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: A 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
  • 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

Purpose

Participants who are HLA-DPB1*04:01 positive and whose tumors are MAGE-A3/A6 positive may be eligible for this study. If eligible, white blood cells are collected by apheresis and genetically modified to recognize cancer cells which express MAGE-A3/A6. Chemotherapy precedes infusion of the genetically modified cells. Participants may be hospitalized and/or return to the study doctor for check-ups and medical evaluations. The purpose of the study is to see if the treatment is safe and effective in treating advanced cancer.

Detailed Description

      Participants found to be be 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, ECG and 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
MAGE-A3/A6 and HLA-DPB1*04:01 Positive SubjectsExperimentalPhase 1A - dose escalation. Phase 1B - enrolled by tumor type

    Eligibility Criteria

            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 CNS disease by MRI or CT of the brain. Note: Prior brain metastasis
                 which have been treated with definitive therapy are eligible.
    
              -  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:
    
                   -  ANC ≥ 1000/mm3
    
                   -  Platelet ≥ 100/mm3
    
                   -  Hemoglobin > 8 g/dL
    
              -  Adequate renal, hepatic, cardiac, and pulmonary function as evidenced by:
    
                   -  Creatinine clearance (as estimated by Cockcroft Gault) ≥ 60 cc/min
    
                   -  ALT/AST ≤ 2.5 x 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
    
            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 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 PCR and/or nucleic acid testing.
    
              -  Females who are pregnant as confirmed by a positive serum or urine pregnancy test or
                 are breastfeeding.
    
              -  Subjects 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
          
    Maximum Eligible Age:N/A
    Minimum Eligible Age:18 Years
    Eligible Gender:All
    Healthy Volunteers:No

    Primary Outcome Measures

    Measure:Phase 1A - Safety: Maximum Tolerated Dose
    Time Frame:Up to 5 years
    Safety Issue:
    Description:Determine maximum tolerated dose

    Details

    Phase:Phase 1
    Primary Purpose:Interventional
    Overall Status:Recruiting
    Lead Sponsor:Kite Pharma, Inc.

    Last Updated

    May 5, 2017