Trial of Temozolomide in BAP1 Mutated Patients With Advanced or Metastatic Cutaneous Melanoma

Prior treatment

• Patients who have received a minimum of one line of chemotherapy for melanoma treatment
• Participation in or ongoing treatment with another investigational agent or use of an investigational device within 28 days prior to study treatment.
  • NB: Participants who have entered the follow-up phase if an investigational study may participate as long as it has been 4 weeks or an interval of five-half-lives, whichever the shortest is, after the last dose of the previous investigational agent.

Other illness

• Positive serology results for human immunodeficiency virus (HIV), active hepatitis B or C infection (acute or chronic) or uncontrolled infection
• Concomitant presence or history of another malignancy, except for the following: appropriately treated squamous or basal cell carcinoma of the skin (adequate healing is required prior to study entry); any other solid tumor, curatively treated and without evidence of recurrence for at least 2 years prior to study entry.
• Patient with hypersensitivity to IMP temozolomide (including hypersensitivity to dacarbazine, severe myelosuppression) or to any of its excipients.

Other

• Patients with non-cutaneous melanoma, whether uveal, mucosal, of unknown primary origin or leptomeningeal
• Subjects covered by Articles L1121-5 through L1121-8 of the Public Health Code (minors, adults under guardianship or conservatorship, patients deprived of their liberty, and pregnant or breastfeeding women).
• Any pathology that, in the investigator's opinion, may be a contraindication to the patient's participation in the clinical study, for reasons of safety or compliance with clinical study procedures.

• Adult patient (≥18 years old)
• Patients who have received information about the study and have signed an informed consent form.
• Histopathological confirmation of a diagnosis of stage III (unresectable) or stage IV (metastatic) cutaneous melanoma according to the 8th edition of the AJCC staging system.
• Patient has experienced treatment failure after undergoing at least one line of Immunotherapy with at least one immune checkpoint inhibitor (anti-PD1, anti-PD1+anti-CTLA4, or anti-PD1+anti-LAG3) and one line of targeted therapy combining BRAF and MEK inhibitors, if indicated.
• The patient must have an Eastern Cooperative Oncology Group (ECOG) performance status of 3 or lower.
• The patient must have at least one measurable lesion defined by the Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST 1.1).
• The patient must have a pathogenic BAP1 alteration identified by a molecular biology technique in tumor tissue or in circulating cell-free DNA.
• The inclusion of patients is subject to the following criteria:
• Absolute neutrophil count ≥ 1.5 x 109/L (≥ 1500 per mm3)
• Platelet count ≥ 100 x 109/L
• Hemoglobin ≥ 9 g/dL
• ASAT and/or ALAT ≤ 2.5 x Upper Limit of Normal (ULN); patient with liver metastases ≤ 5 × ULN
• Total bilirubin ≤ 1.5 x ULN
• Creatinine ≤ 1.5 x ULN or calculated creatinine clearance ≥ 50 ml/min for patients with creatinine levels \> 1.5 x ULN (according to Cockroft-Gault Appendix D) ;
• International normalized ratio (INR) or prothrombin time (PT) and activated partial thromboplastin time (aPTT) ≤ 1.5 x ULN
• Female patients with a negative highly sensitive pregnancy test, or postmenopausal female patients.