This study will recruit patients with the following cancer indications: ovarian cancer, squamous non-small cell lung cancer, synovial sarcoma and head and neck cancer, with inoperable locally advanced or metastatic solid tumours. Currently, these patients have a poor prognosis and a relatively short overall survival. There is a lack of meaningful, effective therapies available that improve the outcome for these patients. The treatment being investigated in this study is ZIMA4-1, an allogeneic cell therapy product. This is the first time ZI-MA4-1 will be administered to humans. The study is planned to consist of two parts (A and B). Part A includes up to four dose escalation cohorts and aims to identify the maximum tolerated dose of ZI-MA4-1 and give insight into the recommended Phase 2 dose (RP2D). Part B consists of an expansion cohort and is designed to further evaluate the RP2D identified in Part A across one or more indications. The study procedures and eligibility criteria will be the same for participants in Parts A and B, except for the dose level of ZI-MA4-1.
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.
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.
Single group
ZI-MA4-1 (TCR-NK cells)
Biological/VaccineAllogeneic Natural Killer cells transduced with a T cell receptor targeting the tumour-specific melanoma-associated antigen 4 (MAGE-A4)
Cyclophosphamide
DrugLymphodepleting chemotherapy
Fludarabine
DrugLymphodepleting chemotherapy
Safety and tolerability of ZI-MA4-1
Assessed using clinical assessments and adverse event reporting, including dose-limiting toxicities (DLTs), treatment-emergent adverse events (TEAEs), and treatment-related adverse events (TRAEs)
MTD and RP2D of ZI-MA4-1
Identification of maximum tolerated dose (MTD) and the recommended Phase 2 dose (RP2D) of ZI-MA4-1 based on observed DLTs and predefined dose-escalation rules
Long term safety
Evaluate ZI-MA4-1 for the occurrence of delayed adverse events (AEs)
Minimum biologically active dose (MBAD) of ZI-MA4-1
Assessment of preliminary anti-tumour activity
Objective Response Rate (ORR)
Assessed by RECIST 1.1
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