A Multicenter, Randomized, Open-label, 2-arm, Phase II Study With a Safety lead-in Phase Evaluating the Combination of Encorafenib and Cetuximab Versus Irinotecan/Cetuximab or Infusional 5-fluorouracil (5-FU)/Folinic Acid (FA)/Irinotecan (FOLFIRI)/Cetuximab in Chinese Patients With BRAF V600E Mutant Metastatic Colorectal Cancer.

简要总结

主要结局

次要结局

• Safety Lead-in Phase: Type and severity of Adverse Events (AEs) and Serious Adverse Events (SAEs) according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.03(Informed consent through to study completion, approximately from 18 to 35 months)
• Safety Lead-in Phase: Incidence of treatment-emergent adverse events (TEAEs) related to notable or abnormal changes from baseline of physical examinations(Day 1 through to study completion, approximately from 18 to 35 months)
• Safety Lead-in Phase: Incidence of dose interruptions, dose modifications and discontinuations due to adverse events (AEs)(Day 1 until end of treatment, approximately 1 year)
• Safety Lead-in Phase: Incidence of treatment-emergent adverse events (TEAEs) related to notable or abnormal changes in vital signs from baseline of vital sign examinations.(Day 1 through to study completion, approximately from 18 to 35 months)
• Safety Lead-in Phase: Incidence of treatment-emergent adverse events (TEAEs) related to notable or abnormal changes from baseline of 12-lead electrocardiograms (ECGs)(Day 1 through to study completion, approximately from 18 to 35 months)
• Safety Lead-in Phase: Incidence of treatment-emergent adverse events (TEAEs) related to notable changes in clinical safety laboratory parameters from baseline.(Day 1 through to study completion, approximately from 18 to 35 months)
• Safety Lead-in Phase: Pharmacokinetic (PK) parameter derived from serum concentration of cetuximab maximum concentration (Cmax) in Chinese participants(Day 1 of Cycles 1 and 2; Each cycle = 28 days)
• Randomized Phase 2: Overall Response Rate (ORR)(Day 1 through to study completion, approximately from 12 to 29 months)
• Safety Lead-in Phase: Incidence of development of of keratoacanthoma and/or squamous cell carcinoma and new primary melanoma by dermatological examinations(Screening (Day -28 to -1) through to study completion, approximately from 18 to 35 months)
• Safety Lead-in Phase: Performance status assessment using the Eastern Co-operative Oncology Group (ECOG) performance status scale(Screening (Day -28 to -1) through to study completion, approximately from 18 to 35 months)
• Safety Lead-in Phase: Plasma concentrations of encorafenib(Day 1 of Cycles 1 and 2; Each cycle = 28 days)
• Safety Lead-in Phase: Pharmacokinetic (PK) parameter derived from serum concentration of cetuximab area under curve (AUC) in Chinese participants(Day 1 of Cycles 1 and 2; Each cycle = 28 days)
• Safety Lead-in Phase: Pharmacokinetic (PK) parameter derived from plasma concentration of encorafenib minimum concentration (Cmin) in Chinese participants(Day 1 of Cycles 1 and 2; Each cycle = 28 days)
• Safety Lead-in Phase: Pharmacokinetic (PK) parameter derived from serum concentration of cetuximab minimum concentration (Cmin) in Chinese participants(Day 1 of Cycles 1 and 2; Each cycle = 28 days)
• Safety Lead-in Phase: Pharmacokinetic (PK) parameter derived from plasma concentration of encorafenib maximum concentration (Cmax) in Chinese participants(Day 1 of Cycles 1 and 2; Each cycle = 28 days)
• Safety Lead-in Phase: Serum concentrations of cetuximab(Day 1 of Cycles 1 and 2; Each cycle = 28 days)
• Safety Lead-in Phase; Pharmacokinetic (PK) parameter derived from plasma concentration of encorafenib area under curve (AUC) in Chinese participants(Day 1 of Cycles 1 and 2; Each cycle = 28 days)
• Safety Lead-in Phase: Objective response rate (ORR)(Day 1 through to study completion, approximately from 18 to 35 months)
• Safety Lead-in Phase: Duration of Response (DOR) (months); defined for responders complete response (CR) or partial response (PR) only, is duration of time from the date of the first documented response to the earliest date of disease progression(Day 1 through to study completion, approximately from 18 to 35 months)
• Randomized Phase 2: Progression-free survival (PFS)(Day 1 through to study completion, approximately from 12 to 29 months)
• Randomized Phase 2: Duration of Response (DOR)(Day 1 through to study completion, approximately from 12 to 29 months)
• Randomized Phase 2: Disease control rate (DCR)(Day 1 through to study completion, approximately from 12 to 29 months)
• Randomized Phase 2: Time to Response (TTR)(Day 1 through to study completion, approximately from 12 to 29 months)
• Randomized Phase 2: Overall Survival (OS)(Day 1 through to study completion, approximately from 12 to 29 months)
• Randomized Phase 2: Type and severity of adverse events (AEs) and serious adverse events (SAEs) according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.03(Informed consent date through to study completion, approximately from 12 to 29 months)
• Randomized Phase 2: Incidence of treatment-emergent adverse events (TEAEs) related to notable or abnormal changes from baseline of physical examinations(Day 1 through to study completion, approximately from 12 to 29 months)
• Randomized Phase 2: To determine if there is any change from baseline in the Functional Assessment of Cancer Therapy-Colon Cancer (FACT-C) questionnaire scores(Day 1 through to study completion, approximately from 12 to 29 months)
• Randomized Phase 2: Incidence of treatment-emergent adverse events (TEAEs) related to notable changes in vital signs from baseline.(Day 1 through to study completion, approximately from 12 to 29 months)
• Incidence of treatment-emergent adverse events (TEAEs) related to notable or abnormal changes to electrocardiogram evaluations from baseline(Day 1 through to study completion, approximately from 12 to 29 months)
• Randomized Phase 2: Incidence of treatment-emergent adverse events (TEAEs) related to notable changes in clinical safety laboratory parameters from baseline.(Day 1 through to study completion, approximately from 12 to 29 months)
• Randomized Phase 2: Incidence of development of keratoacanthoma and/or squamous cell carcinoma and new primary melanoma by dermatological examinations(Day 1 through to study completion, approximately from 12 to 29 months)
• Randomized Phase 2: To determine the performance status using the Eastern Co-operative Oncology Group (ECOG) performance status scale.(Day 1 through to study completion, approximately from 12 to 29 months)
• Randomized Phase 2: To determine if there is any change from baseline in the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire for Cancer Patients (EORTC QLQ-C30) questionnaire scores(Day 1 through to study completion, approximately from 12 to 29 months)
• Randomized Phase 2: To determine if there is any change from baseline in the European Quality of Life-5 Dimensions-5 Levels (EQ-5D-5L) questionnaire scores.(Day 1 through to study completion, approximately from 12 to 29 months)
• Randomized Phase 2: To determine if there is any changes in the Patient Global Impression of Change (PGIC) questionnaire scores.(Day 1 through to study completion, approximately from 12 to 29 months)
• Randomized Phase 2: Plasma concentrations of encorafenib(Day 1 of Cycles 1 and 2; Each cycle = 28 days)
• Randomized Phase 2: Serum concentrations of cetuximab(Day 1 of Cycles 1 and 2; Each cycle = 28 days)
• Randomized Phase 2; Pharmacokinetic (PK) parameter derived from plasma concentration of encorafenib area under curve (AUC) in Chinese participants(Day 1 of Cycles 1 and 2; Each cycle = 28 days)
• Randomized Phase 2: Pharmacokinetic (PK) parameter derived from serum concentration of cetuximab area under curve (AUC) in Chinese participants(Day 1 of Cycles 1 and 2; Each cycle = 28 days)
• Randomized Phase 2: Pharmacokinetic (PK) parameter derived from plasma concentration of encorafenib minimum concentration (Cmin) in Chinese participants(Day 1 of Cycles 1 and 2; Each cycle = 28 days)
• Randomized Phase 2: Pharmacokinetic (PK) parameter derived from serum concentration of cetuximab minimum concentration (Cmin) in Chinese participants(Day 1 of Cycles 1 and 2; Each cycle = 28 days)
• Randomized Phase 2: Pharmacokinetic (PK) parameter derived from plasma concentration of encorafenib maximum concentration (Cmax) in Chinese participants(Day 1 of Cycles 1 and 2; Each cycle = 28 days)
• Randomized Phase 2: Pharmacokinetic (PK) parameter derived from serum concentration of cetuximab maximum concentration (Cmax) in Chinese participants(Day 1 of Cycles 1 and 2; Each cycle = 28 days)
• Randomized Phase 2: Population pharmacokinetic (PK) analysis using the ARRAY 818 302 study PK data(Day 1 through to study completion, approximately from 12 to 29 months)