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

Recruiting

• Conditions: Metastatic or recurrent melanoma; MedDRA version: 21.1Level: LLTClassification code: 10025656Term: Malignant melanoma of skin of ear and external auditory canal Class: 10029104; MedDRA version: 20.0Level: PTClassification code: 10079054Term: Naevoid melanoma Class: 100000004864; MedDRA version: 20.0Level: LLTClassification code: 10027155Term: Melanoma skin Class: 10029104; Therapeutic area: Diseases [C] - Neoplasms [C04]; MedDRA version: 21.1Level: PTClassification code: 10029488Term: Nodular melanoma Class: 100000004864; MedDRA version: 21.1Level: LLTClassification code: 10025658Term: Malignant melanoma of skin of eyelid including canthus Class: 10029104; MedDRA version: 20.0Level: LLTClassification code: 10027481Term: Metastatic melanoma Class: 10029104; MedDRA version: 21.1Level: LLTClassification code: 10056792Term: Malignant melanoma of skin of trunk excl scrotum Class: 10029104; MedDRA version: 20.0Level: PTClassification code: 10066600Term: Melanoma recurrent Class: 100000004864

• Registration Number: CTIS2024-513062-19-00
• Lead Sponsor: Achilles Therapeutics UK Limited

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2024-04-26
• Last Update Posted: 22 July 2024

Recruitment & Eligibility

• Status: Recruiting
• Sex: All
• Target Recruitment: 40

Inclusion Criteria

Patient must be at least 18 years old at the screening visit, 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, To be eligible to enter this study for procurement, the patient must fall into one of the following groups: 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 advanced 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, Anticipated life expectancy = 6 months at the time of tissue procurement, Patients must have metastatic melanoma and: a. Whose disease has progressed or recurred following standard of care. This includes patients who have received a component of standard of care therapy as part of a previous clinical trial in first line treatment; or b. Who are ineligible for, or who cannot tolerate, standard of care therapies. Patients who stop treatment due to immunotherapy toxicities do not need to progress in order to receive treatment with ATL001., Patients must have measurable disease according to RECIST v1.1 criteria prior to lymphodepletion, Patient is considered, in the opinion of the Investigator, well enough (i.e. ECOG Performance Status 0-1) to receive ATL001 treatment (this will be checked prior to lymphodepletion and again prior to receiving ATL001), Prior to treatment with ATL001, the treatment regimen must have included a PD-1/PD-L1 inhibitor and patients should have experienced: a. Radiological disease progression; or b. Stable disease following at least 4 doses of a PD-1/PD-L1 inhibitor, In addition to the need for highly effective contraception as outlined in Inclusion Criterion 10 above, female patients in Cohort B of childbearing potential must agree to use effective contraception during treatment with nivolumab and for at least 5 months after the last dose of nivolumab. Patients must also agree to provide a serum or urine pregnancy test before each nivolumab administration during the treatment period in Cohort B, Patient must have given written informed consent to participate in the study, Patients must have histologically confirmed diagnosis of melanoma, Patients must have received a PD-1/PD-L1 inhibitor prior to treatment with ATL001 (unless contraindicated), 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, 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

Exclusion Criteria

Patients with known leptomeningeal disease or central nervous system (CNS) metastases that are untreated or symptomatic or progressing. Lesions should be clinically and radiologically stable for 2 months after treatment, as determined by MRI or CT evaluation, in line with accepted standard of care procedures, and should not require steroids, 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 cyclophosphamide, fludarabine and IL-2 at per protocol doses, Patients with a confirmed history of allergic reactions to amphotericin b, penicillin and/or streptomycin, Patients who have received any cytotoxic chemotherapy within the 3 weeks prior to tissue and blood procurement, Patients with a history of (non-infectious) pneumonitis that required systemic steroids, or current pneumonitis/interstitial lung disease, Patients with a history of severe hypersensitivity to a monoclonal antibody, allergy or hypersensitivity to nivolumab itself and/or its components, Patients who have received a live vaccination within the 28 days prior to the first dose of nivolumab, Patients with ocular, acral or mucosal melanoma, Patients with any contraindications for nivolumab, Patients with a Left Ventricular Ejection Fraction (LVEF) < 45%, Patients with a forced expiratory volume in one second (FEV1) of less than or equal to 60% of their predicted normal, Patients who have received a live vaccination within the 28 days prior to lymphodepletion, Patients with an active infection requiring antibiotics, Patients who have received any cytotoxic chemotherapy within the 3 weeks prior to lymphodepletion, Patients with hepatitis B or C, human immunodeficiency virus infection (HIV1/2), syphilis or HTLVI/II infection, Patients with active, known, or suspected, autoimmune disease requiring immunosuppressive treatments, Patients requiring regular treatment with steroids at a dose higher than prednisolone 10 mg/day (or equivalent), 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, Patients with a history of immune mediated central nervous system toxicity that was caused by, or suspected to be caused by, immunotherapy, 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 following discontinuation of immune suppression other than permitted modified release steroids) are not excluded, Patients who are pregnant or breastfeeding

Study & Design

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

Primary Outcome Measures

Name	Time	Method
Main Objective: To assess the safety and tolerability of ATL001 as a monotherapy and in combination with nivolumab;Secondary Objective: To evaluate the clinical activity of ATL001 treatment as a monotherapy and in combination with nivolumab;Primary end point(s): Frequency and severity of adverse events (AEs) and serious adverse events (SAEs) following tissue procurement and administration of lymphodepletion agents, ATL001 (monotherapy or in combination with nivolumab) and IL-2

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s):Overall survival (OS);Secondary end point(s):Percentage change from baseline in tumour size at 6 weeks, 12 weeks and best change from baseline;Secondary end point(s):Overall Response Rate (ORR) (based on RECIST v1.1 and imRECIST);Secondary end point(s):Time to response (based on RECIST v1.1 and imRECIST);Secondary end point(s):Duration of response (based on RECIST v1.1 and imRECIST);Secondary end point(s):Disease Control Rate (CR + PR + durable SD) (based on RECIST v1.1);Secondary end point(s):Progression free survival (PFS) (based on RECIST v1.1 and imRECIST)