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
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.
18 Years and up
Accepting Healthy Volunteers?
- 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 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
- 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, catheter associated thrombosis is not included as exclusion criteria.
- Prior 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
Note: Other protocol defined Inclusion/Exclusion criteria may apply.