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Report for Clinical Trial NCT03878719

Developed by Shray Alag, 2020.
SNP Clinical Trial Gene

A Multicenter, Open-label Phase 1b Study of the Combination of Binimetinib and Encorafenib in Adolescent Patients With Unresectable or Metastatic BRAF V600-mutant Melanoma

This is a multicenter Phase 1b, open-label study to evaluate the pharmacokinetic, safety and efficacy of binimetinib and encorafenib co-administered to adolescent patients with BRAF V600-mutant advanced/metastatic melanoma. The study consists of a Safety Run-in Phase to determine the RDE (recommended dose in expansion), followed by an Expansion Phase.

NCT03878719 Melanoma
MeSH:Melanoma
HPO:Cutaneous melanoma Melanoma

2 Interventions

Name: binimetinib

Description: taken orally
Type: Drug
Group Labels: 2

Expansion Phase Safety Run-in Phase

Name: encorafenib

Description: taken orally
Type: Drug
Group Labels: 2

Expansion Phase Safety Run-in Phase


Primary Outcomes

Measure: Pharmacokinetic (PK) parameter (time to reach the maximum observed plasma concentration Cmax [Tmax]) for binimetinib

Time: Day 1 and Day 15 of Cycle 1, 28 day cycles

Measure: PK parameter (Cmax) for binimetinib

Time: Day 1 and Day 15 of Cycle 1, 28 day cycles

Measure: PK parameter (time of last PK sample [Tlast]) for binimetinib

Time: Day 1 and Day 15 of Cycle 1, 28 day cycles

Measure: PK parameter (area under the plasma concentration-time curve from time zero to Tlast [AUClast]) for binimetinib

Time: Day 1 and Day 15 of Cycle 1, 28 day cycles

Measure: PK parameter (Tmax) for binimetinib's active metabolite (AR00426032)

Time: Day 1 and Day 15 of Cycle 1, 28 day cycles

Measure: PK parameter (Cmax) for AR00426032

Time: Day 1 and Day 15 of Cycle 1, 28 day cycles

Measure: PK parameter (Tlast) for AR00426032

Time: Day 1 and Day 15 of Cycle 1, 28 day cycles

Measure: PK parameter (AUClast) for AR00426032

Time: Day 1 and Day 15 of Cycle 1, 28 day cycles

Measure: PK parameter (Tmax) for encorafenib

Time: Day 1 and Day 15 of Cycle 1, 28 day cycles

Measure: PK parameter (Cmax) for encorafenib

Time: Day 1 and Day 15 of Cycle 1, 28 day cycles

Measure: PK parameter (Tlast) for encorafenib

Time: Day 1 and Day 15 of Cycle 1, 28 day cycles

Measure: PK parameter (AUClast) for encorafenib

Time: Day 1 and Day 15 of Cycle 1, 28 day cycles

Measure: PK parameter (Tmax) for encorafenib's metabolite (LHY746)

Time: Day 1 and Day 15 of Cycle 1, 28 day cycles

Measure: PK parameter (Cmax) for LHY746

Time: Day 1 and Day 15 of Cycle 1, 28 day cycles

Measure: PK parameter (Tlast) for LHY746

Time: Day 1 and Day 15 of Cycle 1, 28 day cycles

Measure: PK parameter (AUClast) for LHY746

Time: Day 1 and Day 15 of Cycle 1, 28 day cycles

Measure: PK parameter (trough concentration [Ctrough]) for binimetinib

Time: at time zero Day 15 of Cycle 1, 28 day cycles

Measure: PK parameter (trough concentration [Ctrough]) for binimetinib

Time: at time zero Day 1 of Cycle 2, 28 day cycles

Measure: PK parameter (trough concentration [Ctrough]) for binimetinib

Time: at time zero Day 1 of Cycle 3, 28 day cycles

Measure: PK parameter (Ctrough) for AR00426032

Time: at time zero Day 15 of Cycle 1, 28 day cycles

Measure: PK parameter (Ctrough) for AR00426032

Time: at time zero Day 1 of Cycle 2, 28 day cycles

Measure: PK parameter (Ctrough) for AR00426032

Time: at time zero Day 1 of Cycle 3, 28 day cycles

Measure: PK parameter (Ctrough) for encorafenib

Time: at time zero Day 15 of Cycle 1, 28 day cycles

Measure: PK parameter (Ctrough) for encorafenib

Time: at time zero Day 1 of Cycle 2, 28 day cycles

Measure: PK parameter (Ctrough) for encorafenib

Time: at time zero Day 1 of Cycle 3, 28 day cycles

Measure: PK parameter (Ctrough) for LHY746

Time: at time zero Day 15 of Cycle 1, 28 day cycles

Measure: PK parameter (Ctrough) for LHY746

Time: at time zero Day 1 of Cycle 2, 28 day cycles

Measure: PK parameter (Ctrough) for LHY746

Time: at time zero Day 1 of Cycle 3, 28 day cycles

Secondary Outcomes

Measure: Incidence and severity of adverse events (AEs)

Time: From informed consent up to 30 days following last dose of study drug

Measure: Incidence of dose-limiting toxicities (DLTs)

Time: Duration of treatment for safety run-in phase, approximately 6 months, 28 day cycles

Description: Five-point Hedonic scale from 1 to 5, 5=really good

Measure: Palatability score for the pediatric formulations as assessed by an age-appropriate questionnaire for binimetinib

Time: Through Cycle 3 Day 1 in patients receiving the pediatric formulations in the Expansion Phase, 28 day cycles

Description: Five-point Hedonic scale from 1 to 5, 5=really good

Measure: Palatability score for the pediatric formulations as assessed by an age-appropriate questionnaire for encorafenib

Time: Through Cycle 3 Day 1 in patients receiving the pediatric formulations in the Expansion Phase, 28 day cycles

Measure: Objective response rate (ORR) assessed by the investigator, based on Response Criteria Evaluation in Solid Tumors (RECIST) v1.1

Time: Duration of treatment, approximately 6 months, 28 day cycles

Measure: Duration of response (DOR)

Time: Duration of treatment, approximately 6 months, 28 day cycles

Measure: Time to response

Time: Duration of treatment, approximately 6 months, 28 day cycles

Measure: Progression-free survival (PFS)

Time: Duration of treatment, approximately 6 months, 28 day cycles

Measure: One-year survival rate

Time: From first dose up to 1 year after treatment initiation

Measure: Change from Baseline in bone densitometry based on dual energy X-ray absorptiometry (DEXA) scan.

Time: Duration of treatment, approximately 6 months, 28 day cycles

Measure: Change from Baseline in calcium-phosphorus product (Ca × P)

Time: Duration of treatment, approximately 6 months, 28 day cycles

Purpose: Treatment

Allocation: Non-Randomized

Single Group Assignment


There are 2 SNPs

SNPs


1 V600E

- Histologically confirmed diagnosis of locally advanced, unresectable or metastatic cutaneous melanoma or unknown primary melanoma American Joint Committee on Cancer Stage IIIB, IIIC, or IV. - Presence of BRAF V600E or V600K mutation in tumor tissue as determined by a local or central laboratory - Adequate cardiac function: - Left ventricular ejection fraction (LVEF) ≥ 50% as determined by ECHO or multi-gated acquisition (MUGA) scan and above the institutional lower limit of normal (LLN); - Triplicate average baseline QTcF value ≤ 450 ms. - Adequate bone marrow, organ function, and laboratory parameters: - Absolute neutrophil count (ANC) ≥ 1.5 × 10⁹/L; - Hemoglobin ≥ 9 g/dL with or without transfusions; - Platelets ≥ 75 × 10⁹/L without transfusions; - Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) ≤ 2.5 × upper limit of normal (ULN); in patients with liver metastases ≤ 5 × ULN; - Total bilirubin ≤ 1.5 × ULN; - Creatinine ≤ 1.5 × institutional ULN for age, or calculated creatinine clearance ≥ 70 mL/min/1.73 --- V600E ---


2 V600K

- Histologically confirmed diagnosis of locally advanced, unresectable or metastatic cutaneous melanoma or unknown primary melanoma American Joint Committee on Cancer Stage IIIB, IIIC, or IV. - Presence of BRAF V600E or V600K mutation in tumor tissue as determined by a local or central laboratory - Adequate cardiac function: - Left ventricular ejection fraction (LVEF) ≥ 50% as determined by ECHO or multi-gated acquisition (MUGA) scan and above the institutional lower limit of normal (LLN); - Triplicate average baseline QTcF value ≤ 450 ms. - Adequate bone marrow, organ function, and laboratory parameters: - Absolute neutrophil count (ANC) ≥ 1.5 × 10⁹/L; - Hemoglobin ≥ 9 g/dL with or without transfusions; - Platelets ≥ 75 × 10⁹/L without transfusions; - Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) ≤ 2.5 × upper limit of normal (ULN); in patients with liver metastases ≤ 5 × ULN; - Total bilirubin ≤ 1.5 × ULN; - Creatinine ≤ 1.5 × institutional ULN for age, or calculated creatinine clearance ≥ 70 mL/min/1.73 --- V600E --- --- V600K ---



HPO Nodes


HPO: