Metastatic or recurrent melanoma MedDRA version: 21.1 Level: PT Classification code 10025650 Term: Malignant melanoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 21.1 Level: LLT Classification code 10025651 Term: Malignant melanoma excision System Organ Class: 100000004865 MedDRA version: 21.1 Level: PT Classification code 10025652 Term: Malignant melanoma in situ System Organ Class: 10029104 - Neoplasms benign, malignant
Conditions
Sponsors
Achilles Therapeutics Limited
Eligibility
Sex/Gender
All
Inclusion criteria
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 inhibitor prior to treatment with ATL001. 5. Patients whose tumour is known to have a BRAF V600 mutation must have received BRAF targeted therapy (as well as a PD-1 inhibitor) 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. PT and APTT < 1.5x ULN (unless receiving therapeutic anticoagulation). 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. Patients with female partners of childbearing potential must agree to use adequate contraception for at least 6 months after the ATL001 infusion. See Section 4.3 for details of acceptable methods of contraception. In addition to 1-10, the following inclusion criteria must 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: 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 1-10, the following inclusion criteria must be met prior to lymphodepletion for treatment with ATL001: 13. Patients must have metastatic melanoma whose disease has progressed or recurred following standard of care or who are ineligible for, or who cannot tolerate, standard of care therapies, e.g. immune checkpoint inhibitors. 14. Patients must have measurable disease according to RECIST v1.1 criteria prior to lymphodepletion. (If patients have no measurable disease following standard therapy, lymphodepletion and ATL001 treatment may be delayed until there is evidence of measurable disease). 15. Patient is considered well enough to receive ATL001 treatment (this will be checked prior to lymphodepleti
Exclusion criteria
Exclusion criteria: Exclusion criteria will apply at multiple timepoints. Exclusion Criteria: 1. Patients with known leptomeningeal disease or CNS metastases at the time of screening. 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 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 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 cyclophosphamide, fludarabine and IL-2 at per protocol doses (see Investigator’s Brochure for details). 14. Patients with a known history of allergic reactions to amphotericin b, penicillin and/or streptomycin. In addition to 1-14, the following exclusion criteria apply to patients who have received anti-cancer therapy prior to study entry: 15. Patients who have received any cytotoxic chemotherapy within the 3 weeks prior to blood and tumour tissue procurement. In addition, the following exclusion criteria will apply for eligibility for Cohort B: 16. Patients with any contraindications for nivolumab (Refer to the latest available prescribing information (e.g. SmPC) or the Investigator's Brochure for safety information for nivolumab). In addition to 1-14, the following exclusion criteria apply to all patients prior to lymphodepletion for treatment with ATL001: 17. Patients who have received a live vaccination within the 28 days prior to lymphodepletion. 18. Patients with an active infection requiring antibiotics. 19. Patients who have received any cytotoxic chemotherapy within the 3 weeks prior to lymphodepletion.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the safety and tolerability of the investigational product after administration to patients.;Secondary Objective: To evaluate if patients have a clinically meaningful response to the investigational product.;Primary end point(s): The primary outcome measure is the frequency and severity of adverse events and serious adverse events following tissue procurement and administration of lymphodepletion agents, ATL001 and IL-2.;Timepoint(s) of evaluation of this end point: The following interim analyses of efficacy will be conducted: 1. When approximately 10 evaluable patients have been followed up for 6 and 12 weeks. 2. When all patients in a treatment cohort separately have been followed up for 12 weeks. 3. A final analysis when all patients have either died or have been followed up for 2 years. Additional reviews of data may be undertaken as it arises and as deemed necessary by the Sponsor. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): To evaluate the clinical efficacy of ATL001 treatment. • Percentage change from baseline in tumour size at 6 weeks, 12 weeks and best change from baseline • Best percentage change from baseline in tumour size • Overall Response Rate (ORR) (based on RECIST v1.1 and imRECIST) • Time to response (based on RECIST v1.1 and imRECIST) • Duration of response (based on RECIST v1.1 and imRECIST) • Disease Control Rate (CR + PR + durable SD) (based on RECIST v1.1) • Progression free survival (PFS) (based on RECIST v1.1 and imRECIST) • Overall survival (OS);Timepoint(s) of evaluation of this end point: The following interim analyses of efficacy may be performed: 1. When approximately 10 evaluable patients have been followed up for 6 and 12 weeks. 2. When all patients in a treatment cohort separately have been followed up for 12 weeks. 3. A final analysis when all patients have either died or have been followed up for 2 years. Additional reviews of data may be undertaken as it arises and as deemed necessary by the Sponsor. | — |
Countries
United Kingdom
Contacts
Public ContactRegulatory Affairs
Achilles Therapeutics Limited
Outcome results
None listed