Clinical trial NCT03997474: ATL001 in Patients With Metastatic or Recurrent Melanoma
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Melanoma
Lead sponsor: Achilles Therapeutics UK Limited
Sponsor class: INDUSTRY
First posted: 2019-06-25
Enrollment: 13
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

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.

Primary outcomes:
measure: Assessment of Treatment Emergent Adverse Events to Evaluate Safety and Tolerability: CTCAE
timeFrame: 60 months due to early termination
Secondary outcomes:
measure: Disease Assessment for Change From Baseline in Tumour Size
timeFrame: Every 6 weeks for 6 months, then every 3 months for a maximum of 84 months
measure: Disease Assessment for Overall Response Rate
timeFrame: Every 6 weeks for 6 months, then every 3 months (up to 60 months due to early study termination)
measure: Disease Assessment for Time to Response and Duration of Response
timeFrame: Every 6 weeks for 6 months, then every 3 months for a maximum of 84 months
measure: Disease Assessment for Disease Control Rate
timeFrame: Every 6 weeks for 6 months, then every 3 months for a maximum of 84 months
measure: Disease Assessment for Progression-Free Survival
timeFrame: Every 6 weeks for 6 months, then every 3 months for a maximum of 84 months
measure: Overall Survival
timeFrame: Every 6 weeks for 6 months, then every 3 months for a maximum of 84 months
Other outcomes:
Locations:
city: Madrid
country: Spain
facility: Instituto de Investigación Sanitaria Fundación Jimenez Díaz
city: Madrid
country: Spain
facility: Centro Integral Oncologico Clara Campal (CIOCC) Hospital Universitario HM Sanchinarro
city: Cambridge
country: United Kingdom
facility: Cambridge University Hospitals NHS Foundation Trust, Addenbrookes Hospital
city: London
country: United Kingdom
facility: University College London Hospitals (UCLH) NHS Foundation Trust, University College Hospital
city: London
country: United Kingdom
facility: Royal Free London NHS Foundation Trust, Royal Free Hospital
city: London
country: United Kingdom
facility: Guys and St Thomas' NHS Foundation Trust, Guy's Hospital
city: London
country: United Kingdom
facility: The Royal Marsden NHS Foundation Trust, The Royal Marsden Hospital
city: Manchester
country: United Kingdom
facility: The Christie NHS Foundation Trust, Christie Hospital
city: Newcastle Upon Tyne
country: United Kingdom
facility: The Newcastle Upon Tyne Hospitals NHS Foundation Trust, Freeman Hospital
city: Southampton
country: United Kingdom
facility: University Hospital Southampton NHS Foundation Trust, Southampton General Hospital
Study officials:
affiliation: Achilles Therapeutics UK Limited
name: Medical Monitor, MD
role: STUDY_DIRECTOR
References: