Ovarian cancer, squamous non-small-cell lung cancer, synovial sarcoma, head and neck cancer. Cancer
Conditions
Interventions
This is an open-label, first-in-human, Phase 1 dose-escalation study (3+3 design) evaluating the safety and tolerability of ZI-MA4-1, an allogeneic TCR-NK cell therapy, in patients with advanced solid
Sponsors
Zelluna Immunotherapy AS
Eligibility
Sex/Gender
All
Age
18 Years to 75 Years
Inclusion criteria
Inclusion criteria: Pre-Screening Inclusion Criteria 1. Participant has signed the Pre-Screening ICF 2. Participant is HLA-A*02:01 positive (assessed by the hospital’s own laboratory vendor) 3. Participant’s tumour(s) show expression of the MAGE-A4 protein of =30% tumour cells at =2+ intensity (assessed by sponsors central lab) 4. Participant meets, or is expected to comply with all Screening Inclusion Criteria Screening Inclusion Criteria (Part A and Part B) 5. Participant must be capable of giving signed informed consent as described in Section 10.3 which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol. 6. 18 to =75 years of age, at the time of signing the informed consent. 7. 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. 8. No approved therapy with demonstrated clinical benefit is indicated or available to treat the patients, or the patient is intolerant of or has refused standard of care therapy. Patients should not have been withdrawn from any treatment (considered necessary for the clinical management of the patient) with the only purpose being fulfilling the study eligibility criteria. 9. Patients must have documented imaging confirmed disease progression while on or within 6 months after the end of the most recent therapy. 10. Patients must have received =2 prior lines of cancer therapy except for patient with synovial sarcoma for whom =1 prior lines of cancer therapy are required. 11. Patients have measurable disease according to RECIST v1.1 criteria. 12. An ECOG PS of 0 or 1 with no deterioration over the previous 2 weeks, and an anticipated life expectancy of >3 months following lymphodepletion. 13. Adequate haematological, renal, and hepatic function within 7 days of the start of lymphodepletion 14. Patients must not have evidence of rapidly progressive disease that would preclude patient from completing at least 1 cycle of ZI-MA4-1 treatment. The lymphodepletion regimen comprises cyclophosphamide and fludarabine which are teratogenic and may impair fertility, appropriate contraception and pregnancy precautions are required. Contraceptive guidance is consistent with the respective Summaries of Product Characteristics (SmPCs) for cyclophosphamide and fludarabine. Contraceptive use by participants or participants’ partners should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies 15. Female participants are eligible to participate if they are not pregnant or breastfeeding, and one of the following conditions applies: o Participant is a woman of non-childbearing potential (WONCBP) as defined in Section 13.1.1 OR o WOCBP must have negative pregnancy test and agree to use a highly effective contraceptive method Note: Breastfeeding is prohibited during treatment and for at least 6 months following the last dose of ZI-MA4-1. See Section 8.3.5 for pregnancy testing schedule. The investigator should evaluate the potential for contraceptive method failure (e.g., noncompliance, recently initiated). 16. A WOCBP must have a negative hCG serum pregnancy test at screening and a negative urine/serum pregnancy test within 24 hours of lymphodepletion (requirements for pregnancy testing during and after the study are provided in Section 8.3.5). o
Exclusion criteria
Exclusion criteria: Pre-Screening Exclusion Criteria 1. Participant currently meets, or is expected to meet, any of the Main Exclusion Criteria. Screening Exclusion Criteria (Part A and Part B) 1. Patients have received any prior cellular or gene therapy. 2. Receiving experimental investigational products within 4 weeks of lymphodepletion. 3. Recent therapies prior to lymphodepletion including: a. Within 4 weeks or 5 half-lives (whichever is longer) of the start of lymphodepletion: biologic agents (such as monoclonal antibodies including marketed drugs), anti-cancer immunotherapy including monoclonal antibodies against PD-1 receptor or ligand. b. Within 4 weeks of lymphodepletion: Bone/soft tissue directed palliative radiotherapy, c. Within 3 weeks of lymphodepletion: Cytotoxic chemotherapy or loco-regional therapy, liver directed radiation therapy within 3 months. d. Within 2 weeks of lymphodepletion: Systemic corticosteroids, other types of radiotherapy not stated above, or any other immunosuppressive therapy. e. Any other therapy, which in the opinion of the investigator presents as a contra indication to lymphodepletion. f. Treatment with biologic agents (such as monoclonal antibodies including marketed drugs) within 4 weeks or 5 half-lives (whichever is longer) of the start of lymphodepletion in this study. 4. Residual toxicities =2 CTCAE grade due to prior therapy, that in the opinion of the investigator may interfere with study conduct. 5. Patients have had 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. 6. Active or documented history of autoimmune disease or any other diseases requiring immunosuppressive therapy or corticosteroid therapy (defined as >10 mg/day prednisone or equivalent). Physiological replacement, topical, and inhaled steroids are permitted. 7. Significant CNS disorders including Uncontrolled seizures and CNS metastases, within 3 months of enrolment. 8. 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. 9. Active fungal, bacterial viral, or other infection requiring intravenous antibiotic, antifungal, or antiviral medication within 7 days prior to lymphodepletion, including acute symptoms of COVID-19 infection or positive covid test. 10. Received or planned to receive a live vaccine =6 weeks before the planned start date of lymphodepletion. 11. 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. 12. 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). 13. Patients have significant immunosuppression 14. Known significant hepatic or biliary abnormalities. Active infection with hepatitis B (HbsAg positive), hepatitis C (anti-HCV positive). A history of hepatitis B or hepatitis C is permitted
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Safety and tolerability of ZI-MA4-1 from baseline through end of study visit measured using clinical assessments and adverse event reporting recorded in the eCRF, including dose-limiting toxicities (DLTs), treatment-emergent adverse events (TEAEs), and treatment-related adverse events (TRAEs), assessed at baseline through Day 28 and throughout the study up to 5 years | — |
Countries
England, United Kingdom
Contacts
Public ContactMedical and Product Information Enquiry .
Outcome results
None listed