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ATL001 in Patients With Advanced Unresectable or Metastatic NSCLC

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ClinicalTrials.gov Identifier: NCT04032847
Recruitment Status : Recruiting
First Posted : July 25, 2019
Last Update Posted : September 20, 2021
Sponsor:
Information provided by (Responsible Party):
Achilles Therapeutics UK Limited

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).

Condition or disease Intervention/treatment Phase
Advanced Non Small Cell Lung Cancer Biological: ATL001 Drug: Pembrolizumab Phase 1 Phase 2

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 be followed up for a period of 24 months post ATL001 infusion in the study. Patients will then be requested to enter a separate long term follow up protocol for a further 5 years (total 84 months)

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 50 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : July 8, 2019
Estimated Primary Completion Date : July 1, 2023
Estimated Study Completion Date : December 31, 2023

Resource links provided by the National Library of Medicine


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




Primary Outcome Measures :
  1. 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


Secondary Outcome Measures :
  1. 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)


Other Outcome Measures:
  1. 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).

  2. 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

  3. 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

  4. 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

  5. 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

  6. 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



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Patient must be at least 18 years old.
  2. Patient must have given written informed consent.
  3. 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. Patient is considered, in the opinion of the investigator, capable of adhering to the protocol.
  10. 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.
  11. Patients must have received a PD-1/ PD-L1 inhibitor prior to treatment with ATL001 (unless contraindicated).

Additional Inclusion Criteria will apply as per the protocol.

Exclusion Criteria:

  1. Patients with evidence of CNS metastases.
  2. Patients with active infectious disease.
  3. Patients who are non-smokers.
  4. Patients requiring immunosuppressive treatments.
  5. Patients requiring regular treatment with systemic steroids.
  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 or non-melanomatous skin cancers).
  11. Patients with a history of organ transplantation.
  12. Patients who have 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 with causal or suspected causal link to immunotherapy.
  15. Patients with a history of ≥ Grade 2 diarrhoea/colitis caused by previous immunotherapy within 6 months of screening. Patients that have been asymptomatic for at least 6 months or have had a normal colonoscopy post-immunotherapy (with uninflamed mucosa by visual assessment) are not excluded.

Additional Exclusion Criteria will apply as per the protocol.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04032847


Contacts
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Contact: Senior VP Clinical Operations Achilles Therapeutics, PhD +44 (0)208 154 4600 info@achillestx.com

Locations
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Sponsors and Collaborators
Achilles Therapeutics UK Limited
Investigators
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Study Director: Medical Monitor, MD Achilles Therapeutics
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Responsible Party: Achilles Therapeutics UK Limited
ClinicalTrials.gov Identifier: NCT04032847    
Other Study ID Numbers: ATX-NS-001
First Posted: July 25, 2019    Key Record Dates
Last Update Posted: September 20, 2021
Last Verified: September 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Pembrolizumab
Antineoplastic Agents, Immunological
Antineoplastic Agents