A Phase 1, Dose-Escalation, Open-Label Study, Evaluating the Safety and Tolerability of ZI-MA4-1, a TCR-NK Cell Therapy, in HLA-A*02:01 Positive Patients With Inoperable, Locally Advanced, or Metastatic MAGE-A4 Expressing Solid Malignancies
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.
• 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.