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| ID | Type | Description | Link |
|---|---|---|---|
| ISRCTN14753723 | Registry Identifier | ISRCTN registry |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| ZI-MA4-1 (TCR-NK cells) | Experimental | Participants receive ZI-MA4-1 administered via IV infusion 3 times per treatment cycle at their assigned dose. It is planned that all participants in the study will get a minimum of one treatment cycle and up to a maximum of two treatment cycles. Prior to a treatment cycle, a participant is given fludarabine and cyclophosphamide to temporarily reduce lymphocytes in the body (lymphodepletion). |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| ZI-MA4-1 (TCR-NK cells) | Biological | Allogeneic Natural Killer cells transduced with a T cell receptor targeting the tumour-specific melanoma-associated antigen 4 (MAGE-A4) |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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) | From baseline through end of study visit (up to 5 years) |
| Measure | Description | Time Frame |
|---|---|---|
| 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 | Through completion of study response follow-up (up to 2 years) |
| Long term safety |
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Inclusion Criteria:
Other protocol defined inclusion criteria could apply.
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Zelluna Immunotherapy | Contact | +47 413 80 080 | ctinfo@zelluna.com |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| The Royal Marsden NHS Foundation Trust | Not yet recruiting | London | United Kingdom |
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| Cyclophosphamide | Drug | Lymphodepleting chemotherapy |
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| Fludarabine | Drug | Lymphodepleting chemotherapy |
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Evaluate ZI-MA4-1 for the occurrence of delayed adverse events (AEs) |
| Through end of study visit (up to 5 years) |
| Minimum biologically active dose (MBAD) of ZI-MA4-1 | Assessment of preliminary anti-tumour activity | Through completion of study response follow-up (up to 2 years) |
| Objective Response Rate (ORR) | Assessed by RECIST 1.1 | Through completion of study response follow-up (up to 2 years) |
| Best Overall Response (BOR) | Assessed by RECIST 1.1 | Through completion of study response follow-up (up to 2 years) |
| Disease Control Rate (DCR) | Assessed by RECIST 1.1 | 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 | 3 years post-infusion of ZI-MA4-1 |
| The Christie NHS Foundation Trust | Recruiting | Manchester | United Kingdom |
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| ID | Term |
|---|---|
| D010051 | Ovarian Neoplasms |
| D013584 | Sarcoma, Synovial |
| D006258 | Head and Neck Neoplasms |
| ID | Term |
|---|---|
| D004701 | Endocrine Gland Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D010049 | Ovarian Diseases |
| D000291 | Adnexal Diseases |
| D005831 | Genital Diseases, Female |
| D052776 | Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D005833 | Genital Neoplasms, Female |
| D014565 | Urogenital Neoplasms |
| D000091662 | Genital Diseases |
| D004700 | Endocrine System Diseases |
| D006058 | Gonadal Disorders |
| D009372 | Neoplasms, Connective Tissue |
| D018204 | Neoplasms, Connective and Soft Tissue |
| D009370 | Neoplasms by Histologic Type |
| D012509 | Sarcoma |
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| ID | Term |
|---|---|
| D003520 | Cyclophosphamide |
| C024352 | fludarabine |
| ID | Term |
|---|---|
| D010752 | Phosphoramide Mustards |
| D009588 | Nitrogen Mustard Compounds |
| D009150 | Mustard Compounds |
| D006846 | Hydrocarbons, Halogenated |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D063088 | Phosphoramides |
| D009943 | Organophosphorus Compounds |
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