NCT05195632进行中（未招募）2 期
Multicenter, Open-label, Phase II Study With a Safety Lead-in Part Investigating the Efficacy, Safety and Pharmacokinetics of Encorafenib and Binimetinib Combination in BRAF V600E Mutated Chinese Patients With Metastatic Non-Small Cell Lung Cancer Who Are BRAF- and MEK Inhibitor Treatment-naïve
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 63
- 试验地点
- 59
- 主要终点
- Safety Lead-In (SLI) Part: Incidence of Dose-limiting toxicities (DLTs)
研究概览
简要总结
This is a phase 2, multicenter, single-arm study with a safety lead-in to investigate the efficacy, safety and pharmacokinetics of encorafenib 450 mg once daily (QD) in combination with binimetinib 45 mg twice daily (BID) (Combo450) in adult Chinese participants with metastatic unresectable stage IV BRAF V600E mutant NSCLC, who are BRAF- and MEK-inhibitor treatment-naïve and are either previously untreated or have had one line of prior therapy in metastatic setting.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •If a participant has a BRAF V600E mutational status confirmed as per local assessment, the participant might enter the main screening directly.
- •All the following inclusion criteria must be met for a participant to be eligible to be included in this study:
- •Provide a signed and dated screening Informed Consent Form (ICF).
- •Chinese male or female with age ≥ 18 years old for China mainland and ≥ 20 years old for Taiwan at the time of the screening informed consent.
- •Documented histology- and/or cytology-confirmed metastatic unresectable Non-small cell lung cancer (NSCLC (i.e. Adenocarcinoma (ADC), large cell carcinoma, squamous cell carcinoma (SCC)).
- •Presence of B-Raf Proto-Oncogene, Serine/Threonine Kinase (BRAF) V600E mutation in tumor tissue previously determined by a local assay at any time prior to screening or by the central laboratory.
- •Able to provide a sufficient amount of representative tumor specimen (primary or metastatic, archived or newly obtained) for central prospective laboratory testing of BRAF mutation status and comparison of central BRAF V600E testing in the clinical study to BRAF V600E testing with a candidate companion diagnostic.
- •BRAF- and Mitogen-activated protein kinase kinase (MEK)-inhibitor treatment-naïve participants and previously untreated or have had one line of prior therapy in metastatic setting.
- •At least one measurable disease as per investigator assessment, as defined by RECIST v1.1, which has neither been irradiated nor biopsied during the screening period.
- •Life expectancy ≥ 3 months.
- •Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or
- •Adequate hematologic function at screening and baseline.
- •Adequate hepatic function at screening and baseline.
- •Adequate renal function at screening and baseline.
- •Able to comply with the study protocol as per investigator assessment including oral drug intake, complying scheduled visits, treatment plan, laboratory tests and other study procedures.
- •Women are either postmenopausal for at least 1 year, are surgically sterile for at least 6 weeks, or child-bearing potential women must agree to take appropriate precautions to avoid pregnancy.
- •Men must agree not to father child until 90 days after the last dose of the study treatment.
排除标准
- •Participants meeting any of the following criteria are not eligible to be included in this study:
- •Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to the study drugs (encorafenib and binimetinib), or their excipients.
- •Documented Anaplastic lymphoma kinase (ALK) fusion oncogene, Reactive oxygen species (ROS) rearrangement or Epidermal growth factor receptor (EGFR) sensitizing or driver mutation.
- •Participants who have received more than one prior line of systemic therapy.
- •Receipt of anti-cancer medications or investigational drugs within the specified intervals before the first administration of study treatment.
- •Symptomatic brain metastases or other active Central nervous system (CNS) metastases.
- •Leptomeningeal disease.
- •Participant has not recovered to ≤ Grade 1 from toxic effects of prior therapy and/or complications from prior surgical intervention before starting study treatment.
- •Current use of prohibited medication ≤ 1 week prior to start of the study treatment and/or concomitantly.
- •Impairment of gastrointestinal function or disease which may significantly alter the absorption of oral study treatment.
- •Impaired cardiovascular function or clinically significant cardiovascular diseases
- •History of thromboembolic or cerebrovascular events within 3 months prior to starting the study treatments
- •History or evidence of retinal pathology considered as risk factor for Retinal vein occlusion (RVO) or neovascular macular degeneration.
- •Concurrent neuromuscular disorder associated with the potential of elevated Creatine phosphokinase (CPK)
- •Participants with active Hepatitis B Virus (HBV) or Hepatitis C Virus (HCV) or any other severe viral active infection (e.g. SARS-CoV-2 infection)
- •Evidence of active, non-infectious pneumonitis, history of interstitial lung disease that required oral or intravenous glucocorticosteroids for management.
- •Known history of a positive test for Human immunodeficiency virus (HIV) or known Acquired Immunodeficiency Syndrome (AIDS). Testing for HIV must be performed at sites where mandated locally.
- •Participants who have had major surgery (e.g. inpatient procedure with regional or general anesthesia) within 6 weeks prior to start of study treatment.
- •Participants with concurrent or history of another malignancy within 2 years of study entry Except:
- •Bowen's disease
- •Cured basal cell or cutaneous squamous cell carcinoma (CuSCC)
- •Gleason 6 prostate cancer
- •Treated in-situ carcinoma of cervix
- •Participant's conditions that contraindicates the use of study treatments and may affect interpretation of results or may render the participant at high risk from treatment complications.
- •Pregnant (confirmed by positive serum beta-human chorionic gonadotropin (ß-HCG) test), lactating or breast-feeding women.
- •Is a family member of the investigator or any associate, colleague, and employee assisting in the conduct of the study (secretary, nurse, technician).
- •Is in a position likely to represent a conflict of interest.
研究组 & 干预措施
Treatment arm (Safety Lead-in and Pivotal arm)
Experimental
Encorafenib will be administered as a fixed, flat oral dose of 450 mg QD in combination with binimetinib as a fixed, flat oral dose of 45 mg BID.
干预措施: Encorafenib (Drug)
Treatment arm (Safety Lead-in and Pivotal arm)
Experimental
Encorafenib will be administered as a fixed, flat oral dose of 450 mg QD in combination with binimetinib as a fixed, flat oral dose of 45 mg BID.
干预措施: Binimetinib (Drug)
结局指标
主要结局
Safety Lead-In (SLI) Part: Incidence of Dose-limiting toxicities (DLTs)
时间窗: Cycle 1; Each cycle is 28 days
Incidence of DLTs experienced during the Cycle 1 (days 1 to 28) after the first dose of study treatment. DLT rate defined as the number of DLT-evaluable participants with DLTs in the first 28 days after first dose of study treatment in the SLI (DLT-evaluation period), divided by the number of DLT-evaluable participants.
Pivotal Part: Confirmed objective response rate (cORR)
时间窗: Cycle 1 Day 1 through safety follow-up visit (30 days after end of treatment (EOT) visit or 7 days after EOT visit/last dose if EOT not performed), approximately up to 18 months. Each cycle is 28 days.
cORR defined as the percentage of participants who have achieved a complete response (CR) or partial response (PR) as determined by Independent Central Review (ICR) of radiographic disease assessments according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Proportion of patients who have achieved a confirmed Best Overall Response (cBOR) of CR or PR as determined by per RECIST v1.1 and corresponding exact two-sided binomial 95% Confidence interval (CI).
次要结局
- Safety Lead-In (SLI) Part: Pharmacokinetic (PK) parameter of encorafenib: Area under the curve (AUC)(Cycle 1 Day 1; Each cycle is 28 days)
- Safety Lead-In (SLI) Part: Pharmacokinetic (PK) parameter of binimetinib: Minimum serum concentration (Cmin)(Cycle 1 Day 1; Each cycle is 28 days)
- Safety Lead-In (SLI) Part: Pharmacokinetic (PK) parameter of encorafenib metabolite (LHY746): Area under the curve (AUC)(Cycle 1 Day 1; Each cycle is 28 days)
- Safety Lead-In (SLI) Part: Pharmacokinetic (PK) parameter of binimetinib metabolite (AR00426032): Area under the curve (AUC)(Cycle 1 Day 1; Each cycle is 28 days)
- Safety Lead-In (SLI) Part: Incidence, nature and severity of treatment emergent adverse events (TEAEs)(Cycle 1 Day 1 through safety follow-up visit (30 days (+/- 3 days)) after last study treatment dose or before the initiation of subsequent anticancer therapy, whichever occurs first, approximately up to 18 months. Each cycle is 28 days.)
- Safety Lead-In (SLI) Part: Pharmacokinetic (PK) parameter of encorafenib: Minimum serum concentration (Cmin)(Cycle 1 Day 1; Each cycle is 28 days)
- Safety Lead-In (SLI) Part: Pharmacokinetic (PK) parameter of encorafenib metabolite (LHY746): Minimum serum concentration (Cmin)(Cycle 1 Day 1; Each cycle is 28 days)
- Pivotal Part: Duration of Response (DOR)(Cycle 1 Day 1 through safety follow-up visit (30 days (+/- 3 days)) after last study treatment dose or before the initiation of subsequent anticancer therapy, whichever occurs first, approximately up to 18 months. Each cycle is 28 days.)
- Safety Lead-In (SLI) Part: Pharmacokinetic (PK) parameter of binimetinib metabolite (AR00426032): Minimum serum concentration (Cmin)(Cycle 1 Day 1; Each cycle is 28 days)
- Safety Lead-In (SLI) Part: Incidence of treatment emergent adverse events (TEAEs) related to notable change from baseline clinical laboratory parameter: Coagulation(Cycle 1 Day 1 through safety follow-up visit (30 days (+/- 3 days)) after last study treatment dose or before the initiation of subsequent anticancer therapy, whichever occurs first, approximately up to 18 months. Each cycle is 28 days.)
- Safety Lead-In (SLI) Part: Pharmacokinetic (PK) parameter of encorafenib: Maximum serum concentration (Cmax)(Cycle 1 Day 1; Each cycle is 28 days)
- Safety Lead-In (SLI) Part: Pharmacokinetic (PK) parameter of binimetinib: Area under the curve (AUC)(Cycle 1 Day 1; Each cycle is 28 days)
- Safety Lead-In (SLI) Part: Pharmacokinetic (PK) parameter of encorafenib metabolite (LHY746): Maximum serum concentration (Cmax)(Cycle 1 Day 1; Each cycle is 28 days)
- Safety Lead-In (SLI) Part: Pharmacokinetic (PK) parameter of binimetinib metabolite (AR00426032): Maximum serum concentration (Cmax)(Cycle 1 Day 1; Each cycle is 28 days)
- Safety Lead-In (SLI) Part: Incidence of treatment emergent adverse events (TEAEs) related to notable change from baseline of dipstick urinalysis(Cycle 1 Day 1 through safety follow-up visit (30 days (+/- 3 days)) after last study treatment dose or before the initiation of subsequent anticancer therapy, whichever occurs first, approximately up to 18 months. Each cycle is 28 days.)
- Pivotal Part: Incidence of treatment-emergent adverse events (TEAEs) related to notable or abnormal changes from baseline of echocardiogram or multigated acquisition (ECHO/MUGA) scans.(Cycle 1 Day 1 through safety follow-up visit (30 days (+/- 3 days)) after last study treatment dose or before the initiation of subsequent anticancer therapy, whichever occurs first, approximately up to 18 months. Each cycle is 28 days.)
- Pivotal Part: Pharmacokinetic (PK) parameter of encorafenib: Minimum serum concentration (Cmin)(Cycle 1 Day 1 and Cycle 2 Day 1; Cycle 1 to Cycle 6 at pre-dose; Each cycle is 28 days)
- Safety Lead-In (SLI) Part: Pharmacokinetic (PK) parameter of binimetinib: Maximum serum concentration (Cmax)(Cycle 1 Day 1; Each cycle is 28 days)
- Safety Lead-In (SLI) Part: Incidence of treatment-emergent adverse events (TEAEs) related to notable or abnormal changes in vital signs from baseline of vital sign examinations.(Cycle 1 Day 1 through safety follow-up visit (30 days (+/- 3 days)) after last study treatment dose or before the initiation of subsequent anticancer therapy, whichever occurs first, approximately up to 18 months. Each cycle is 28 days.)
- Safety Lead-In (SLI) Part: Incidence of treatment-emergent adverse events (TEAEs) related to notable or abnormal changes from baseline of 12-lead electrocardiograms (ECGs)(Cycle 1 Day 1 through safety follow-up visit (30 days (+/- 3 days)) after last study treatment dose or before the initiation of subsequent anticancer therapy, whichever occurs first, approximately up to 18 months. Each cycle is 28 days.)
- Pivotal Part: Incidence of treatment emergent adverse events (TEAEs) related to notable change from baseline clinical laboratory parameter: Hematology(Cycle 1 Day 1 through safety follow-up visit (30 days (+/- 3 days)) after last study treatment dose or before the initiation of subsequent anticancer therapy, whichever occurs first, approximately up to 18 months. Each cycle is 28 days.)
- Safety Lead-In (SLI) Part: Incidence of treatment emergent adverse events (TEAEs) related to notable change from baseline clinical laboratory parameter: Hematology(Cycle 1 Day 1 through safety follow-up visit (30 days (+/- 3 days)) after last study treatment dose or before the initiation of subsequent anticancer therapy, whichever occurs first, approximately up to 18 months. Each cycle is 28 days.)
- Safety Lead-In (SLI) Part: Incidence of treatment emergent adverse events (TEAEs) related to notable change from baseline clinical laboratory parameter: Chemistry(Cycle 1 Day 1 through safety follow-up visit (30 days (+/- 3 days)) after last study treatment dose or before the initiation of subsequent anticancer therapy, whichever occurs first, approximately up to 18 months. Each cycle is 28 days.)
- Safety Lead-In (SLI) Part: Incidence of treatment-emergent adverse events (TEAEs) related to notable or abnormal changes from baseline of echocardiogram or multigated acquisition (ECHO/MUGA) scans.(Cycle 1 Day 1 through safety follow-up visit (30 days (+/- 3 days)) after last study treatment dose or before the initiation of subsequent anticancer therapy, whichever occurs first, approximately up to 18 months. Each cycle is 28 days.)
- Pivotal Part: Confirmed Objective Response Rate (cORR)(Cycle 1 Day 1 through safety follow-up visit (30 days (+/- 3 days)) after last study treatment dose or before the initiation of subsequent anticancer therapy, whichever occurs first, approximately up to 18 months. Each cycle is 28 days.)
- Pivotal Part: Objective Response Rate (ORR)(Cycle 1 Day 1 through safety follow-up visit (30 days (+/- 3 days)) after last study treatment dose or before the initiation of subsequent anticancer therapy, whichever occurs first, approximately up to 18 months. Each cycle is 28 days.)
- Pivotal Part: Disease Control Rate (DCR)(Cycle 1 Day 1 through safety follow-up visit (30 days (+/- 3 days)) after last study treatment dose or before the initiation of subsequent anticancer therapy, whichever occurs first, approximately up to 18 months. Each cycle is 28 days.)
- Pivotal Part: Progression Free Survival (PFS)(Cycle 1 Day 1 through safety follow-up visit (30 days (+/- 3 days)) after last study treatment dose or before the initiation of subsequent anticancer therapy, whichever occurs first, approximately up to 18 months. Each cycle is 28 days.)
- Pivotal Part: Time to Progression (TTP)(Cycle 1 Day 1 through safety follow-up visit (30 days (+/- 3 days)) after last study treatment dose or before the initiation of subsequent anticancer therapy, whichever occurs first, approximately up to 18 months. Each cycle is 28 days.)
- Pivotal Part: Overall Survival (OS)(Cycle 1 Day 1 through safety follow-up visit (30 days (+/- 3 days)) after last study treatment dose or before the initiation of subsequent anticancer therapy, whichever occurs first, approximately up to 18 months. Each cycle is 28 days.)
- Pivotal Part: Pharmacokinetic (PK) parameter of encorafenib: Maximum serum concentration (Cmax)(Cycle 1 Day 1 and Cycle 2 Day 1; Cycle 1 to Cycle 6 at pre-dose; Each cycle is 28 days)
- Pivotal Part: Pharmacokinetic (PK) parameter of encorafenib metabolite (LHY746): Area under the curve (AUC)(Cycle 1 Day 1 and Cycle 2 Day 1; Cycle 1 to Cycle 6 at pre-dose; Each cycle is 28 days)
- Pivotal Part: Pharmacokinetic (PK) parameter of encorafenib metabolite (LHY746): Minimum serum concentration (Cmin)(Cycle 1 Day 1 and Cycle 2 Day 1; Cycle 1 to Cycle 6 at pre-dose; Each cycle is 28 days)
- Pivotal Part: Pharmacokinetic (PK) parameter of encorafenib metabolite (LHY746): Maximum serum concentration (Cmax)(Cycle 1 Day 1 and Cycle 2 Day 1; Cycle 1 to Cycle 6 at pre-dose; Each cycle is 28 days)
- Pivotal Part: Pharmacokinetic (PK) parameter of binimetinib metabolite (AR00426032): Minimum serum concentration (Cmin)(Cycle 1 Day 1 and Cycle 2 Day 1; Cycle 1 to Cycle 6 at pre-dose; Each cycle is 28 days)
- Pivotal Part: Incidence, nature and severity of treatment emergent adverse events (TEAEs)(Cycle 1 Day 1 through safety follow-up visit (30 days (+/- 3 days)) after last study treatment dose or before the initiation of subsequent anticancer therapy, whichever occurs first, approximately up to 18 months. Each cycle is 28 days.)
- Pivotal Part: Treatment emergent adverse events (TEAEs) leading to dose interruption, reduction and discontinuation.(Cycle 1 Day 1 through safety follow-up visit (30 days (+/- 3 days)) after last study treatment dose or before the initiation of subsequent anticancer therapy, whichever occurs first, approximately up to 18 months. Each cycle is 28 days.)
- Pivotal Part: Incidence of treatment emergent adverse events (TEAEs) related to notable change from baseline clinical laboratory parameter: Coagulation(Cycle 1 Day 1 through safety follow-up visit (30 days (+/- 3 days)) after last study treatment dose or before the initiation of subsequent anticancer therapy, whichever occurs first, approximately up to 18 months. Each cycle is 28 days.)
- Pivotal Part: Incidence of targeted treatment emergent adverse events (TEAEs) of special interest.(Cycle 1 Day 1 through safety follow-up visit (30 days (+/- 3 days)) after last study treatment dose or before the initiation of subsequent anticancer therapy, whichever occurs first, approximately up to 18 months. Each cycle is 28 days.)
- Pivotal Part: Pharmacokinetic (PK) parameter of encorafenib: Area under the curve (AUC)(Cycle 1 Day 1 and Cycle 2 Day 1 at pre-dose, and 1, 2, 4, 6 hours post-dose; Cycle 1 to Cycle 6 at pre-dose for sparse samples; Each cycle is 28 days)
- Pivotal Part: Pharmacokinetic (PK) parameter of binimetinib: Minimum serum concentration (Cmin)(Cycle 1 Day 1 and Cycle 2 Day 1; Cycle 1 to Cycle 6 at pre-dose; Each cycle is 28 days)
- Pivotal Part: Pharmacokinetic (PK) parameter of binimetinib: Maximum serum concentration (Cmax)(Cycle 1 Day 1 and Cycle 2 Day 1; Cycle 1 to Cycle 6 at pre-dose; Each cycle is 28 days)
- Pivotal Part: Incidence of treatment emergent serious adverse events (SAEs)(Cycle 1 Day 1 through safety follow-up visit (30 days (+/- 3 days)) after last study treatment dose or before the initiation of subsequent anticancer therapy, whichever occurs first, approximately up to 18 months. Each cycle is 28 days.)
- Pivotal Part: Incidence of treatment emergent adverse events (TEAEs) leading to death(Cycle 1 Day 1 through safety follow-up visit (30 days (+/- 3 days)) after last study treatment dose or before the initiation of subsequent anticancer therapy, whichever occurs first, approximately up to 18 months. Each cycle is 28 days.)
- Pivotal Part: Incidence of treatment emergent adverse events (TEAEs) related to notable change from baseline of dipstick urinalysis.(Cycle 1 Day 1 through safety follow-up visit (30 days (+/- 3 days)) after last study treatment dose or before the initiation of subsequent anticancer therapy, whichever occurs first, approximately up to 18 months. Each cycle is 28 days.)
- Pivotal Part: Incidence of treatment-emergent adverse events (TEAEs) related to notable or abnormal changes from baseline of 12-lead electrocardiograms (ECGs)(Cycle 1 Day 1 through safety follow-up visit (30 days (+/- 3 days)) after last study treatment dose or before the initiation of subsequent anticancer therapy, whichever occurs first, approximately up to 18 months. Each cycle is 28 days.)
- Pivotal Part: Incidence of treatment emergent adverse events (TEAEs) related to notable change from baseline clinical laboratory parameter: Chemistry(Cycle 1 Day 1 through safety follow-up visit (30 days (+/- 3 days)) after last study treatment dose or before the initiation of subsequent anticancer therapy, whichever occurs first, approximately up to 18 months. Each cycle is 28 days.)
- Pivotal Part: Incidence of treatment-emergent adverse events (TEAEs) related to notable or abnormal changes in vital signs from baseline of vital sign examinations.(Cycle 1 Day 1 through safety follow-up visit (30 days (+/- 3 days)) after last study treatment dose or before the initiation of subsequent anticancer therapy, whichever occurs first, approximately up to 18 months. Each cycle is 28 days.)
- Pivotal Part: Pharmacokinetic (PK) parameter of binimetinib metabolite (AR00426032): Maximum serum concentration (Cmax)(Cycle 1 Day 1 and Cycle 2 Day 1; Cycle 1 to Cycle 6 at pre-dose; Each cycle is 28 days)
- Pivotal Part: Pharmacokinetic (PK) parameter of binimetinib: Area under the curve (AUC)(Cycle 1 Day 1 and Cycle 2 Day 1; Cycle 1 to Cycle 6 at pre-dose; Each cycle is 28 days)
- Pivotal Part: Pharmacokinetic (PK) parameter of binimetinib metabolite (AR00426032): Area under the curve (AUC)(Cycle 1 Day 1 and Cycle 2 Day 1; Cycle 1 to Cycle 6 at pre-dose; Each cycle is 28 days)
研究者
研究点 (59)
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