ATL001 in Patients With Advanced Unresectable or Metastatic NSCLC

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 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).

Study Overview

• Status: Terminated
• Conditions: Advanced Non Small Cell Lung Cancer
• Intervention / Treatment: Biological: ATL001; Drug: Pembrolizumab

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 Type: Interventional
• Enrollment (Actual): 27
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• France
  • Pierre-Bénite, France, 69310
    • Centre Hospitalier Lyon Sud
• Germany
  • Dresden, Germany, 01307
    • Universitätsklinikum Carl Gustav Carus Dresden
  • Essen, Germany, 45147
    • Universitätsklinikum Essen
• Spain
  • Madrid, Spain, 28040
    • Instituto de Investigación Sanitaria Fundación Jimenez Díaz
  • Madrid, Spain, 28050
    • Centro Integral Oncologico Clara Campal Hospital Universitario HM Sanchinarro
  • Valencia, Spain, 46010
    • Hospital Clinico Universitario de Valencia
  • Catalonia
    • Barcelona, Catalonia, Spain, 08036
      • Hospital Clinic De Barcelona
• United Kingdom
  • Birmingham, United Kingdom, B15 2GW
    • University Hospitals Birmingham NHS Foundation Trust, Queen Elizabeth Hospital
  • Cambridge, United Kingdom
    • Cambridge University Hospitals NHS Foundation Trust, Addenbrookes Hospital
  • Leeds, United Kingdom, LS9 7TF
    • The Leeds Teaching Hospitals NHS Trust, St James's University Hospital
  • London, United Kingdom, NW1 2PG
    • University College London Hospitals (UCLH) NHS Foundation Trust, University College Hospital
  • London, United Kingdom, SE19RT
    • Guys and St Thomas' NHS Foundation Trust, Guy's Hospital
  • Manchester, United Kingdom, M23 9LT
    • Manchester University NHS Foundation Trust, Wythenshawe Hospital
  • Manchester, United Kingdom, M20 4BX
    • The Christie NHS Foundation Trust, Christie Hospital
  • Newcastle Upon Tyne, United Kingdom
    • The Newcastle upon Tyne Hospitals NHS Foundation Trust, Freeman Hospital
  • Southampton, United Kingdom
    • University Hospital Southampton NHS Foundation Trust, Southampton General Hospital
• United States
  • Connecticut
    • New Haven, Connecticut, United States, 06510
      • Yale University School of Medicine
  • Florida
    • Tampa, Florida, United States, 33612
      • Moffitt Cancer Center
  • New York
    • New York, New York, United States, 10017
      • Memorial Sloan Kettering Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort A; Following lymphodepletion with enhanced host conditioning, infusion of cell therapy product ATL001, followed by a low dose regimen of IL- 2.	Biological: ATL001; ATL001 infusion
Experimental: 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.	Biological: ATL001; ATL001 infusion; Drug: Pembrolizumab; Checkpoint inhibitor
Experimental: Cohort C; Following lymphodepletion with enhanced host conditioning, infusion of cell therapy product ATL001, followed by a higher dose regimen of IL-2.	Biological: ATL001; ATL001 infusion

What is the study measuring?

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	62 months due to early termination

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease Assessment for Disease Control Rate (DCR)	Evaluate the endpoints of DCR as assessed by the investigator and ICR per RECIST v1.1 and im-RECIST	Every 6 weeks for 6 months, then every 3 months for a maximum of 84 months
Disease Assessment for Progression-Free Survival (PFS)	Evaluate the efficacy endpoints of PFS as assessed by the investigator and ICR per RECIST v1.1 and im-RECIST	Every 6 weeks for 6 months, then every 3 months for a maximum of 84 months
Overall Survival (OS)	Evaluate OS by the investigator	Every 6 weeks for 6 months, then every 3 months for a maximum of 84 months
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
Disease Assessment for Time to Response (TTR) From ATL001 Infusion	Evaluate the endpoint of TTR by the investigator and ICR, per RECIST v1.1 and im-RECIST	Every 6 weeks for 6 months, then every 3 months for a maximum of 84 months
Disease Assessment for Objective Response Rate (ORR)	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.	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	Evaluate the endpoint of DOR by the investigator and ICR, per RECIST v1.1 and im-RECIST	Every 6 weeks for 6 months, then every 3 months for a maximum of 84 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease Assessment for Objective Response Rate (ORR)	Evaluate the endpoint of ORR as assessed by investigator and ICR, per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 and immune modified RECIST( im-RECIST).	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	Evaluate the endpoint of TTR by the investigator and ICR, per RECIST v1.1 and im-RECIST	Every 6 weeks for 6 months, then every 3 months for a maximum of 84 months
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	Evaluate the endpoint of DOR by the investigator and ICR, per RECIST v1.1 and im-RECIST	Every 6 weeks for 6 months, then every 3 months for a maximum of 84 months
Disease Assessment for Disease Control Rate (DCR)	Evaluate the endpoints of DCR as assessed by the investigator and ICR per RECIST v1.1 and im-RECIST	Every 6 weeks for 6 months, then every 3 months for a maximum of 84 months
Disease Assessment for Progression-Free Survival (PFS)	Evaluate the efficacy endpoints of PFS as assessed by the investigator and ICR per RECIST v1.1 and im-RECIST	Every 6 weeks for 6 months, then every 3 months for a maximum of 84 months
Overall Survival (OS)	Evaluate OS by the investigator	Every 6 weeks for 6 months, then every 3 months for a maximum of 84 months

Collaborators and Investigators

• Sponsor: Achilles Therapeutics UK Limited
• Investigators: Study Director: Medical Monitor, MD, Achilles Therapeutics

Study record dates

Study Major Dates

• Study Start (Actual): July 8, 2019
• Primary Completion (Actual): September 26, 2024
• Study Completion (Actual): September 26, 2024

Study Registration Dates

• First Submitted: July 17, 2019
• First Submitted That Met QC Criteria: July 22, 2019
• First Posted (Actual): July 25, 2019

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 25, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Pembrolizumab
• Other Study ID Numbers: ATX-NS-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No