ATL001 in Patients With Advanced Unresectable or Metastatic NSCLC

• ClinicalTrials.gov Identifier: NCT04032847
• Recruitment Status: Recruiting
• First Posted: July 25, 2019
• Last Update Posted: May 16, 2024
• Sponsor: Achilles Therapeutics UK Limited
• Information provided by (Responsible Party): Achilles Therapeutics UK Limited

Tracking Information

• First Submitted Date: July 17, 2019
• First Posted Date: July 25, 2019
• Last Update Posted Date: May 16, 2024
• Actual Study Start Date: July 8, 2019
• Estimated Primary Completion Date: July 31, 2025 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: September 6, 2021)

Assessment of Treatment Emergent Adverse Events (TEAEs) to evaluate Safety and Tolerability [ Time Frame: 84 months ]

Evaluate TEAEs and serious AEs, by incidence, severity and relationship to ATL001

Original Primary Outcome Measures (submitted: July 22, 2019)

Assessment of Treatment Emergent Adverse Events to evaluate Safety and Tolerability [ Time Frame: 84 months ]

Evaluate treatment-emergent adverse events (TEAEs) and serious AEs, per CTCAE, by incidence, severity and relationship to ATL001

Current Secondary Outcome Measures (submitted: July 22, 2019)

Disease Assessment for Change from Baseline in Tumour Size [ Time Frame: 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)

• Original Secondary Outcome Measures: Same as current

Current Other Pre-specified Outcome Measures (submitted: September 6, 2021)

• Disease Assessment for Objective Response Rate (ORR) [ Time Frame: Every 6 weeks for 6 months, then every 3 months for a maximum of 84 months ]
  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).
• Disease Assessment for Time to Response (TTR) from ATL001 infusion [ Time Frame: 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 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 [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: Every 6 weeks for 6 months, then every 3 months for a maximum of 84 months ]
  Evaluate OS by the investigator

Original Other Pre-specified Outcome Measures (submitted: July 22, 2019)

• Disease Assessment for Objective Response Rate [ Time Frame: Every 6 weeks for 6 months, then every 3 months for a maximum of 84 months ]
  Evaluate the endpoint of objective 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).
• Disease Assessment for Time to Response from ATL001 infusion [ Time Frame: Every 6 weeks for 6 months, then every 3 months for a maximum of 84 months ]
  Evaluate the endpoint of time to response by the investigator and ICR, per RECIST v1.1 and im-RECIST
• 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 [ Time Frame: Every 6 weeks for 6 months, then every 3 months for a maximum of 84 months ]
  Evaluate the endpoint of duration of response (DOR) by the investigator and ICR, per RECIST v1.1 and im-RECIST
• Disease Assessment for Disease Control Rate [ Time Frame: Every 6 weeks for 6 months, then every 3 months for a maximum of 84 months ]
  Evaluate the endpoints of disease control rate (DCR) as assessed by the the investigator and ICR per RECIST v1.1 and im-RECIST
• Disease Assessment for Progression-Free Survival [ Time Frame: Every 6 weeks for 6 months, then every 3 months for a maximum of 84 months ]
  Evaluate the efficacy endpoints of progression-free survival (PFS) as assessed by the investigator and ICR per RECIST v1.1 and im-RECIST
• Overall Survival [ Time Frame: Every 6 weeks for 6 months, then every 3 months for a maximum of 84 months ]
  Evaluate overall survival (OS) by the investigator

Descriptive Information

• Brief Title: ATL001 in Patients With Advanced Unresectable or Metastatic NSCLC
• 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
• 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 Type: Interventional
• Study Phase: Phase 1; Phase 2
• Study Design: Allocation: Non-Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Advanced Non Small Cell Lung Cancer

Intervention

• Biological: ATL001
  ATL001 infusion
• Drug: Pembrolizumab
  Checkpoint inhibitor

Study Arms

• Experimental: Cohort A
  Following lymphodepletion with enhanced host conditioning, infusion of cell therapy product ATL001, followed by a low dose regimen of IL- 2.
  Intervention: Biological: ATL001
• 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.
  Interventions:

  • Biological: ATL001
  • Drug: Pembrolizumab
• Experimental: Cohort C
  Following lymphodepletion with enhanced host conditioning, infusion of cell therapy product ATL001, followed by a higher dose regimen of IL-2.
  Intervention: Biological: ATL001

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: July 22, 2019): 50
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: July 31, 2027
• Estimated Primary Completion Date: July 31, 2025 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 75 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Achilles Therapeutics UK Limited; +44 (0)20 8154 4600; Clinical.info@achillestx.com

• Listed Location Countries: France, Germany, Spain, United Kingdom, United States

Administrative Information

• NCT Number: NCT04032847
• Other Study ID Numbers: ATX-NS-001
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Achilles Therapeutics UK Limited
• Original Responsible Party: Same as current
• Current Study Sponsor: Achilles Therapeutics UK Limited
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Medical Monitor, MD; Achilles Therapeutics

• PRS Account: Achilles Therapeutics UK Limited
• Verification Date: May 2024