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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
9
Allogeneic Natural Killer cells transduced with a T cell receptor targeting the tumour-specific melanoma-associated antigen 4 (MAGE-A4)
Lymphodepleting chemotherapy
Lymphodepleting chemotherapy
The Royal Marsden NHS Foundation Trust
London, United Kingdom
NOT_YET_RECRUITINGThe Christie NHS Foundation Trust
Manchester, United Kingdom
RECRUITINGSafety 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)
Time frame: From baseline through end of study visit (up to 5 years)
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
Time frame: Through completion of study response follow-up (up to 2 years)
Long term safety
Evaluate ZI-MA4-1 for the occurrence of delayed adverse events (AEs)
Time frame: Through end of study visit (up to 5 years)
Minimum biologically active dose (MBAD) of ZI-MA4-1
Assessment of preliminary anti-tumour activity
Time frame: Through completion of study response follow-up (up to 2 years)
Objective Response Rate (ORR)
Assessed by RECIST 1.1
Time frame: Through completion of study response follow-up (up to 2 years)
Best Overall Response (BOR)
Assessed by RECIST 1.1
Time frame: Through completion of study response follow-up (up to 2 years)
Disease Control Rate (DCR)
Assessed by RECIST 1.1
Time frame: Through completion of study response follow-up (up to 2 years)
Pharmacokinetics of ZI-MA4-1
Evaluation of persistence of ZI-MA4-1 cells in the blood using vector copy number (VCN) analysis
Time frame: 3 years post-infusion of ZI-MA4-1
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.