Solid Tumor
Conditions
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
Interventions
DRUGKITE-718
A single infusion of autologous genetically modified MAGE-A3/A6 T-cell receptor (TCR) transduced autologous T cells (KITE-718).
DRUGCyclophosphamide
Administered intravenously
DRUGFludarabine
Administered intravenously
DEVICEMAGE - A3/A6 Screening Test
A screening test for MAGE-A3/A6+ tumors
Sponsors
Kite, A Gilead Company
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Phase 1A - Percentage of Participants Experiencing Adverse Events Defined as Dose-Limiting Toxicities | 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) | 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
| Measure | Time frame | Description |
|---|---|---|
| Duration of Response (DOR) | 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) | 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 | 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 | Up to 15 years | — |
| Percentage of Participants with Anti-KITE-718 Antibodies | Up to 2 years | — |
| Percentage of Participants Experiencing Replication-competent Retrovirus (RCR) | Up to 2 years | — |
| Levels of MAGE-A3/A6 TCR-transduced T Cells in Blood | Up to 2 years | — |
Countries
United States
Outcome results
None listed