ATL001 in Patients With Metastatic or Recurrent Melanoma

• ClinicalTrials.gov Identifier: NCT03997474
• Recruitment Status: Recruiting
• First Posted: June 25, 2019
• Last Update Posted: July 29, 2021
• Sponsor: Achilles Therapeutics UK Limited
• Information provided by (Responsible Party): Achilles Therapeutics UK Limited

Study Description

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

• 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, 2023
• Estimated Study Completion Date: December 31, 2023

Arms and Interventions

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

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

• 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

Contacts

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

Locations

United Kingdom

Cambridge University Hospitals NHS Foundation Trust; Recruiting

Cambridge, United Kingdom

Contact: Brent O'Carrigan, MD

University College London Hospital (UCLH); Not yet recruiting

London, United Kingdom, NW12PG

Contact: Heather Shaw, MD

Guys and St Thomas' NHS Foundation Trust; Not yet recruiting

London, United Kingdom, SE19RT

Contact: Sophie Papa, MD

The Royal Marsden NHS Foundation Trust; Recruiting

London, United Kingdom, SW3 6JJ

Contact: Samra Turajlic, MD

The Christie NHS Foundation Trust; Recruiting

Manchester, United Kingdom, M20 4BX

Contact: Fiona Thistlethwaite, MD

Freeman Hospital; Recruiting

Newcastle Upon Tyne, United Kingdom, NE7 7DN

Contact: Prof Ruth Plummer, MD

University Hospital Southampton NHS Foundation Trust; Recruiting

Southampton, United Kingdom

Contact: Ioannis Karydis, MD

Sponsors and Collaborators

Achilles Therapeutics UK Limited

Investigators

• Study Director: Medical Monitor, MD; Achilles Therapeutics

More Information

• Responsible Party: Achilles Therapeutics UK Limited
• ClinicalTrials.gov Identifier: NCT03997474
• Other Study ID Numbers: ATX-ME-001
• First Posted: June 25, 2019
• Last Update Posted: July 29, 2021
• Last Verified: February 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

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

Additional relevant MeSH terms:

Melanoma; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas