A Phase 2, Open-label Study of Encorafenib + Binimetinib in Patients With BRAFV600-mutant Non-small Cell Lung Cancer
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- Pfizer
- 入组人数
- 98
- 试验地点
- 227
- 主要终点
- Percentage of Participants With Confirmed Objective Response (OR) as Determined by Independent Radiology Review (IRR)
研究概览
简要总结
This is an open-label, multicenter, non-randomized, Phase 2 study to determine the safety, tolerability and efficacy of encorafenib given in combination with binimetinib in patients with BRAFV600E-mutant metastatic non-small cell lung cancer (NSCLC). Patients who are either treatment-naïve, OR who have received 1) first-line treatment with standard platinum-based chemotherapy, OR 2) first-line treatment with an anti-programmed cell death protein 1 (PD-1)/programmed cell death protein ligand 1 (PD-L1) inhibitor given alone or in combination with platinum-based chemotherapy will be enrolled.
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
- •Histologically confirmed diagnosis of non-small cell lung cancer (NSCLC) that is currently Stage IV.
- •Presence of a BRAFV600E mutation in lung cancer tissue as determined by a local laboratory assay or the presence of other BRAFV600 mutations other than V600E (i.e. K or D) will be considered
- •Patients who are either treatment-naïve (e.g., no prior systemic therapy for advanced/metastatic disease), OR who have received 1) first-line platinum-based chemotherapy OR 2) first-line treatment with an anti-programmed cell death protein 1 (PD-1)/ programmed cell death protein ligand 1(PD-L1) inhibitor given alone or in combination with platinum-based chemotherapy.
- •Presence of measurable disease based on Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1).
- •Eastern Cooperation Oncology Group (ECOG) performance status of 0 or
- •Adequate bone marrow function characterized by the following at screening:
- •absolute neutrophil count (ANC) ≥ 1.5 × 10⁹/L;
- •Platelets ≥ 100 × 10⁹/L;
- •Hemoglobin ≥ 8.5 g/dL (with or without blood transfusions).
- •Adequate hepatic and renal function characterized by the following at screening:
- •Total bilirubin ≤ 1.5 × upper limit of normal (ULN)
- •alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 × ULN, or ≤ 5 × ULN in presence of liver metastases; Serum creatinine ≤ 1.5 × ULN; or calculated creatinine clearance ≥ 50 mL/min by Cockcroft-Gault formula; or estimated glomerular filtration rate > 50 mL/min/1.73m².
排除标准
- •Patients who have documentation of any of the following:
- •epidermal growth factor receptor (EGFR) mutation
- •anaplastic lymphoma kinase (ALK) fusion oncogene or
- •ROS1 rearrangement
- •Patients who have received more than 1 prior line of systemic therapy in the advanced/metastatic setting.
- •Previous treatment with any BRAF inhibitor (e.g., dabrafenib, vemurafenib, XL281/BMS-908662, etc.), or any mitogen-activated protein kinase (MEK) inhibitor (e.g., trametinib, cobimetinib, selumetinib, RDEA119, etc.) prior to screening and enrollment.
- •Impaired cardiovascular function or clinically significant cardiovascular diseases
- •History of thromboembolic or cerebrovascular events ≤ 12 weeks prior to the first dose of study treatment. Examples include transient ischemic attacks, cerebrovascular accidents, hemodynamically significant (i.e. massive or sub-massive) deep vein thrombosis or pulmonary emboli.
- •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 syndromes); history of retinal degenerative disease.
- •Concurrent neuromuscular disorder that is associated with the potential of elevated creatine (phospho)kinase (CK) (e.g., inflammatory myopathies, muscular dystrophy, amyotrophic lateral sclerosis, spinal muscular atrophy).
- •Patients with symptomatic brain metastasis, leptomeningeal disease or other active central nervous system (CNS) metastases are not eligible.
研究组 & 干预措施
Treatment Period
Study treatment with encorafenib and binimetinib will be self-administered orally without regard to food.
Patients will receive the following per 28-day (± 3 days) cycle:
- Encorafenib: 450 mg (6 × 75 mg capsule) once daily (QD)
- Binimetinib: 45 mg (3 × 15 mg tablet) twice daily (BID)
干预措施: encorafenib (Drug)
Treatment Period
Study treatment with encorafenib and binimetinib will be self-administered orally without regard to food.
Patients will receive the following per 28-day (± 3 days) cycle:
- Encorafenib: 450 mg (6 × 75 mg capsule) once daily (QD)
- Binimetinib: 45 mg (3 × 15 mg tablet) twice daily (BID)
干预措施: binimetinib (Drug)
结局指标
主要结局
Percentage of Participants With Confirmed Objective Response (OR) as Determined by Independent Radiology Review (IRR)
时间窗: From date of the first dose of study intervention until documented progressive disease (PD) or start of new anticancer therapy (up to 36 months)
Objective Response Rate (ORR) was defined as the percentage of participants who had achieved a confirmed best overall response (Complete Response \[CR\] or Partial Response \[PR\]) per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Both CR and PR must be confirmed by repeat assessments performed no less than 4 weeks after the criteria for response were first met. CR was defined by the disappearance of all non-lymph node target lesions (where all target lesions were recorded with a length of 0 mm, and any pathological lymph nodes \[recorded as target lesion\] must have reduction in short axis to \<10 mm) and complete disappearance of all non-target lesions (where all non-target lesions were marked "Absent", and all lymph nodes must be non-pathological in size \[\<10 mm in short axis\]). PR was defined by a 30% or more decrease in sum of diameters (SOD) of target lesions, taking as reference the baseline SOD. ORR was calculated with the exact 2-sided Clopper-Pearson 95% CI.
次要结局
- Percentage of Participants With Confirmed Objective Response (OR) by Investigator Assessment(From date of the first dose of study intervention until documented PD or start of new anticancer therapy (up to 36 months))
- Time to Response (TTR) by IRR and Investigator Assessments(From the date of first dose to the first documentation of confirmed objective response (CR or PR) (up to 36 months))
- Duration of Response (DoR) by IRR and Investigator Assessments(From the date of the first confirmed documented response (CR or PR) to the earliest date of disease progression or death due to any cause (up to 36 months))
- Disease Control Rate (DCR) by IRR and Investigator Assessments(After 24 Weeks (≥168 days) from the date of first dose of study intervention)
- Progression-free Survival (PFS) by IRR and Investigator Assessments(From the date of first dose of study drug to the earliest date of disease progression, or death due to any cause (up to 36 months))
- Kaplan-Meier Estimates of Overall Survival (OS)(The time from the date of first dose of study intervention to the date of death due to any cause (up to 36 months))
- Number of Participants With Treatment-Emergent Adverse Events (TEAEs)(From the time the participant provided informed consent, through and including a minimum of 30 calendar days, after the last administration of the study intervention, and the safety follow-up visit (30 days [±7 days] after the EOT visit) (up to 36 months))
- Number of Participants With Shifts From Grade ≤2 at Baseline to Grade 3 or 4 at Post-baseline in Chemistry Laboratory Test Values Based on CTCAE Grade(Screening, Cycle 1 Day 1, Cycle 2 Day 1 ±3 Days, Day 1 ±3 Days in Subsequent Cycles, EOT ±3 Days and Safety Follow-up Visit (30 Days [±7 Days] After the EOT Visit) (Up to 36 Months))
- Number of Participants With Notable ECG (QTcF) Values(Screening, Cycle 1 Day 1, Cycle 2 Day 1 ±3 Days, Every 12 Weeks ±7 Days, and EOT ±3 Days (Up to 36 Months))
- Number of Participants With Shifts From Grade ≤2 at Baseline to Grade 3 or 4 at Post-baseline in Hematology Laboratory Test Values Based on CTCAE Grade(Screening, Cycle 1 Day 1, Cycle 2 Day 1 ±3 Days, Day 1 ±3 Days in Subsequent Cycles, End of Treatment (EOT) ±3 Days and Safety Follow-up Visit (30 Days [±7 Days] After the EOT Visit) (Up to 36 Months))
- Number of Participants With Notable Abnormal Vital Signs(Screening, Cycle 1 Day 1, Cycle 2 Day 1 ±3 Days, Day 1 ±3 Days of Subsequent Cycles, EOT ±3 Days, and Safety Follow-up Visit (30 Days [±7 Days] After the EOT Visit) (Up to 36 Months))
- Number of Participants With the Worst Post-baseline Left Ventricular Ejection Fraction (LVEF) Values Based on CTCAE Grade(Screening, Cycle 2 Day 1 ±3 Days, Every 12 Weeks ±7 Days, and EOT ±3 Days (Up to 36 Months))