ATL001 in Patients With Advanced Unresectable or Metastatic NSCLC

Advanced Non Small Cell Lung Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04032847
• Other study ID #: ATX-NS-001
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: July 8, 2019
• Est. completion date: July 31, 2027

Study information

• Verified date: May 2024
• Source: Achilles Therapeutics UK Limited
• Contact: Achilles Therapeutics UK Limited
• Phone: +44 (0)20 8154 4600
• Email: Clinical.info[@]achillestx.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 50
• Est. completion date: July 31, 2027
• Est. primary completion date: July 31, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Advanced Non Small Cell Lung Cancer
• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms

Intervention

Biological:
• ATL001
ATL001 infusion

Drug:
• Pembrolizumab
Checkpoint inhibitor

Locations

Country	Name	City	State
France	Centre Hospitalier Lyon Sud	Pierre-Bénite
Germany	Universitätsklinikum Carl Gustav Carus Dresden	Dresden
Germany	Universitätsklinikum Essen	Essen
Spain	Hospital Clinic de Barcelona	Barcelona	Catalonia
Spain	Centro Integral Oncologico Clara Campal Hospital Universitario HM Sanchinarro	Madrid
Spain	Instituto de Investigación Sanitaria Fundación Jimenez Díaz	Madrid
Spain	Hospital Clinico Universitario de Valencia	Valencia
United Kingdom	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	Guys and St Thomas' NHS Foundation Trust, Guy's Hospital	London
United Kingdom	University College London Hospitals (UCLH) NHS Foundation Trust, University College Hospital	London
United Kingdom	Manchester University NHS Foundation Trust, Wythenshawe Hospital	Manchester
United Kingdom	The Christie NHS Foundation Trust, Christie 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 States	Duke University Medical Center	Durham	North Carolina
United States	Yale University School of Medicine	New Haven	Connecticut
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	Moffitt Cancer Center	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Achilles Therapeutics UK Limited

Countries where clinical trial is conducted

United States,  France,  Germany,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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
Other	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
Other	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	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
Other	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
Other	Overall Survival (OS)	Evaluate OS by the investigator	Every 6 weeks for 6 months, then every 3 months for a maximum of 84 months
Primary	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	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