ATL001 in Patients With Advanced Unresectable or Metastatic NSCLC

NCT04032847 | Terminated Phase 1 Results DMC FDA Drug

• 1 other identifier: ATX-NS-001
• Study Type: interventional
• Target: 27
• Locations: 5 countries
• Sites: 19

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).

Conditions

Advanced Non Small Cell Lung Cancer

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (7)

• 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

Study Arms (3)

Cohort A

EXPERIMENTAL

Following lymphodepletion with enhanced host conditioning, infusion of cell therapy product ATL001, followed by a low dose regimen of IL- 2.

Biological: ATL001

Cohort B

EXPERIMENTAL

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; Drug: Pembrolizumab

Cohort C

EXPERIMENTAL

Following lymphodepletion with enhanced host conditioning, infusion of cell therapy product ATL001, followed by a higher dose regimen of IL-2.

Biological: ATL001

Interventions

ATL001 BIOLOGICAL

ATL001 infusion

Cohort A; Cohort B; Cohort C

Pembrolizumab DRUG

Checkpoint inhibitor

Cohort B

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 0-1.
• 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.

You may not qualify if:

• 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
• Patients who have previously received any investigational cell or gene therapies

Sponsors & Collaborators

• Achilles Therapeutics UK Limited: lead

Study Sites (19)

Yale University School of Medicine

New Haven, Connecticut, 06510, United States

Location

Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10017, United States

Location

Centre Hospitalier Lyon Sud

Pierre-Bénite, 69310, France

Location

Universitätsklinikum Carl Gustav Carus Dresden

Dresden, 01307, Germany

Location

Universitätsklinikum Essen

Essen, 45147, Germany

Location

Hospital Clinic de Barcelona

Barcelona, Catalonia, 08036, Spain

Location

Instituto de Investigación Sanitaria Fundación Jimenez Díaz

Madrid, 28040, Spain

Location

Centro Integral Oncologico Clara Campal Hospital Universitario HM Sanchinarro

Madrid, 28050, Spain

Location

Hospital Clinico Universitario de Valencia

Valencia, 46010, Spain

Location

University Hospitals Birmingham NHS Foundation Trust, Queen Elizabeth Hospital

Birmingham, B15 2GW, United Kingdom

Location

Cambridge University Hospitals NHS Foundation Trust, Addenbrookes Hospital

Cambridge, United Kingdom

Location

The Leeds Teaching Hospitals NHS Trust, St James's University Hospital

Leeds, LS9 7TF, United Kingdom

Location

University College London Hospitals (UCLH) NHS Foundation Trust, University College Hospital

London, NW1 2PG, United Kingdom

Location

Guys and St Thomas' NHS Foundation Trust, Guy's Hospital

London, SE19RT, United Kingdom

Location

The Christie NHS Foundation Trust, Christie Hospital

Manchester, M20 4BX, United Kingdom

Location

Manchester University NHS Foundation Trust, Wythenshawe Hospital

Manchester, M23 9LT, United Kingdom

Location

The Newcastle upon Tyne Hospitals NHS Foundation Trust, Freeman Hospital

Newcastle upon Tyne, United Kingdom

Location

University Hospital Southampton NHS Foundation Trust, Southampton General Hospital

Southampton, United Kingdom

Location

MeSH Terms

Interventions

pembrolizumab

Results Point of Contact

• Title: Dr Matilde Saggese
• Organization: Achilles Therapeutics UK Limited

matildesaggese@gmail.com

0786 9814607

Study Officials

• Medical Monitor, MD

  Achilles Therapeutics

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 17, 2019
• First Posted: July 25, 2019
• Study Start: July 8, 2019
• Primary Completion: September 26, 2024
• Study Completion: September 26, 2024
• Last Updated: March 10, 2025
• Results First Posted: March 10, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (3); DE (2); GB (9); FR (1); ES (4)