A Study to Test the Safety, Tolerability and Effect of ZI-MA4-1 for Patients With Locally Advanced or Metastatic Solid Malignancies

Prior treatment

• Patients have received any prior cellular or gene therapy.
• Receiving experimental investigational products within 4 weeks of lymphodepletion.
• Recent therapies (within up to 4 weeks prior to lymphodepletion) including biologic agents (such as monoclonal antibodies), anti-cancer immunotherapy (such as monoclonal antibodies against PD-1 receptor or ligand).
• Residual toxicities ≥2 CTCAE grade due to prior therapy, that in the opinion of the investigator may interfere with study conduct.
• Any other active malignancy besides the tumour under study within 3 years prior to screening except for in situ removal of basal cell carcinoma or adequately treated cervix carcinoma in-situ.
• Active fungal, bacterial viral, or other infection requiring intravenous antibiotic, antifungal, or antiviral medication within 7 days prior to lymphodepletion.
• Received or planned to receive a live vaccine ≤6 weeks before the planned start date of lymphodepletion.
• Active bleeding diatheses, including but not limited to therapeutic anticoagulation, and treatment with major surgery within 28 days before lymphodepletion (minor surgical procedures such as lymph node biopsy/excision or catheter placement are permitted).
• Recent treatment with immunosuppressive agents
• Residual toxicities ≥2 Common Terminology Criteria for Adverse Events (CTCAE) grade due to prior therapy, that in the opinion of the investigator may interfere with study conduct Other protocol defined exclusion criteria could apply.

Other illness

• Active or documented history of autoimmune disease or any other diseases requiring immunosuppressive therapy or corticosteroid therapy. Physiological replacement, topical, and inhaled steroids are permitted.
• Significant CNS disorders.
• Myocardial infarction, cardiac angioplasty or stenting, cardiac arrhythmia requiring medication, unstable angina, New York Heart Association Class II or greater congestive heart failure, cardiac atrial or ventricular lymphoma involvement, or other clinically significant cardiac disease within 6 months of enrolment.
• Severe or uncontrolled medical condition (e.g., severe chronic obstructive pulmonary disease, interstitial lung disease , severe Parkinson's disease, active inflammatory bowel disease) or psychiatric condition, which in the opinion of the investigator would interfere with study activities.
• Known significant hepatic or biliary abnormalities. Active infection with hepatitis B, hepatitis C.
• Any medical, psychological, or social condition, drug or alcohol abuse that would make it difficult for the patient to participate in the study and comply with the study procedures, restrictions, and requirements.
• History of allergic reactions to compounds chemically or biologically similar to cyclophosphamide, fludarabine or other agents used in the study
• Medical conditions, such as anti-coagulation, which is not suitable for reversal which, at the opinion of the investigator, preclude or make the patient a poor candidate for biopsy.
• Personal history of allergies or intolerance to local anaesthetic.

Lab values

• QTc \> 450 msec for male participants or \> 470 msec for female participants

Other

• Patients have significant immunosuppression

• HLA-A\*02:01 positive
• Tumour(s) show expression of the MAGE-A4 protein above a defined threshold
• Histopathological or cytological diagnosis of inoperable Locally Advanced or Metastatic malignant disease: ovarian cancer, squamous non-small cell lung cancer (NSCLC), synovial sarcoma or head and neck cancer.
• No approved therapy with demonstrated clinical benefit is indicated or available to treat the patient, or the patient is intolerant of or has refused standard of care therapy.
• Documented imaging confirmed disease progression while on or within 6 months after the end of the most recent therapy.
• Participant must have received ≥2 prior lines of cancer therapy except for patient with synovial sarcoma for whom ≥1 prior lines of cancer therapy.
• Measurable disease according to RECIST v1.1 criteria.
• ECOG performance status of 0 or 1 with no deterioration over the previous 2 weeks, and an anticipated life expectancy of \>3 months
• Female participants are eligible to participate if they are not pregnant or breastfeeding. Woman of childbearing potential must have negative pregnancy test and agree to use an effective contraceptive method.
  • Other protocol defined inclusion criteria could apply.