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

September 1, 2026 updated by: Zelluna Immunotherapy AS

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

9

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • United Kingdom
      • London, United Kingdom
        • Recruiting
        • The Royal Marsden NHS Foundation Trust
        • Contact:
          • Dr. Furness
      • Manchester, United Kingdom
        • Recruiting
        • The Christie NHS Foundation Trust
        • Contact:
          • Prof. Thistlethwaite

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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 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.
  • 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.
  • 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.
  • 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).
  • Patients have significant immunosuppression
  • 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
  • QTc > 450 msec for male participants or > 470 msec for female participants
  • 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.
  • 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: ZI-MA4-1 (TCR-NK cells)
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).
Drug: Cyclophosphamide
Lymphodepleting chemotherapy
Drug: Fludarabine
Lymphodepleting chemotherapy
Biological: ZI-MA4-1 (TCR-NK cells)
Allogeneic Natural Killer cells transduced with a T cell receptor targeting the tumour-specific melanoma-associated antigen 4 (MAGE-A4)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Safety and tolerability of ZI-MA4-1
Time Frame: From baseline through end of study visit (up to 5 years)
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)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
MTD and RP2D of ZI-MA4-1
Time Frame: Through completion of study response follow-up (up to 2 years)
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
Time Frame: Through end of study visit (up to 5 years)
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
Time Frame: Through completion of study response follow-up (up to 2 years)
Assessment of preliminary anti-tumour activity
Through completion of study response follow-up (up to 2 years)
Objective Response Rate (ORR)
Time Frame: Through completion of study response follow-up (up to 2 years)
Assessed by RECIST 1.1
Through completion of study response follow-up (up to 2 years)
Best Overall Response (BOR)
Time Frame: Through completion of study response follow-up (up to 2 years)
Assessed by RECIST 1.1
Through completion of study response follow-up (up to 2 years)
Disease Control Rate (DCR)
Time Frame: Through completion of study response follow-up (up to 2 years)
Assessed by RECIST 1.1
Through completion of study response follow-up (up to 2 years)
Pharmacokinetics of ZI-MA4-1
Time Frame: 3 years post-infusion 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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Zelluna Immunotherapy AS

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 11, 2026

Primary Completion (Estimated)

December 1, 2028

Study Completion (Estimated)

December 1, 2032

Study Registration Dates

First Submitted

May 15, 2026

First Submitted That Met QC Criteria

May 21, 2026

First Posted (Actual)

May 29, 2026

Study Record Updates

Last Update Posted (Actual)

September 4, 2026

Last Update Submitted That Met QC Criteria

September 1, 2026

Last Verified

September 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ZIMA-101
  • ISRCTN14753723 (Registry Identifier: ISRCTN registry)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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