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: Recruiting
• 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 (Estimated): 50
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Clinical Operations Achilles Therapeutics; Phone Number: +44 (0)20 8154 4600; Email: info@achillestx.com

Study Locations

• France
  • Pierre-Bénite, France, 69310
    • Recruiting
    • Centre Hospitalier Lyon Sud
• Germany
  • Dresden, Germany, 01307
    • Recruiting
    • Universitatsklinikum Carl Gustav Carus Dresden
  • Essen, Germany, 45147
    • Recruiting
    • Universitatsklinikum Essen
• Spain
  • Madrid, Spain, 28040
    • Recruiting
    • Instituto de Investigación Sanitaria Fundación Jimenez Díaz
  • Madrid, Spain, 28050
    • Recruiting
    • Centro Integral Oncologico Clara Campal Hospital Universitario HM Sanchinarro
• United Kingdom
  • Birmingham, United Kingdom, B15 2GW
    • Recruiting
    • University Hospitals Birmingham NHS Foundation Trust, Queen Elizabeth Hospital
  • Cambridge, United Kingdom
    • Recruiting
    • Cambridge University Hospitals NHS Foundation Trust, Addenbrookes Hospital
  • Leeds, United Kingdom, LS9 7TF
    • Recruiting
    • The Leeds Teaching Hospitals NHS Trust, St James's University Hospital
  • London, United Kingdom, NW1 2PG
    • Recruiting
    • University College London Hospitals (UCLH) NHS Foundation Trust, University College Hospital
  • London, United Kingdom, SE19RT
    • Recruiting
    • Guys and St Thomas' NHS Foundation Trust, Guy's Hospital
  • Manchester, United Kingdom, M20 4BX
    • Recruiting
    • The Christie NHS Foundation Trust, Christie Hospital
  • Manchester, United Kingdom, M23 9LT
    • Recruiting
    • Manchester University NHS Foundation Trust, Wythenshawe Hospital
  • Newcastle Upon Tyne, United Kingdom
    • Recruiting
    • The Newcastle upon Tyne Hospitals NHS Foundation Trust, Freeman Hospital
  • Southampton, United Kingdom
    • Recruiting
    • University Hospital Southampton NHS Foundation Trust, Southampton General Hospital
• United States
  • Connecticut
    • New Haven, Connecticut, United States, 06510
      • Recruiting
      • Yale University School of Medicine
  • Florida
    • Tampa, Florida, United States, 33612
      • Recruiting
      • Moffitt Cancer Center
  • New York
    • New York, New York, United States, 10017
      • Recruiting
      • Memorial Sloan Kettering Cancer Center
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Recruiting
      • Duke University Medical 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 least 18 years old.
2. Patient must have given written informed consent.
3. Patients must have 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. 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:

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 requiring immunosuppressive treatments.
4. Patients requiring regular steroids at dose higher than prednisolone 10mg/day (or equivalent).
5. 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.
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 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, early prostate cancer with normal Prostate-Specific Antigen (PSA) or non-melanomatous skin cancers).
11. Patients with a history of organ transplantation.
12. Patients who have previously 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, 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.

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

2

Arms and Interventions

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

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	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

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 (Estimated): July 31, 2025
• Study Completion (Estimated): July 31, 2027

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): September 22, 2023
• Last Update Submitted That Met QC Criteria: September 21, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

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