Randomised, Multicentre, Multinational, Double-Blind Integrated Study to Compare the Pharmacokinetics, Efficacy, Safety, and Immunogenicity of MB11 (Proposed Nivolumab Biosimilar) Versus EU-/US-Opdivo in Subjects With Previously Untreated Advanced (Unresectable or Metastatic) Melanoma (LEON Study)

Condition studied

Previously Untreated Advanced (Unresectable or Metastatic) Melanoma

Investigational medicinal product(s)

Eligibility

Primary endpoint

Co-Primary Endpoints: - PK: • AUC0-336 between Cycle 1 and Cycle 2 (for Estimand 1a) • AUCss, between Cycle 8 and Cycle 9 (for Estimand 1b) - Efficacy, assessed by a BICR per RECIST v1.1:, • bOR where a responder must have achieved CR or PR while alive, prior to permanent treatment discontinuation, prior to use of other anti-cancer therapies and by 24 weeks after Day 1 (for the FDA Primary Estimand 2a and EMA Primary Estimand 2b), Supportive efficacy endpoint (assessed by BICR per RECIST v 1.1): • Composite bOR where responder must be alive, able to remain on or resume treatment, and achieved CR or PR without use of other anti-cancer therapies up to 24 weeks after Day 1 (for Estimand 2c)

Endpoint detail

Secondary efficacy endpoints assessed by BICR at the following time points post Day 1: • Composite OR at 10, 16, 24, 32, and 52 weeks • PFS at 24 and 52 weeks • DOR • OS at 24 and 52 weeks PK endpoints, not covered by the primary endpoints: • Cmax in Cycle 1 and Cycle 8 • Ctrough: Cycle 1 to EOT visit as per the SoE, Safety endpoints include (52 weeks from baseline [Day 1] and up to EOS) • Incidence, nature and severity of TEAE, including SAEs, SUSARs and AESIs over the study period. • Other safety endpoints as follows: o Absolute values and changes from baseline in: o Clinical laboratory assessments (haematology, clinical chemistry [including selected hormone panel], coagulation and urinalysis)., o Vitals signs parameters (systolic and diastolic blood pressure, pulse rate, respiratory rate, and body temperature). o Incidence of abnormalities in: o Clinical laboratory parameters o 12-lead ECG o Physical examination, Immunogenicity endpoints over the study include (time frame: 52 weeks from baseline [Day 1] as per SoE): • ADAs • NAbs in ADA (+) samples • Titres in ADA (+) samples