ATL001 in Patients With Metastatic or Recurrent Melanoma

Phase 1

Terminated

• Conditions: Melanoma
• Interventions: Biological: ATL001; Drug: Checkpoint Inhibitor

• Registration Number: NCT03997474
• Lead Sponsor: Achilles Therapeutics UK Limited

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.

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 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 Timeline

• Study First Submitted: 2019-02-04
• Study First Submitted QC: 2019-06-24
• Study First Posted: 2019-06-25
• Study Start: 2019-08-15
• Status Verified: 2024-01
• Primary Completion: 2024-09-03
• Study Completion: 2024-09-03
• Last Update Submitted: 2024-10-31
• Last Update Posted: 2024-11-01

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 13

Inclusion Criteria

1. Patient must be at least 18 years old.
2. Patient must have given written informed consent.
3. Patients must have histologically confirmed diagnosis of melanoma.
4. Patient is considered medically fit to undergo procurement of starting material and ATL001 administration procedures.
5. ECOG Performance Status 0-1.
6. Adequate organ function per the laboratory parameters defined in the protocol.
7. 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.
8. Anticipated life expectancy ≥ 6 months at the time of tissue procurement.
9. Measurable disease according to RECIST v1.1 criteria. Additional inclusion criteria will apply as per the study protocol.

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Exclusion Criteria

1. 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.
2. Patients with ocular, acral or mucosal melanoma.
3. Patients with hepatitis B or C, human immunodeficiency virus infection (HIV 1/2), syphilis or HTLV I/II infection.
4. Patients requiring immunosuppressive treatments.
5. Patients requiring regular steroids at a dose higher than prednisolone 10mg/day (or equivalent).
6. Patients with clinically significant, progressive, and/or uncontrolled renal, hepatic, haematological, endocrine, pulmonary, cardiac, gastroenterological, or neurological disease.
7. Patients with a history of immune mediated (CNS) toxicity or ≥ Grade 2 diarrhoea/colitis caused by, , previous immunotherapy within the past 6 months.
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, early prostate cancer with normal Prostate-Specific Antigen (PSA) or non-melanomatous skin cancers).
11. Patients with a history of organ transplantation.
12. Patients who have previously received any investigational cell or gene therapies.
13. Patients with contraindications for protocol specified agents.

Additional Exclusion criteria will apply as per the study protocol.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Cohort B	Checkpoint Inhibitor	Following lymphodepletion, infusion of cell therapy product ATL001 in combination with a checkpoint inhibitor, followed by a low dose regimen of IL-2.
Cohort C	ATL001	Following lymphodepletion, infusion of cell therapy product ATL001, followed by a higher dose regimen of IL-2.
Cohort A	ATL001	Following lymphodepletion, infusion of cell therapy product ATL001, followed by a low dose regimen of IL- 2.
Cohort B	ATL001	Following lymphodepletion, infusion of cell therapy product ATL001 in combination with a checkpoint inhibitor, followed by a low dose regimen of IL-2.

Primary Outcome Measures

Name	Time	Method
Assessment of Treatment Emergent Adverse Events to evaluate Safety and Tolerability: CTCAE	Maximum 84 month	Evaluate treatment-emergent adverse events (TEAEs) and serious AEs, per CTCAE, by incidence, severity and relationship to ATL001

Secondary Outcome Measures

Name	Time	Method
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	Evaluate the endpoints of time to response and duration of response (DOR) by the investigator and ICR, per RECIST v1.1 and im-RECIST.
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	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).
Disease Assessment for Overall Response Rate	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).
Disease Assessment for Disease Control Rate	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.
Disease Assessment for Progression-Free Survival	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	Every 6 weeks for 6 months, then every 3 months for a maximum of 84 months	Evaluate overall survival (OS) by investigator

Trial Locations

Locations (10)

Instituto de Investigación Sanitaria Fundación Jimenez Díaz; 🇪🇸 Madrid, Spain

Centro Integral Oncologico Clara Campal (CIOCC) Hospital Universitario HM Sanchinarro; 🇪🇸 Madrid, Spain

Cambridge University Hospitals NHS Foundation Trust, Addenbrookes Hospital; 🇬🇧 Cambridge, United Kingdom

University College London Hospitals (UCLH) NHS Foundation Trust, University College Hospital; 🇬🇧 London, United Kingdom

Royal Free London NHS Foundation Trust, Royal Free Hospital; 🇬🇧 London, United Kingdom

Guys and St Thomas' NHS Foundation Trust, Guy's Hospital; 🇬🇧 London, United Kingdom

The Royal Marsden NHS Foundation Trust, The Royal Marsden Hospital; 🇬🇧 London, 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 Kingdom