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 (THETIS)

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. Histologically confirmed diagnosis of melanoma. 4. Patients must have received a PD-1 inhibitor prior to treatment with ATL001. 5. Patients whose tumour is known to have a BRAF V600 mutation must have received BRAF targeted therapy (as well as a PD-1 inhibitor) 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. 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 x10⁹/L. c. Absolute Neutrophil count (ANC) > = 1.5 x 10⁹/L. d. Platelets > = 100 x 10⁹/L. e. PT and APTT < 1.5 x ULN (unless receiving therapeutic anticoagulation). f. AST or ALT < = 2.5 x ULN. g. Bilirubin < 1.5 x ULN (or < 3 x ULN in Gilbert’s Syndrome). h. Creatinine clearance/estimated 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. Patients with female partners of childbearing potential must agree to use adequate contraception for at least 6 months after the ATL001 infusion. See Section 4.3 of the protocol for details of acceptable methods of contraception. In addition to 1-10, the following inclusion criteria must be met prior to tissue procurement: 11.To be eligible for this study a patient must fall into one of the following groups: a) Patients with unresectable metastatic disease (newly diagnosed or recurrent) who have had no prior systemic therapy for advanced disease and who have accessible sites of disease suitable collection of adequate tissue for ATL001 manufacture. b) Patients with high risk locally advanced resectable disease (i.e. palpable Stage III) who are scheduled to undergo surgery. These patients are not candidates for immediate treatment with ATL001 but may be treated in this protocol if the disease recurs. In these patients the tumour samples will be stored in compliance with the appropriate regulations to enable future manufacture and treatment with ATL001. c) Patients with unresectable metastatic 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. d) Other patients with unresectable advanced 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 1-10, the following inclusion criteria must be met prior to lymphodepletion and treatment with ATL001: 13. Patients must have measurable disease according to RECIST v1.1 criteria prior to lymphodepletion. (If patients have no measurable disease following standard therapy, lymphodepletion and ATL001 treatment may be delayed until there is evidence of measurable disease). 14. Patient is considered well enough to receive ATL001 treatment.

Exclusion criteria will apply at multiple timepoints. Exclusion criteria: 1. Patients with known leptomeningeal disease or CNS metastases. 2. Patients with ocular melanoma. 3. Patients with hepatitis B or C, human immunodeficiency virus infection (HIV1/2), syphilis or HTLVI/II infection. 4. Patients with active autoimmune disease requiring immunosuppressive therapy. 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 who are pregnant or breastfeeding. 8. Patients who have undergone major surgery in the previous 3 weeks. 9. 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 PSA or non-melanomatous skin cancers). 10. Patients with a history of organ transplantation. 11. Patients who have previously received any investigational cell or gene therapies. 12. Patients with contraindications for cyclophosphamide, fludarabine and IL-2 at per protocol doses (see Investigator Brochure for details). In addition to 1-12, the following exclusion criteria apply to patients who completed first line therapy prior to study entry: 13. Patients who have received any anti-cancer therapy within the 3 weeks prior to blood and tumour tissue procurement. In addition to 1-12, the following exclusion criteria apply to all patients prior to lymphodepletion and treatment with ATL001: 14. Patients who have received a live vaccination within the 28 days prior to lymphodepletion. 15. Patients with an active infection requiring antibiotics. 16. Patients who have received any anti-cancer therapy within the 3 weeks prior to lymphodepletion.