A first-in-human clinical trial in adult patients with metastatic or recurrent melanoma of a personalised therapy targeting specific mutations that occur in all cancer cells within a single patient.

Phase 1

• Conditions: Metastatic or recurrent melanoma; MedDRA version: 20.0Level: LLTClassification code 10072454Term: Amelanotic melanomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 20.0Level: LLTClassification code 10072452Term: Angiotropic melanomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 21.1Level: LLTClassification code 10072447Term: Blue naevus-like melanomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 21.1Level: LLTClassification code 10072453Term: Blue nevus-like melanomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 20.0Level: PTClassification code 10072449Term: Desmoplastic melanomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 21.1Level: LLTClassification code 10025651Term: Malignant melanoma excisionSystem Organ Class: 100000004865; MedDRA version: 21.1Level: PTClassification code 10025650Term: Malignant melanomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 21.1Level: LLTClassification code 10025655Term: Malignant melanoma of skinSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 21.1Level: PTClassification code 10063706Term: Malignant melanoma of eyelidSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

• Registration Number: EUCTR2018-003446-16-ES
• Lead Sponsor: Achilles Therapeutics UK Limited

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2022-06-02
• Last Update Posted: 8 August 2022

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 40

Inclusion Criteria

Inclusion criteria will apply at multiple timepoints.

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 indicated by the following laboratory parameters:
a. Haemoglobin = 10.0 g/dL.
b. White Blood Cell Count (WBC) = 3.0 x10^9/L.
c. Absolute Neutrophil Count (ANC) = 1.5 x10^9/L.
d. Platelets = 100 x10^9/L.
e. INR/PT and APTT < 1.5x ULN, unless receiving therapeutic anticoagulation. Investigator discretion is required to ensure surgery is safe or that anticoagulants can be safely stopped.
f. AST or ALT = 2.5x ULN.
g. Bilirubin < 1.5x ULN (or < 3x ULN if Gilbert’s Syndrome).
h. Creatinine clearance/estimated glomerular filtration rate (GFR) = 50 mL/min.
10. Female patients who are of childbearing potential must agree to use a highly effective method of contraception during the study and 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. See Section 4.3 for details of acceptable methods of contraception.
In addition to a re-evaluation of criteria 1-10, the following inclusion criteria must also be met prior to tissue procurement:
11. To be eligible to enter this study for procurement, the patient must fall into one of the following groups (Note: Patients will not receive ATL001 until their disease has progressed or recurred following standard of care therapies, or if they cannot tolerate standard of care therapies – see inclusion number 13):
a) Patients with metastatic or recurrent disease who have had no prior systemic therapy for advanced disease and who have accessible sites of disease suitable for collection of adequate tissue for ATL001 manufacture.
b) Patients with metastatic or recurrent disease who are on or have completed first line systemic therapy and have accessible sites of disease suitable for collection of adequate tissue for ATL001 manufacture.
c) Other patients with advance stage disease for whom no other alternative approved treatments are available, may be considered on a case-by-case basis and should be discussed with the Sponsor prior to enrolment.
12. Anticipated life expectancy = 6 months at the time of tissue procurement.
In addition to a re-evaluation of criteria 1-10, the following inclusion criteria must also be met prior to lymphodepletion for treatment with ATL001:
13. Patients must have metas

Exclusion Criteria

Exclusion criteria will apply at multiple timepoints.

Exclusion Criteria:
1. Patients with known leptomeningeal disease or central nervous system (CNS) metastases that are untreated or symptomatic or progressing.
2. Patients with ocular, acral or mucosal melanoma.
3. Patients with hepatitis B or C, human immunodeficiency virus infection (HIV1/2), syphilis or HTLVI/II infection (see Section 6.1.1).
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 10 mg/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 postimmunotherapy (with uninflamed mucosa by visual assessment following discontinuation of immune suppression other than permitted modified release steroids) 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 confirmed history of allergic reactions to amphotericin b, penicillin and/or streptomycin.
In addition to 1-15, the following exclusion criteria apply to patients who have received anti-cancer therapy prior to study entry:
16. Patients who have received any cytotoxic chemotherapy within the 3 weeks prior to tissue and blood procurement.
In addition, the following exclusion criteria will apply for eligibility for Cohort B:
17. Patients with a history of (non-infectious) pneumonitis that required systemic steroids, or current pneumonitis/interstitial lung disease.
18. Patients with a history of severe hypersensitivity to a monoclonal antibody, allergy or hypersensitivity to nivolumab itself and/or its components.
19. Patients who have received a live vaccination within the 28 days prior to the first dose of nivolumab.
20. Patients with any contraindications for nivolumab (Refer to the latest available prescribing information (e.g. SmPC) for reference safety information for nivolumab).
In addition, the following exclusion criteria will apply for eligibility for Cohort C:
21. Patients with a Left Ventricular Ejection Fraction (LVEF) < 45%. Patients > 60 years of age must have had an echocardiogram within the previous 60 days of screening.
22. Patients with a forced expiratory volume in one second (FEV1) of less than o equal to 60% of their predicted normal.
All exclusion criteria, except 3 and 16, will apply again prior to lymp

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified