ATL001 in Patients With Advanced Unresectable or Metastatic NSCLC

Phase 1

Terminated

• Conditions: Advanced Non Small Cell Lung Cancer
• Interventions: Biological: ATL001; Drug: Pembrolizumab

• Registration Number: NCT04032847
• Lead Sponsor: Achilles Therapeutics UK Limited

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.

Study Timeline

• Study Start: 2019-07-08
• Study First Submitted: 2019-07-17
• Study First Submitted QC: 2019-07-22
• Study First Posted: 2019-07-25
• Primary Completion: 2024-09-26
• Study Completion: 2024-09-26
• Status Verified: 2025-02
• Results First Submitted: 2025-02-05
• Results First Submitted QC: 2025-02-25
• Last Update Submitted: 2025-02-25
• Results First Posted: 2025-03-10
• Last Update Posted: 2025-03-10

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 27

Inclusion Criteria

1. Patient must be at 18-75 years old.
2. Patients must have confirmed diagnosis of non-small cell lung cancer that is considered to be smoking related.
3. Patient is considered medically fit to undergo procurement of starting material and ATL001 administration procedures.
4. ECOG Performance Status 0-1.
5. Adequate organ function per the laboratory parameters defined in the protocol.
6. Anticipated life expectancy ≥ 6 months at the time of tissue procurement.
7. Measurable disease according to RECIST 1.1 criteria.

Additional Inclusion Criteria will apply as per the protocol.

Exclusion Criteria

1. 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.
2. Patients with hepatitis B or C, human immunodeficiency virus infection (HIV1/2), syphilis or HTLVI/II infection.
3. 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.
4. Patients requiring immunosuppressive treatments.
5. Patients requiring regular steroids at dose higher than prednisolone 10mg/day (or equivalent)
6. Patients with superior vena cava syndrome.
7. Patients with clinically significant, progressive, and/or uncontrolled renal, hepatic, haematological, endocrine, pulmonary, cardiac, gastroenterological or neurological disease.
8. 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.
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 Prostate- Specific Antigen (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

Additional Exclusion Criteria will apply as per the protocol.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Cohort A	ATL001	Following lymphodepletion with enhanced host conditioning, infusion of cell therapy product ATL001, followed by a low dose regimen of IL- 2.
Cohort B	ATL001	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.
Cohort B	Pembrolizumab	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.
Cohort C	ATL001	Following lymphodepletion with enhanced host conditioning, infusion of cell therapy product ATL001, followed by a higher dose regimen of IL-2.

Primary Outcome Measures

Name	Time	Method
Assessment of Treatment Emergent Adverse Events (TEAEs) to Evaluate Safety and Tolerability	62 months due to early termination	Evaluate TEAEs and serious AEs, by incidence, severity and relationship to ATL001

Secondary Outcome Measures

Name	Time	Method
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	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)
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	Evaluate the endpoint of TTR by the investigator and ICR, per RECIST v1.1 and im-RECIST
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)	Evaluate the endpoint of overall response rate (ORR), as assessed by investigator and ICR, per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 and immune modified RECIST( im-RECIST).; RECIST v1.1 (Response Evaluation Criteria in Solid Tumors) is a standardized system for measuring tumor response to treatment in clinical trials. Tumors are assessed by imaging (e.g., CT or MRI) based on changes in size. Responses are categorized as: Complete Response (CR): Disappearance of all target lesions. Partial Response (PR): ≥30% reduction in the sum of target lesions. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for Progressive Disease (PD).; Progressive Disease (PD): ≥20% increase in the sum of target lesions, or appearance of new lesions.; These criteria help assess the efficacy of treatments in solid tumors supported by im-RECIST in immunotherapy.
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	Evaluate the endpoint of DOR by the investigator and ICR, per RECIST v1.1 and im-RECIST
Disease Assessment for Disease Control Rate (DCR)	Every 6 weeks for 6 months, then every 3 months for a maximum of 84 months	Evaluate the endpoints of DCR as assessed by the investigator and ICR per RECIST v1.1 and im-RECIST
Disease Assessment for Progression-Free Survival (PFS)	Every 6 weeks for 6 months, then every 3 months for a maximum of 84 months	Evaluate the efficacy endpoints of PFS as assessed by the investigator and ICR per RECIST v1.1 and im-RECIST
Overall Survival (OS)	Every 6 weeks for 6 months, then every 3 months for a maximum of 84 months	Evaluate OS by the investigator

Trial Locations

Locations (19)

Yale University School of Medicine; 🇺🇸 New Haven, Connecticut, United States

Moffitt Cancer Center; 🇺🇸 Tampa, Florida, United States

Memorial Sloan Kettering Cancer Center; 🇺🇸 New York, New York, United States

Centre Hospitalier Lyon Sud; 🇫🇷 Pierre-Bénite, France

Universitätsklinikum Carl Gustav Carus Dresden; 🇩🇪 Dresden, Germany

Universitätsklinikum Essen; 🇩🇪 Essen, Germany

Hospital Clinic de Barcelona; 🇪🇸 Barcelona, Catalonia, Spain

Instituto de Investigación Sanitaria Fundación Jimenez Díaz; 🇪🇸 Madrid, Spain

Centro Integral Oncologico Clara Campal Hospital Universitario HM Sanchinarro; 🇪🇸 Madrid, Spain

Hospital Clinico Universitario de Valencia; 🇪🇸 Valencia, Spain

University Hospitals Birmingham NHS Foundation Trust, Queen Elizabeth Hospital; 🇬🇧 Birmingham, United Kingdom

Cambridge University Hospitals NHS Foundation Trust, Addenbrookes Hospital; 🇬🇧 Cambridge, United Kingdom

The Leeds Teaching Hospitals NHS Trust, St James's University Hospital; 🇬🇧 Leeds, United Kingdom

University College London Hospitals (UCLH) NHS Foundation Trust, University College Hospital; 🇬🇧 London, United Kingdom

Guys and St Thomas' NHS Foundation Trust, Guy's Hospital; 🇬🇧 London, United Kingdom

The Christie NHS Foundation Trust, Christie Hospital; 🇬🇧 Manchester, United Kingdom

Manchester University NHS Foundation Trust, Wythenshawe Hospital; 🇬🇧 Manchester, United Kingdom

The Newcastle upon Tyne Hospitals NHS Foundation Trust, Freeman Hospital; 🇬🇧 Newcastle Upon Tyne, United Kingdom

University Hospital Southampton NHS Foundation Trust, Southampton General Hospital; 🇬🇧 Southampton, United Kingdom