ATL001 in Patients With Metastatic or Recurrent Melanoma

NCT03997474 | Terminated Phase 1 Results DMC FDA Drug

• 1 other identifier: ATX-ME-001
• Study Type: interventional
• Target: 13
• Locations: 2 countries
• Sites: 10

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.

Conditions

Melanoma

Outcome Measures

Primary Outcomes (1)

• Assessment of Treatment Emergent Adverse Events to Evaluate Safety and Tolerability: CTCAE

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

  60 months due to early termination

Secondary Outcomes (6)

• 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 Overall Response Rate

  Every 6 weeks for 6 months, then every 3 months (up to 60 months due to early study termination)

• Disease Assessment for Time to Response and Duration of Response

  Every 6 weeks for 6 months, then every 3 months for a maximum of 84 months

• Disease Assessment for Disease Control Rate

  Every 6 weeks for 6 months, then every 3 months for a maximum of 84 months

• Disease Assessment for Progression-Free Survival

  Every 6 weeks for 6 months, then every 3 months for a maximum of 84 months

Study Arms (3)

Cohort A

EXPERIMENTAL

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

Biological: ATL001

Cohort B

EXPERIMENTAL

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; Drug: Checkpoint Inhibitor

Cohort C

EXPERIMENTAL

Following lymphodepletion, 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

Checkpoint Inhibitor DRUG

Nivolumab

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 least 18 years old.
• Patient must have given written informed consent.
• Patients must have histologically confirmed diagnosis of melanoma.
• 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.
• 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.
• Anticipated life expectancy ≥ 6 months at the time of tissue procurement.

You may not qualify if:

• Patients with known leptomeningeal disease or untreated, symptomatic or progressing central nervous system (CNS) metastases. Lesions should be clinically and radiologically stable for 2 months after treatment and should not require steroids.
• Patients with ocular, acral or mucosal melanoma.
• Patients with hepatitis B or C, human immunodeficiency virus infection (HIV 1/2), syphilis or HTLV I/II infection.
• Patients requiring immunosuppressive treatments.
• Patients requiring regular steroids at a dose higher than prednisolone 10mg/day (or equivalent).
• 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 (CNS) toxicity or ≥ Grade 2 diarrhoea/colitis caused by, , previous immunotherapy within the past 6 months.
• Patients who are pregnant or breastfeeding.
• Patients who have undergone major surgery in the previous 3 weeks.
• 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.
• Patients with contraindications for protocol specified agents.

Sponsors & Collaborators

• Achilles Therapeutics UK Limited: lead

Study Sites (10)

Instituto de Investigación Sanitaria Fundación Jimenez Díaz

Madrid, 28040, Spain

Location

Centro Integral Oncologico Clara Campal (CIOCC) Hospital Universitario HM Sanchinarro

Madrid, 28050, Spain

Location

Cambridge University Hospitals NHS Foundation Trust, Addenbrookes Hospital

Cambridge, CB2 0QQ, United Kingdom

Location

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

London, NW12PG, United Kingdom

Location

Royal Free London NHS Foundation Trust, Royal Free Hospital

London, NW3 2QG, United Kingdom

Location

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

London, SE19RT, United Kingdom

Location

The Royal Marsden NHS Foundation Trust, The Royal Marsden Hospital

London, SW3 6JJ, United Kingdom

Location

The Christie NHS Foundation Trust, Christie Hospital

Manchester, M20 4BX, United Kingdom

Location

The Newcastle Upon Tyne Hospitals NHS Foundation Trust, Freeman Hospital

Newcastle upon Tyne, NE7 7DN, United Kingdom

Location

University Hospital Southampton NHS Foundation Trust, Southampton General Hospital

Southampton, SO16 6YD, United Kingdom

Location

MeSH Terms

Conditions

Melanoma

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

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 UK Limited

  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: February 4, 2019
• First Posted: June 25, 2019
• Study Start: August 15, 2019
• Primary Completion: September 3, 2024
• Study Completion: September 3, 2024
• Last Updated: March 7, 2025
• Results First Posted: March 7, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

ES (2); GB (8)