NCT05003622已完成1 期
Multicenter, Open-label, Phase 1 Study Investigating the Safety and Tolerability of Encorafenib Monotherapy in BRAF V600E-mutated Chinese Patients With Advanced Metastatic Solid Tumors
适应症
干预措施
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 3
- 试验地点
- 1
- 主要终点
- Dose Limiting Toxicities (DLTs) Experienced During Cycle 1
研究概览
简要总结
This is a phase 1, multicenter, open-label, single-arm study to investigate the safety and tolerability of encorafenib 300 mg once daily (QD) monotherapy in adult Chinese participants with B-RAF Proto-oncogene, Serine/threonine Kinase V600E (BRAF V600E) mutant advanced solid tumors (unresectable metastatic melanoma or metastatic non-small cell lung cancer (NSCLC)), who are BRAF-inhibitor treatment-naïve and have failed the previous therapy(ies) in the metastatic setting or are not eligible to standard therapy. Participants will be eligible for the study based on identification of a BRAF V600E mutation in tumor tissue by a local National Medical Products Administration (NMPA) approved assay obtained prior to screening.
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
- •Provide a signed and dated informed consent form (ICF).
- •Chinese male or female with age ≥18 years old at the time of the informed consent.
- •Documented histology- and/or cytology-confirmed metastatic melanoma or non-small cell lung cancer (NSCLC) (i.e. adenocarcinoma, large cell carcinoma, squamous cell carcinoma).
- •Presence of B-RAF Proto-oncogene, Serine/threonine Kinase V600E Mutant (BRAF V600E) mutation as determined by a local laboratory with a National Medical Products Administration (NMPA) approved BRAF test.
- •BRAF inhibitor treatment-naïve participants and having failed the previous therapy(ies) for metastatic disease or are not eligible to standard therapy.
- •At least one tumor lesion as per investigator assessment according to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1, which has neither been irradiated nor biopsied during the screening period. The irradiated lesion is acceptable only if it is proven as disease progression deemed measurable prior to study.
- •Life expectancy ≥3 months.
- •Eastern Co-operative 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, or are surgically sterile for at least 6 weeks, or women of childbearing potential (WOCBP) must agree to take appropriate precautions to avoid pregnancy.
- •Men must agree not to father child until 90 days after the last dose of study treatment.
排除标准
- •Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to encorafenib, or its excipients.
- •For metastatic NSCLC: documented anaplastic lymphoma kinase (ALK) fusion oncogene, ROS1 (c-ros oncogene 1) rearrangement or epidermal growth factor receptor (EGFR) sensitizing or driver mutation.
- •Receipt of anticancer medications or investigational drugs within intervals before the first administration of study treatment.
- •Symptomatic brain metastasis.
- •Leptomeningeal disease.
- •Participant has not recovered to ≤Grade 1 from toxic effects of prior therapy and/or complications from prior surgical treatment 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.
- •Participants with active Hepatitis B virus (HBV) or Hepatitis C virus (HCV) or any other severe viral active infection (e.g. severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2] infection).
- •Evidence of active, non-infectious pneumonitis, history of interstitial lung disease that required oral or intravenous glucocorticoid steroids 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.
- •Previous or concurrent malignancy within 2 years of study entry.
- •Bowen's disease.
- •Cured basal cell or squamous cell skin cancer.
- •Gleason 6 prostate cancer.
- •Treated in-situ carcinoma of cervix.
- •Participant's conditions that contraindicates the use of study treatment and may affect interpretation of results or that 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
encorafenib
Experimental
Encorafenib hard capsule will be orally self-administered. A fixed-flat dose of 300 mg (4 x 75 mg) Per Oral (PO) encorafenib will be administered once-daily (QD).
干预措施: Encorafenib (Drug)
结局指标
主要结局
Dose Limiting Toxicities (DLTs) Experienced During Cycle 1
时间窗: At the end of Cycle 1. Each cycle was 28 days.
The primary endpoint was the number of patients experiencing dose limiting toxicity (DLT) occurring within the first 28 days of study treatment (Cycle 1). A DLT was defined as any adverse event or abnormal laboratory value assessed as unrelated to disease, disease progression, intercurrent illness or concomitant medications/therapies resulting in the inability to tolerate at least 75% dose intensity \[(administered dose in mg/planned dose in mg) × 100\] that satisfied at least one of the prespecified criteria.
次要结局
- Plasma Pharmacokinetics (PK) of Encorafenib: ARAUC After Single and Repeated Administration of Encorafenib(at steady state after 1 month treatment (Cycle 2 Day 1). Each cycle was 28 days.)
- Plasma Pharmacokinetics (PK) of Encorafenib Metabolite (LHY746): Maximum Concentration (Cmax) After Single and Repeated Administration of Encorafenib(First day of treatment (Cycle 1 Day 1) and at steady state after 1 month treatment (Cycle 2 Day 1). Each cycle was 28 days.)
- Occurrence of Treatment Emergent Adverse Events (TEAEs)(Cycle 1 Day 1 through safety follow-up visit (30 days after end of treatment (EOT) visit or 7 days after end EOT visit/last dose if EOT not performed), approximately up to 6 months. Each cycle was 28 days.)
- Notable Change From Baseline of Blood Clinical Chemistry Parameters(Screening (Days -28 to -1), Cycle 1 Day 1 (if not done within 72 hours before the first dose), Cycle 1 Day 15, on Day 1 each subsequent cycle, end of treatment visit 30 day safety follow up visit, approximately up to 6 months. Each cycle was 28 days.)
- Plasma Pharmacokinetics (PK) of Encorafenib Metabolite (LHY746): Time Taken to Reach Maximum Concentration (Tmax) After Single and Repeated Administration of Encorafenib Metabolite (LHY746)(First day of treatment (Cycle 1 Day 1) and at steady state after 1 month treatment (Cycle 2 Day 1). Each cycle was 28 days.)
- Notable Change From Baseline of Coagulation Parameters(Screening (Days -28 to -1), Cycle 1 Day 1 (if not done within 72 hours before the first dose), Cycle 1 Day 15, on Day 1 each subsequent cycle, end of treatment visit 30 day safety follow up visit, approximately up to 6 months. Each cycle was 28 days.)
- Notable or Abnormal Changes in Vital Signs From Baseline of Vital Sign Examinations.(Screening (Days -28 to -1), Cycle 1 Days 1, 8, 15 and 22, Day 1 of each subsequent cycle, the end of treatment visit and the 30-day safety follow-up visit, approximately up to 6 months. Each cycle was 28 days.)
- Occurrence of Targeted Treatment Emergent Adverse Events (TEAEs) of Special Interest(Cycle 1 Day 1 through safety follow-up visit (30 days after end of treatment [EOT] visit or 7 days after end EOT visit/last dose if EOT not performed), approximately up to 6 months.)
- Notable Change From Baseline of Blood Hematology Parameters: Hemoglobin, Leukocytes, Neutrophils, Platelets, Lymphocytes.(Screening (Days -28 to -1), Cycle 1 Day 1 (if not done within 72 hours before the first dose), Cycle 1 Day 15, on Day 1 each subsequent cycle, end of treatment visit 30 day safety follow up visit, approximately up to 6 months. Each cycle was 28 days.)
- Notable Change From Baseline of Dipstick Urinalysis(Days -28 to -1, Cycle1 Day1 (if not within 72 hours before first dose),Cycle1 Day15,on Day1 each subsequent cycle,end of treatment visit 30 day safety follow up visit, up to 6 months. Additional urinalysis in Cycle 1 Days 8 and 22. Each cycle was 28 days.)
- Plasma Pharmacokinetics (PK) of Encorafenib: Area Under the Curve (AUC) After Single and Repeated Administration of Encorafenib(First day of treatment (Cycle 1 Day 1) and at steady state after 1 month treatment (Cycle 2 Day 1). Each cycle was 28 days.)
- Plasma Pharmacokinetics (PK) of Encorafenib: Maximum Concentration (Cmax) After Single and Repeated Administration of Encorafenib(First day of treatment (Cycle 1 Day 1) and at steady state after 1 month treatment (Cycle 2 Day 1). Each cycle was 28 days.)
- Plasma Pharmacokinetics (PK) of Encorafenib: Minimum Concentration (Cmin) After Single and Repeated Administration of Encorafenib(First day of treatment (Cycle 1 Day 1) and at steady state after 1 month treatment (Cycle 2 Day 1). Each cycle was 28 days.)
- Plasma Pharmacokinetics (PK) of Encorafenib Metabolite (LHY746): Minimum Concentration (Cmin) After Single and Repeated Administration of Encorafenib(First day of treatment (Cycle 1 Day 1) and at steady state after 1 month treatment (Cycle 2 Day 1). Each cycle was 28 days.)
- Notable or Abnormal Changes From Baseline of 12-lead Electrocardiograms (ECGs)(Screening (Days -28 to -1), Cycle 1 Day 8, 15 and 22, Day 1 of each subsequent even cycle, and the end of treatment visit, approximately up to 6 months. Each cycle was 28 days.)
- Plasma Pharmacokinetics (PK) of Encorafenib: Time Taken to Reach Maximum Concentration (Tmax) After Single and Repeated Administration of Encorafenib(First day of treatment (Cycle 1 Day 1) and at steady state after 1 month treatment (Cycle 2 Day 1). Each cycle was 28 days.)
- Plasma Pharmacokinetics (PK) of Encorafenib Metabolite (LHY746): Area Under the Curve (AUC) After Single and Repeated Administration of Encorafenib Metabolite (LHY746)(First day of treatment (Cycle 1 Day 1) and at steady state after 1 month treatment (Cycle 2 Day 1). Each cycle was 28 days.)
- Plasma Pharmacokinetics (PK) of Encorafenib Metabolite (LHY746): ARAUC After Single and Repeated Administration of Encorafenib Metabolite (LHY746)(at steady state after 1 month treatment (Cycle 2 Day 1). Each cycle was 28 days.)
- Plasma Pharmacokinetics (PK) of Encorafenib Metabolite (LHY746): MRAUC After Single and Repeated Administration of Encorafenib Metabolite (LHY746)(First day of treatment (Cycle 1 Day 1) and at steady state after 1 month treatment (Cycle 2 Day 1). Each cycle was 28 days.)
研究者
研究点 (1)
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