ATL001 in Patients With Metastatic or Recurrent Melanoma

This is a first-in-human, open-label, multi-centre, phase I/IIa study to characterize the safety and clinical activity of ATL001, autologous clonal neoantigen reactive T cells (cNeT) administered intravenously in adults with metastatic or recurrent melanoma.

This is a first-in-human, open-label, multi-centre, phase I/IIa study to characterize the safety and clinical activity autologous clonal neoantigen reactive T cells (cNeT) administered intravenously in adults with metastatic or recurrent melanoma.

Patients will initially enter the study for procurement of tumour materials required to manufacture ATL001.Following manufacture of ATL001, the product will be given back to eligible patients following lymphodepletion.

Patients will be followed up for a period of 24 months post ATL001 infusion in the study.

Patients will continue to be followed up for a minimum of 5 years, as part of a separate Long Term Follow Up Protocol, or, if the separate protocol is not available at the study site, within this protocol.

Eligibility Criteria:
Inclusion Criteria:

1. Patient must be at least 18 years old.
2. Patient must have given written informed consent.
3. Patients must have histologically confirmed diagnosis of melanoma.
4. Patient is considered medically fit to undergo procurement of starting material and ATL001 administration procedures.
5. ECOG Performance Status 0-1.
6. Adequate organ function per the laboratory parameters defined in the protocol.
7. Female patients who are of childbearing potential must agree to use a highly effective method of contraception during the study 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.
8. Anticipated life expectancy ≥ 6 months at the time of tissue procurement.
9. Measurable disease according to RECIST v1.1 criteria. Additional inclusion criteria will apply as per the study protocol.

Exclusion Criteria:

1. Patients with known leptomeningeal disease or untreated, symptomatic or progressing central nervous system (CNS) metastases. Lesions should be clinically and radiologically stable for 2 months after treatment and should not require steroids.
2. Patients with ocular, acral or mucosal melanoma.
3. Patients with hepatitis B or C, human immunodeficiency virus infection (HIV 1/2), syphilis or HTLV I/II infection.
4. Patients requiring immunosuppressive treatments.
5. Patients requiring regular steroids at a dose higher than prednisolone 10mg/day (or equivalent).
6. Patients with clinically significant, progressive, and/or uncontrolled renal, hepatic, haematological, endocrine, pulmonary, cardiac, gastroenterological, or neurological disease.
7. Patients with a history of immune mediated (CNS) toxicity or ≥ Grade 2 diarrhoea/colitis caused by, , previous immunotherapy within the past 6 months.
8. Patients who are pregnant or breastfeeding.
9. Patients who have undergone major surgery in the previous 3 weeks.
10. 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).
11. Patients with a history of organ transplantation.
12. Patients who have previously received any investigational cell or gene therapies.
13. Patients with contraindications for protocol specified agents.

Additional Exclusion criteria will apply as per the study protocol.