Clinical Trials /

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

Description:

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.

Related Conditions:
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: 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: 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

Clinical Trial IDs

  • ORG STUDY ID: KITE-718-301
  • NCT ID: NCT03139370

Conditions

  • Solid Tumor

Interventions

DrugSynonymsArms
KITE-718KITE-718
CyclophosphamideKITE-718
FludarabineKITE-718

Purpose

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.
    

Trial Arms

NameTypeDescriptionInterventions
KITE-718ExperimentalPhase 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.
  • KITE-718
  • Cyclophosphamide
  • Fludarabine

Eligibility Criteria

        Key Inclusion Criteria:

          -  Age ≥ 18 years

          -  Relapsed or refractory disease after a systemic standard of care treatment regimen
             and, if available, at least one standard of care salvage regimen

          -  MAGE-A3/A6 positive tumor

          -  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.

          -  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

               -  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

               -  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

          -  Prior 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 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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Phase 1A - Percentage of Participants Experiencing Adverse Events Defined as Dose-Limiting Toxicities
Time Frame:Up to 21 days
Safety Issue:
Description:Dose-limiting toxicity is defined as protocol-defined KITE-718 related events with onset within the first 21 days following KITE-718 infusion.

Secondary Outcome Measures

Measure:Duration of Response (DOR)
Time Frame:Up to year 2 for solid tumor participants and up to year 5 for multiple myeloma participants
Safety Issue:
Description:For participants who experience an objective response, DOR is defined as the date of their first objective response, which is subsequently confirmed to the date of disease progression per modified RECIST v1.1 or death regardless of cause.
Measure:Progression-Free Survival (PFS)
Time Frame:Up to year 2 for solid tumor participants and up to year 5 for multiple myeloma participants
Safety Issue:
Description:PFS is defined as the time from the KITE-718 infusion date to the date of disease progression per modified RECIST v1.1 or death from any cause.
Measure:Overall Survival
Time Frame:Up to 15 years
Safety Issue:
Description:Overall survival is defined as the time from KITE-718 infusion to the date of death.
Measure:Percentage of Participants Experiencing Adverse Events
Time Frame:Up to 15 years
Safety Issue:
Description:
Measure:Percentage of Participants Experiencing Clinically Significant Changes in Safety Laboratory Values
Time Frame:Up to 15 years
Safety Issue:
Description:
Measure:Percentage of Participants with Anti-KITE-718 Antibodies
Time Frame:Up to 2 years
Safety Issue:
Description:
Measure:Levels of MAGE-A3/A6 TCR-transduced T Cells in Blood
Time Frame:Up to 2 years
Safety Issue:
Description:
Measure:Levels of Cytokines in Serum
Time Frame:Up to 2 years
Safety Issue:
Description:

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Kite, A Gilead Company

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