An open-label, multi-centre, phase I/IIa study evaluating the safety and clinical activity of neoantigen reactive T cells in patients with metastatic or recurrent melanoma. - ATX-ME-001 - ATL001 for the Treatment of Metastatic or Recurrent Melanoma

Achilles Therapeutics UK Limited0 个研究点目标入组 40 人开始时间: 2022年7月4日最近更新: 2024年5月6日

试验速览

阶段: 1 期
状态: 进行中（未招募）
发起方: Achilles Therapeutics UK Limited
入组人数: 40

研究概览入排标准研究者记录与标识符相似试验

研究概览

简要总结

暂无简介。

研究设计

研究类型: Interventional

入排标准

性别: All

入选标准

•Inclusion criteria will apply at multiple timepoints.
•Inclusion Criteria:
•1. Patient must be at least 18 years old at the screening visit.
•2. Patient must have given written informed consent to participate in the study.
•3. Patients must have histologically confirmed diagnosis of melanoma.
•4. Patients must have received a PD-1/PD-L1 inhibitor prior to treatment with ATL001 (unless contraindicated).
•5. Patients whose tumour is known to have a BRAF V600 mutation must have received BRAF targeted therapy (as well as a PD-1/PD-L1 inhibitor unless contraindicated) prior to treatment with ATL001.
•6. Patient is considered medically fit enough to undergo all study procedures and interventions: procedures to procure blood and tumour tissue, including a general anaesthetic if required, and to receive fludarabine, cyclophosphamide and IL-2 at protocol doses and schedules.
•7. Patient is considered, in the opinion of the Investigator, capable of adhering to the protocol.
•8. Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1.
•9. Adequate organ function indicated by the following laboratory parameters:
•a. Haemoglobin = 10.0 g/dL.
•b. White Blood Cell Count (WBC) = 3.0 x10^9/L.
•c. Absolute Neutrophil Count (ANC) = 1.5 x10^9/L.
•d. Platelets = 100 x10^9/L.
•e. INR/PT and APTR/APTT < 1.5x ULN, unless receiving therapeutic anticoagulation. Investigator discretion is required to ensure surgery is safe or that anticoagulants can be safely stopped.
•f. AST or ALT = 2.5x ULN.
•g. Bilirubin < 1.5x ULN (or < 3x ULN if Gilbert’s Syndrome).
•h. Creatinine clearance/estimated glomerular filtration rate (GFR) = 50 mL/min.
•10. Female patients who are of childbearing potential must agree to use a highly effective method of contraception during the study and for at least 12 months after the ATL001 infusion. Non-sterilised male participants who intend to be sexually active with a female partner of childbearing potential must use an acceptable method of contraception from the time of screening, throughout the duration of the study and for at least 6 months after the ATL001 infusion. Refer to Appendix G for pregnancy testing requirements in Germany. See Section 4.3 for details of acceptable methods of contraception.
•In addition to a re-evaluation of criteria 1-10, the following inclusion criteria must also be met prior to tissue procurement:
•11. To be eligible to enter this study for procurement, the patient must fall into one of the following groups:
•a) Patients with metastatic or recurrent disease who have had no prior systemic therapy for advanced disease and who have accessible sites of disease suitable for collection of adequate tissue for ATL001 manufacture.
•b) Patients with metastatic or recurrent disease who are on or have completed first line systemic therapy and have accessible sites of disease suitable for collection of adequate tissue for ATL001 manufacture.
•c) Other patients with advance stage disease for whom no other alternative approved treatments are available, may be considered on a case-by-case basis and should be discussed with the Sponsor prior to enrolment.
•12. Anticipated life expectancy = 6 months at the time of tissue procurement.
•In addition to a re-evaluation of criteria 1-10, the following inclusion criteria must also be met prior to lymphodepletion for treatment with ATL001:
•13. Patients must have metastatic melanoma and:
•a. Whose disease has progressed or recurred following standard of care. This includes patients who have received a

排除标准

•Exclusion criteria will apply at multiple timepoints.
•Exclusion Criteria:
•1. Patients with known leptomeningeal disease or central nervous system (CNS) metastases that are untreated or symptomatic or progressing. Lesions should be clinically and radiologically stable for 2 months after treatment, as determined by MRI or CT evaluation, in line with accepted standard of care procedures, and should not require steroids.
•2. Patients with ocular, acral or mucosal melanoma.
•3. Patients with hepatitis B or C, human immunodeficiency virus infection (HIV1/2), syphilis or HTLVI/II infection (see Section 6.1.1).
•4. Patients with active, known, or suspected autoimmune disease requiring immunosuppressive treatments.
•5. Patients requiring regular treatment with steroids at a dose higher than prednisolone 10 mg/day (or equivalent).
•6. Patients with a current or recent history, as determined by the Investigator, of clinically significant, progressive, and/or uncontrolled renal, hepatic, haematological, endocrine, pulmonary, cardiac, gastroenterological or neurological disease.
•7. Patients with a history of immune mediated central nervous system toxicity that was caused by, or suspected to be caused by, immunotherapy.
•8. Patients with a history of = Grade 2 diarrhoea/colitis caused by previous immunotherapy within 6 months of screening. Patients that have been asymptomatic for at least 6 months or have had a normal colonoscopy postimmunotherapy (with uninflamed mucosa by visual assessment following discontinuation of immune suppression other than permitted modified release steroids) are not excluded.
•9. Patients who are pregnant or breastfeeding.
•10. Patients who have undergone major surgery in the previous 3 weeks.
•11. Patients with an active concurrent cancer or a history of cancer within the past 3 years (except for in situ carcinomas, early prostate cancer with normal Prostate-Specific Antigen (PSA) or non-melanomatous skin cancers).
•12. Patients with a history of organ transplantation.
•13. Patients who have previously received any investigational cell or gene therapies.
•14. Patients with contraindications for cyclophosphamide, fludarabine and IL-2 at per protocol doses (see Investigator’s Brochure for details).
•15. Patients with a confirmed history of allergic reactions to amphotericin b, penicillin and/or streptomycin.
•In addition to 1-15, the following exclusion criteria apply to patients who have received anti-cancer therapy prior to study entry:
•16. Patients who have received any cytotoxic chemotherapy within the 3 weeks prior to tissue and blood procurement.
•In addition, the following exclusion criteria will apply for eligibility for Cohort B:
•17. Patients with a history of (non-infectious) pneumonitis that required systemic steroids, or current pneumonitis/interstitial lung disease.
•18. Patients with a history of severe hypersensitivity to a monoclonal antibody, allergy or hypersensitivity to nivolumab itself and/or its components.
•19. Patients who have received a live vaccination within the 28 days prior to the first dose of nivolumab.
•20. Patients with any contraindications for nivolumab (Refer to the latest available prescribing information (e.g. SmPC/Package Insert) for reference safety information for nivolumab).
•In addition, the following exclusion criteria will apply prior to lymphodepletion for eligibility for Cohort C:
•21. Patients with a Left Ventricular Ejection Fraction (LVEF) < 45%.
•22. Patients with a forced expiratory volume

研究者

发起方

Achilles Therapeutics UK Limited

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