Multicentre, single-arm, open-label efficacy, pharmacokinetics, and safety study to demonstrate non-inferiority of prolgolimab 250 mg every 3 weeks versus historical data for prolgolimab 1 mg/kg every 2 weeks in patients with unresectable or metastatic melanoma, as well as collecting pharmacokinetics and safety data.

The study is conducted under the same conditions as the previously conducted study BCD-100-2/MIRACULUM. This means that this Study No. BCD-100-8/FLAT has identical parameters such as:

• selection criteria for subjects in the study, defining the population,
• research centers,
• procedures for evaluating effectiveness and safety,
• permitted prior and concomitant therapy of the underlying disease.

Inclusion Criteria:

• Signed informed consent and the subject's ability to comply with the protocol requirements.
• Age ≥18 years at the time of informed consent.
• Histologically confirmed unresectable or metastatic melanoma (with available documented evidence of relevant examinations).
• Primarily detected advanced or metastatic melanoma, or the disease progression on or after previous systemic therapy.
• Measurable target tumor lesions (at least 1 lesion) according to RECIST 1.1 criteria, confirmed by an independent reviewer.
• ECOG score 0-1.
• Absence of severe organ and system disorders.
• Life expectancy of at least 12 weeks at screening.
• For patients of childbearing potential: willingness to use reliable methods of contraception throughout the study, from the time of informed consent and for up to 6 weeks after the last dose of the study drug.
• Available blocks for a histological examination and/or the patient's consent for collection of biopsy43 samples to obtain histological material to assess the PD-L1 status.

Exclusion Criteria:

• Patients with severe concomitant disorders, life-threatening acute complications of the primary disease (including massive pleural, pericardial, or peritoneal effusions requiring intervention, pulmonary lymphangitis) at the time of informed consent.
• CNS metastases that are progressing or associated with clinical symptoms (e.g., cerebral edema, spinal compression) or requiring the use of glucocorticosteroids and/or anticonvulsants;
• Ongoing concomitant diseases at the time of screening increasing the risk of severe adverse events during the study treatment.
• The need for glucocorticoids or any other drugs with immunosuppressive effects.
• Hematologic abnormalities.
• Renal impairment.
• Hepatic impairment.
• Increased LDH >2 ULN.
• Prior treatment with anti-CTLA4 and/or anti-PD-1/PD-L1/PDL-2 drugs.
• Prior targeted therapy.
• A history of malignancies, except for radically treated diseases in remission for over 5 years prior to starting the study.
• Conditions limiting the patient's ability to comply with the protocol requirements (dementia, neurologic or mental disorders, drug or alcohol addiction, etc).
• Simultaneous participation in other clinical studies55 or participation in other clinical studies within 30 days prior to starting the study treatmen.
• Acute infections or activation of chronic infectious diseases within 28 days prior to the beginning of the study treatment.
• Active hepatitis B, active hepatitis C, HIV-infection, syphilis.
• Impossibility to administer the study drug intravenously.
• Impossibility to perform imaging examinations requiring administration of intravenous contrast media.
• Hypersensitivity to any of the components of BCD-100.
• A history of hypersensitivity to monoclonal antibody products.
• Pregnancy or breastfeeding.