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ATL001 in Patients With Metastatic or Recurrent Melanoma

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ClinicalTrials.gov Identifier: NCT03997474
Recruitment Status : Recruiting
First Posted : June 25, 2019
Last Update Posted : January 9, 2023
Sponsor:
Information provided by (Responsible Party):
Achilles Therapeutics UK Limited

Study Description
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Brief Summary:
This is a first-in-human, open-label, multi-centre, phase I/IIa study to characterize the safety and clinical activity of ATL001, autologous clonal neoantigen reactive T cells (cNeT) administered intravenously in adults with metastatic or recurrent melanoma.

Condition or disease Intervention/treatment Phase
Melanoma Biological: ATL001 Drug: Checkpoint Inhibitor Phase 1 Phase 2

Detailed Description:

This is a first-in-human, open-label, multi-centre, phase I/IIa study to characterize the safety and clinical activity autologous clonal neoantigen reactive T cells (cNeT) administered intravenously in adults with metastatic or recurrent melanoma.

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)

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 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 Metastatic or Recurrent Melanoma
Actual Study Start Date : August 15, 2019
Estimated Primary Completion Date : July 1, 2025
Estimated Study Completion Date : December 31, 2027

Resource links provided by the National Library of Medicine

MedlinePlus Genetics related topics: Melanoma
MedlinePlus related topics: Melanoma

Arms and Interventions
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Arm Intervention/treatment
Experimental: Cohort A
Following lymphodepletion, infusion of cell therapy product ATL001, followed by a low dose regimen of IL- 2.
 Biological: ATL001
ATL001 infusion
Experimental: Cohort B
Following lymphodepletion, infusion of cell therapy product ATL001 in combination with a checkpoint inhibitor, followed by a low dose regimen of IL-2.
 Biological: ATL001
ATL001 infusion

Drug: Checkpoint Inhibitor
Nivolumab
Experimental: Cohort C
Following lymphodepletion, infusion of cell therapy product ATL001, followed by a higher dose regimen of IL-2.
 Biological: ATL001
ATL001 infusion


Outcome Measures
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Primary Outcome Measures :
  1. Assessment of Treatment Emergent Adverse Events to evaluate Safety and Tolerability: CTCAE [ Time Frame: Maximum 84 month ]
    Evaluate treatment-emergent adverse events (TEAEs) and serious AEs, per CTCAE, 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 recurrent or metastatic melanoma 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).

  2. Disease Assessment for Overall Response Rate [ Time Frame: Every 6 weeks for 6 months, then every 3 months for a maximum of 84 months ]
    Evaluate the endpoint of overall 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).

  3. Disease Assessment for Time to Response and Duration of Response [ Time Frame: Every 6 weeks for 6 months, then every 3 months for a maximum of 84 months ]
    Evaluate the endpoints of time to response and duration of response (DOR) by the investigator and ICR, per RECIST v1.1 and im-RECIST.

  4. 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 investigator and ICR per RECIST v1.1 and im-RECIST.

  5. 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.

  6. 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 investigator


Eligibility Criteria
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Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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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 at the screening visit.
  2. Patient must have given written informed consent to participate in the study.
  3. Patients must have histologically confirmed diagnosis of melanoma.
  4. Patients must have received a PD-1/ PD-L1 inhibitor prior to treatment with ATL001 (unless contraindicated).
  5. Patients whose tumour is known to have a BRAF V600 mutation must have received BRAF targeted therapy (as well as a PD- 1/PD-L1 inhibitor unless contraindicated) prior to treatment with ATL001.
  6. Patient is considered medically fit enough to undergo all study procedures and interventions: procedures to procure blood and tumour tissue, including a general anaesthetic if required, and to receive fludarabine, cyclophosphamide and IL-2 at protocol doses and schedules.
  7. Patient is considered, in the opinion of the Investigator, capable of adhering to the protocol.
  8. Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1.
  9. Adequate organ function per the laboratory parameters defined in 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. 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. Anticipated life expectancy ≥ 6 months at the time of tissue procurement.
  12. Patient must have measurable disease according to RECIST v1.1

Additional Inclusion criteria will apply as per the protocol.

Exclusion Criteria:

  1. Patients with known leptomeningeal or CNS metastases at the time of screening.
  2. Patients with ocular, acral or mucosal melanoma.
  3. Patients with active infectious disease.
  4. Patients with active, known, or suspected, autoimmune disease requiring immunosuppressive treatments.
  5. Patients requiring regular treatment with steroids at a dose higher than prednisolone 10mg/day (or equivalent).
  6. Patients with a current or recent history, as determined by the Investigator, of clinically significant, progressive, and/or uncontrolled renal, hepatic, haematological, endocrine, pulmonary, cardiac, gastroenterological or neurological disease.
  7. Patients with a history of immune mediated central nervous system toxicity that was caused by, or suspected to be caused by, immunotherapy.
  8. 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.
  9. Patients who are pregnant or breastfeeding.
  10. Patients who have undergone major surgery in the previous 3 weeks.
  11. 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).
  12. Patients with a history of organ transplantation.
  13. Patients who have previously received any investigational cell or gene therapies.
  14. Patients with contraindications for cyclophosphamide, fludarabine and IL-2 at per protocol doses (see Investigator's Brochure for details).
  15. Patients with a known history of allergic reactions to amphotericin b, penicillin and/or streptomycin.

Additional Exclusion criteria will apply as per the protocol.

Contacts and Locations
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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): NCT03997474


Contacts
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Contact: Achilles Therapeutics +44 (0)20 8154 4600 info@achillestx.com

Locations
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Spain
Instituto de Investigación Sanitaria Fundación Jimenez Díaz Recruiting
Madrid, Spain, 28040
United Kingdom
Cambridge University Hospitals NHS Foundation Trust, Addenbrookes Hospital Recruiting
Cambridge, United Kingdom, CB2 0QQ
University College London Hospitals (UCLH) NHS Foundation Trust, University College Hospital Recruiting
London, United Kingdom, NW12PG
Royal Free London NHS Foundation Trust, Royal Free Hospital Recruiting
London, United Kingdom, NW3 2QG
Guys and St Thomas' NHS Foundation Trust, Guy's Hospital Recruiting
London, United Kingdom, SE19RT
The Royal Marsden NHS Foundation Trust, The Royal Marsden Hospital Recruiting
London, United Kingdom, SW3 6JJ
The Christie NHS Foundation Trust, Christie Hospital Recruiting
Manchester, United Kingdom, M20 4BX
The Newcastle Upon Tyne Hospitals NHS Foundation Trust, Freeman Hospital Recruiting
Newcastle Upon Tyne, United Kingdom, NE7 7DN
University Hospital Southampton NHS Foundation Trust, Southampton General Hospital Recruiting
Southampton, United Kingdom, SO16 6YD
Sponsors and Collaborators
Achilles Therapeutics UK Limited
Investigators
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Study Director: Medical Monitor, MD Achilles Therapeutics
More Information
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Responsible Party: Achilles Therapeutics UK Limited
ClinicalTrials.gov Identifier: NCT03997474    
Other Study ID Numbers: ATX-ME-001
First Posted: June 25, 2019    Key Record Dates
Last Update Posted: January 9, 2023
Last Verified: January 2023
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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Melanoma
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
 Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Nevi and Melanomas