ATL001 in Patients With Advanced Unresectable or Metastatic NSCLC

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

Detailed Description
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This is a first-in-human, open-label, multi-centre, phase I/IIa study to characterise 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 tumour materials required to manufacture ATL001. Following manufacture of ATL001, the product will be given back to eligible patients following lymphodepletion. 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.

Official Title
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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

Conditions
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Advanced Non Small Cell Lung Cancer

Intervention / Treatment
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* Biological: ATL001
* Drug: Pembrolizumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient must be at least 18 years old. Patient must have given written informed consent. Patients must have confirmed diagnosis of non-small cell lung cancer that is considered to be smoking related. ECOG Performance Status 0-1. Anticipated life expectancy ≥ 6 months at the time of tissue procurement. Measurable disease according to RECIST 1.1 criteria. Adequate organ function per the laboratory parameters defined in the protocol. Patient is considered medically fit to undergo procurement of starting material and ATL001 administration procedures. 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-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. Additional Inclusion Criteria will apply as per the protocol. Exclusion Criteria: Patients with untreated, symptomatic or progressing CNS metastases. Lesions should be clinically and radiologically stable for 2 months after treatment and should not require steroids. Patients with hepatitis B or C, human immunodeficiency virus infection (HIV1/2), syphilis or HTLVI/II infection. Patients requiring immunosuppressive treatments. Patients requiring regular steroids at dose higher than prednisolone 10mg/day (or equivalent). Patients for whom there is documented evidence of an actionable tumour driver oncogene mutation (EGFR, ALK or ROS-1) at the time of initial screening. Patients who have progressed on standard targeted therapies, or for whom no approved targeted treatments are available, are not excluded. Patients with superior vena cava syndrome. Patients with clinically significant, progressive, and/or uncontrolled renal, hepatic, haematological, endocrine, pulmonary, cardiac, gastroenterological or neurological disease. Patients who are pregnant or breastfeeding. Patients who have undergone major surgery in the previous 3 weeks. 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). Patients with a history of organ transplantation. Patients who have previously received any investigational cell or gene therapies. Patients with contraindications for protocol-specified agents. Patients with a history of immune mediated central nervous system toxicity, or a history of ≥ Grade 2 diarrhoea/colitis within the past 6 months caused by previous immunotherapy. Additional Exclusion Criteria will apply as per the protocol.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort A<br>Following lymphodepletion, infusion of cell therapy product ATL001. | Biological: ATL001<br>* ATL001 infusion<br>|
| Experimental: Cohort B<br>Following lymphodepletion, infusion of cell therapy product ATL001 in combination with a checkpoint inhibitor. | Biological: ATL001<br>* ATL001 infusion<br>Drug: Pembrolizumab<br>* Checkpoint inhibitor<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assessment of Treatment Emergent Adverse Events (TEAEs) to evaluate Safety and Tolerability | Evaluate TEAEs and serious AEs, by incidence, severity and relationship to ATL001 | 84 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease Assessment for Change from Baseline in Tumour Size | Evaluate the clinical activity of ATL001 in patients with advanced NSCLC using change from baseline in tumour size at week 6 , week 12 and best overall change from baseline, as assessed by investigator and independent central review (ICR) | Every 6 weeks for 6 months, then every 3 months for a maximum of 84 months |