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
Overview
- Phase
- Phase 1
- Intervention
- ATL001
- Conditions
- Advanced Non Small Cell Lung Cancer
- Sponsor
- Achilles Therapeutics UK Limited
- Enrollment
- 27
- Locations
- 19
- Primary Endpoint
- Assessment of Treatment Emergent Adverse Events (TEAEs) to Evaluate Safety and Tolerability
- Status
- Terminated
- Last Updated
- last year
Overview
Brief Summary
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
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Patient must be at 18-75 years old.
- •Patients must have confirmed diagnosis of non-small cell lung cancer that is considered to be smoking related.
- •Patient is considered medically fit to undergo procurement of starting material and ATL001 administration procedures.
- •ECOG Performance Status 0-
- •Adequate organ function per the laboratory parameters defined in the protocol.
- •Anticipated life expectancy ≥ 6 months at the time of tissue procurement.
- •Measurable disease according to RECIST 1.1 criteria.
- •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 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 requiring immunosuppressive treatments.
- •Patients requiring regular steroids at dose higher than prednisolone 10mg/day (or equivalent)
- •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 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.
- •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
Arms & Interventions
Cohort A
Following lymphodepletion with enhanced host conditioning, infusion of cell therapy product ATL001, followed by a low dose regimen of IL- 2.
Intervention: ATL001
Cohort B
Following lymphodepletion with enhanced host conditioning, infusion of cell therapy product ATL001 in combination with a checkpoint inhibitor, followed by a low dose regimen of IL- 2.
Intervention: ATL001
Cohort B
Following lymphodepletion with enhanced host conditioning, infusion of cell therapy product ATL001 in combination with a checkpoint inhibitor, followed by a low dose regimen of IL- 2.
Intervention: Pembrolizumab
Cohort C
Following lymphodepletion with enhanced host conditioning, infusion of cell therapy product ATL001, followed by a higher dose regimen of IL-2.
Intervention: ATL001
Outcomes
Primary Outcomes
Assessment of Treatment Emergent Adverse Events (TEAEs) to Evaluate Safety and Tolerability
Time Frame: 62 months due to early termination
Evaluate TEAEs and serious AEs, by incidence, severity and relationship to ATL001
Secondary Outcomes
- Disease Assessment for Change From Baseline in Tumour Size(Every 6 weeks for 6 months, then every 3 months for a maximum of 84 months)
- Disease Assessment for Time to Response (TTR) From ATL001 Infusion(Every 6 weeks for 6 months, then every 3 months for a maximum of 84 months)
- Disease Assessment for Objective Response Rate (ORR)(Every 6 weeks for 6 months, then every 3 months (up to 62 months due to early termination))
- Disease Assessment for Duration of Response (DoR). The DoR is Defined as the Time From the Date of First Documented Response Until the Date of Documented Disease Progression or Death(Every 6 weeks for 6 months, then every 3 months for a maximum of 84 months)
- Disease Assessment for Disease Control Rate (DCR)(Every 6 weeks for 6 months, then every 3 months for a maximum of 84 months)
- Disease Assessment for Progression-Free Survival (PFS)(Every 6 weeks for 6 months, then every 3 months for a maximum of 84 months)
- Overall Survival (OS)(Every 6 weeks for 6 months, then every 3 months for a maximum of 84 months)