An Open-Label, Multi-Centre Phase I/IIa Study Evaluating the Safety and Clinical Activity of Neoantigen Reactive T Cells in Patients With Advanced Non-Small Cell Lung Cancer

This is a first-in-human, open-label, multi-centre, phase I/IIa study to characterize the safety and clinical activity of autologous clonal neoantigen reactive T cells (cNeT) administered intravenously in adults with advanced non-small cell lung cancer (NSCLC).

Patients will initially enter the study for procurement of tumor 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 then be requested to enter a separate long term follow up protocol for a further 5 years (total 84 months)

Inclusion Criteria:

1. Patient must be at least 18 years old.
2. Patient must have given written informed consent.
3. Confirmed diagnosis of non-small cell lung cancer that is considered to be smoking related.
4. ECOG Performance status 0-1
5. Anticipated life expectancy ≥ 6 months at the time of tissue procurement.
6. Measurable disease according to RECIST 1.1 criteria.
7. Adequate organ function per the laboratory parameters defined in the protocol.
8. Patient is considered medically fit to undergo procurement of starting material and ATL001 administration procedures.
9. Patient is considered, in the opinion of the investigator, capable of adhering to the protocol.
10. 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, and for at least 4 months after the last dose of pembrolizumab. Non-sterilized 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.
11. Patients must have received a PD-1/ PD-L1 inhibitor prior to treatment with ATL001 (unless contraindicated).

Additional Inclusion Criteria will apply as per the protocol.

Exclusion Criteria:

1. Patients with evidence of CNS metastases.
2. Patients with active infectious disease.
3. Patients who are non-smokers.
4. Patients requiring immunosuppressive treatments.
5. Patients requiring regular treatment with systemic steroids.
6. Patients with superior vena cava syndrome.
7. Patients with clinically significant, progressive, and/or uncontrolled renal, hepatic, hematological, endocrine, pulmonary, cardiac, gastroenterological or neurological disease.
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 or non-melanomatous skin cancers).
11. Patients with a history of organ transplantation.
12. Patients who have received any investigational cell or gene therapies.
13. Patients with contraindications for protocol specified agents.
14. Patients with a history of immune mediated central nervous system toxicity with causal or suspected causal link to immunotherapy.
15. Patients with a history of ≥ Grade 2 diarrhea/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 post-immunotherapy (with uninflamed mucosa by visual assessment) are not excluded.