2024-511404-17-00招募中3 期
A RANDOMIZED, OPEN-LABEL PHASE 3 STUDY IN PATIENTS WITH PREVIOUSLY TREATED UNRESECTABLE OR METASTATIC NRAS MUTANT CUTANEOUS MELANOMA COMPARING THE COMBINATION OF NAPORAFENIB + TRAMETINIB TO PHYSICIAN’S CHOICE OF THERAPY (DACARBAZINE, TEMOZOLOMIDE OR TRAMETINIB MONOTHERAPY) WITH A DOSE OPTIMIZATION LEAD-IN [SEACRAFT-2]
Erasca Inc.74 个研究点 分布在 9 个国家目标入组 294 人开始时间: 2024年9月16日最近更新:
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 发起方
- 入组人数
- 294
- 试验地点
- 74
- 主要终点
- Stage 1 (Dose Optimization) - Analysis of the totality of the safety, pharmacokinetics (PK), and preliminary efficacy data including exposure response relationships for tolerability, safety, and efficacy from Stage 1 and throughout the naporafenib program
研究概览
简要总结
Stage 1 (Dose Optimization) - To select the optimal dose of naporafenib + trametinib to be studied in Stage 2 Stage 2 (Registration-Enabling Portion) - To compare PFS and overall survival (OS) for patients with NRASm melanoma who are randomized to receive the combination of naporafenib + trametinib to that of patients who are randomized to physician’s choice of therapy (dacarbazine, temozolomide, or trametinib monotherapy)
入排标准
- 年龄范围
- 18 years 至 65+ years（18-64 Years, 65+ Years）
- 接受健康志愿者
- 是
入选标准
- •Patient has voluntarily agreed to participate by giving written informed consent in accordance with International Council for Harmonization (ICH)/GCP guidelines and applicable local regulations
- •Age ≥ 18 years
- •Histologically or cytologically confirmed unresectable or metastatic cutaneous (includes acral) melanoma
- •Documentation of an NRAS mutation (tumor tissue or blood) prior to first dose of study drug(s) as determined locally with an analytically validated assay in a certified testing laboratory.
- •Archival tumor tissue collected within 5 years prior to enrollment must be confirmed to be available at the time of Screening, which may be submitted before or after enrollment for exploratory biomarker analysis.
- •Must have received an anti-PD-1/L1 based regimen (monotherapy or combination). Patient must have documented disease progression either while receiving therapy or within 12 weeks of last dose of the most recent anti-PD-1/L1 based regimen; the patient is eligible if they have received other therapies between the most recent anti-PD-1/L1 based regimen and enrollment.
- •ECOG performance status 0, 1 or 2
- •Presence of at least 1 measurable lesion according to RECIST v1.1
- •Able to swallow oral medication.
排除标准
- •Patients with uveal or mucosal melanoma
- •Prior therapy with an ERK-, MEK-, RAF-, or RAS-inhibitor
- •Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of study drug(s) (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, small bowel resection)
- •History or current evidence of retinal vein occlusion (RVO) or current risk factors for RVO (e.g., uncontrolled glaucoma or ocular hypertension, history of hyperviscosity or hypercoagulability syndrome)
- •Symptomatic CNS metastases that are neurologically unstable. Patients with controlled CNS metastases are eligible.
- •Patients receiving treatment with herbal medicine known to cause liver toxicity, which cannot be discontinued 7 days prior to first dose of study drug(s) and for the duration of the study.
- •Are pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the trial
结局指标
主要结局
Stage 1 (Dose Optimization) - Analysis of the totality of the safety, pharmacokinetics (PK), and preliminary efficacy data including exposure response relationships for tolerability, safety, and efficacy from Stage 1 and throughout the naporafenib program
Stage 1 (Dose Optimization) - Analysis of the totality of the safety, pharmacokinetics (PK), and preliminary efficacy data including exposure response relationships for tolerability, safety, and efficacy from Stage 1 and throughout the naporafenib program
Stage 2 (Registration-Enabling Portion) - PFS using RECIST v1.1 per blinded independent central review (BICR)
Stage 2 (Registration-Enabling Portion) - PFS using RECIST v1.1 per blinded independent central review (BICR)
Stage 2 (Registration-Enabling Portion) - OS
Stage 2 (Registration-Enabling Portion) - OS
次要结局
- Stage 1 (Dose Optimization) - Using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1: • Objective response rate (ORR) • Disease control rate (DCR) • Duration of response (DOR) • Progression-free survival (PFS) • Time to response (TTR)
- Stage 1 (Dose Optimization) - Safety: incidence and severity of adverse events (AE) and serious adverse events (SAE), changes from baseline in laboratory values, vital signs, and cardiac assessments (electrocardiogram [ECG], echocardiogram [ECHO]/multigated acquisition [MUGA]) Tolerability: AEs leading to dose interruptions, reductions, and permanent discontinuation of study drug(s)
- Stage 1 (Dose Optimization) - Plasma concentrations of naporafenib and trametinib as combination therapy and plasma concentrations of trametinib as monotherapy obtained via sparse sampling for population PK modeling
- Stage 2 (Registration-Enabling Portion) - Using RECIST v1.1, per BICR: • ORR • DOR
- Stage 2 (Registration-Enabling Portion) - Safety: Incidence and severity of AEs and SAEs, changes from baseline in laboratory values, vital signs, and cardiac assessments (ECG, ECHO/ MUGA) Tolerability: AEs leading to dose interruptions, reductions, and permanent discontinuation of study drug(s)
- Stage 2 (Registration-Enabling Portion) - Using RECIST v1.1, per investigator assessment: • PFS • ORR • DOR • DCR • TTR
- Stage 2 (Registration-Enabling Portion) - Plasma concentrations of naporafenib and trametinib as combination therapy obtained via sparse sampling for population PK modeling
- Stage 2 (Registration-Enabling Portion) - Change from baseline in: • EORTC QLQ-C30 subscales • PRO CTCAE® symptoms Change from baseline to landmark timepoint(s) for one or more of the above measures; specific endpoints of interest will be selected based on data from Stage 1 and prespecified before initiating Stage 2.
研究者
Vice President, Clinical Operations
Scientific
Erasca Inc.
研究点 (74)
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