration of Response (DOR)

  Up to year 2 for solid tumor participants and up to year 5 for multiple myeloma participants

• Progression-Free Survival (PFS)

  Up to year 2 for solid tumor participants and up to year 5 for multiple myeloma participants

• Overall Survival

  Up to 15 years

• Percentage of Participants Experiencing Adverse Events

  Up to 15 years

• Percentage of Participants with Anti-KITE-718 Antibodies

  Up to 2 years

Study Arms (1)

KITE-718

EXPERIMENTAL

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; Drug: Cyclophosphamide; Drug: Fludarabine; Device: MAGE - A3/A6 Screening Test

Interventions

KITE-718 DRUG

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

KITE-718

Cyclophosphamide DRUG

Administered intravenously

KITE-718

Fludarabine DRUG

Administered intravenously

KITE-718

MAGE - A3/A6 Screening Test DEVICE

A screening test for MAGE-A3/A6+ tumors

KITE-718

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Kite, A Gilead Company: lead

Study Sites (12)

Banner MD Anderson Cancer Center

Gilbert, Arizona, 85234, United States

Location

USC/Norris Comprehensive Cancer Center

Los Angeles, California, 90033, United States

Location

UCLA Hematology/Oncology

Los Angeles, California, 90095, United States

Location

University of California Davis Comprehensive Cancer Center

Sacramento, California, 95817, United States

Location

H. Lee Moffitt Cancer and Research Institute

Tampa, Florida, 33612, United States

Location

University of Chicago

Chicago, Illinois, 60640, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Icahn School of Medicine at Mount Sinai

New York, New York, 10029, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Baylor Scott & White Charles A. Sammons Cancer Center

Dallas, Texas, 75246, United States

Location

The University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

University of Utah, Huntsman Cancer Institute

Salt Lake City, Utah, 84112, United States

Location

Related Links

• Gilead Clinical Trials Website

MeSH Terms

Interventions

Cyclophosphamide; fludarabine

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Study Officials

• Kite Study Director

  Kite, A Gilead Company

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 26, 2017
• First Posted: May 3, 2017
• Study Start: December 27, 2017
• Primary Completion: June 30, 2021
• Study Completion: June 4, 2023
• Last Updated: August 25, 2023

Record last verified: 2023-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (12)