A Phase Ib/II Multi-center, Open-label, Dose Escalation Study of LGX818 and Cetuximab or LGX818, BYL719, and Cetuximab in Patients With BRAF Mutant Metastatic Colorectal Cancer
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- Pfizer
- 入组人数
- 156
- 试验地点
- 41
- 主要终点
- Phase 1b: Number of Participants With Incidence of Dose Limiting Toxicities (DLTs): Cycle 1
研究概览
简要总结
This study will assess the safety and efficacy of LGX818 when combined with cetuximab or combined with cetuximab and BYL719 in patients with BRAF mutant metastatic colorectal cancer
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 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
- •Metastatic colorectal cancer
- •Progression after at least one prior standard of care regimen or be intolerant to irinotecan-based regimens
- •Life expectancy ≥ 3 months
- •ECOG performance status ≤ 2
排除标准
- •Symptomatic or untreated leptomeningeal disease
- •Symptomatic brain metastasis
- •Patients with clinically manifested diabetes
- •Acute or chronic pancreatitis
- •Clinically significant cardiac disease
- •Other protocol-defined inclusion/exclusion criteria may apply.
研究组 & 干预措施
LGX818 + cetuximab
干预措施: LGX818 (Drug)
LGX818 + cetuximab
干预措施: Cetuximab (Drug)
LGX818 + BYL719 + cetuximab
干预措施: LGX818 (Drug)
LGX818 + BYL719 + cetuximab
干预措施: Cetuximab (Drug)
LGX818 + BYL719 + cetuximab
干预措施: BYL719 (Drug)
结局指标
主要结局
Phase 1b: Number of Participants With Incidence of Dose Limiting Toxicities (DLTs): Cycle 1
时间窗: Cycle 1: Day 1 to Day 28
DLTs were defined as an adverse event (AE) or abnormal laboratory value assessed as unrelated to disease, disease progression, inter-current illness, or concomitant medications that occurred within the first 28 days of treatment and meets any of the criteria included blood and lymphatic system disorders, investigations (blood, renal, hepatic, metabolic), skin and subcutaneous tissue disorders: rash, HFSR (hand foot skin reaction) and/or photosensitivity, metabolism and nutrition disorders: hyperglycemia, gastrointestinal disorders, cardiac disorders, vascular disorders, general disorders and administration site conditions, tumor lysis syndrome, ophthalmologic and other adverse events: study drug-related fever, alkaline phosphatase elevation.
Phase 2: Progression Free Survival (PFS)
时间窗: From the date of randomization until the first documentation of disease progression or death due to any cause, censored date, whichever occurred first (maximum up to 43 months)
PFS was defined as the time from the date of randomization to the date of the first documented disease progression or death due to any cause. Participants who did not progress per RECIST (Response Evaluation Criteria in Solid Tumors) version (v) 1.1, were not known to have died prior to the data cut-off, or received any further anticancer therapy were censored at the date of last adequate tumor assessment or the anticancer therapy date, whichever was earlier.
次要结局
- Apparent Total Plasma Clearance at Steady State (CL/F, ss) of BYL719 (Alpelisib)(Cycle 1 Day 8, Cycle 2 Day 1: Pre-dose, 0.5, 1, 2, 4, 6, 8 and 24 +/- 2 hours post-dose)
- Apparent Terminal Volume of Distribution (Vz/F) of LGX818 (Encorafenib)(Cycle 1 Day 1: Pre-dose, 0.5, 1, 2, 4, 6, 8 and 24 +/- 2 hours post-dose)
- Time to Reach Maximum Observed Plasma Concentration (Tmax) of LGX818 (Encorafenib)(Cycle 1 Day 1: Pre-dose, 0.5, 1, 2, 4, 6, 8 and 24 +/- 2 hours post-dose)
- Apparent Total Plasma Clearance at Steady State (CL/F, ss) of LGX818 (Encorafenib)(Cycle 1 Day 8, Cycle 2 Day 1: Pre-dose, 0.5, 1, 2, 4, 6, 8 and 24 +/- 2 hours post-dose)
- Number of Participants With Treatment - Emergent Adverse Events of Grade 3 or 4 Severity Based on National Cancer Institute of Common Terminology Criteria (NCI-CTCAE), Version 4.0(From screening up to 30 days after the last dose of study treatment (for a maximum duration of 43 months, approximately))
- Apparent Total Plasma Clearance (CL/F) of LGX818 (Encorafenib)(Cycle 1 Day 1: Pre-dose, 0.5, 1, 2, 4, 6, 8 and 24 +/- 2 hours post-dose)
- Apparent Total Plasma Clearance (CL/F) of BYL719 (Alpelisib)(Cycle 1 Day 1: Pre-dose, 0.5, 1, 2, 4, 6, 8 and 24 +/- 2 hours post-dose)
- Apparent Terminal Volume of Distribution at Steady State (Vz/F, ss) of LGX818 (Encorafenib)(Cycle 1 Day 8, Cycle 2 Day 1: Pre-dose, 0.5, 1, 2, 4, 6, 8 and 24 +/- 2 hours post-dose)
- Apparent Terminal Volume of Distribution (Vz/F) of BYL719 (Alpelisib)(Cycle 1 Day 1: Pre-dose, 0.5, 1, 2, 4, 6, 8 and 24 +/- 2 hours post-dose)
- Time to Reach Maximum Plasma Concentration at Steady State (Tmax, ss) of LGX818 (Encorafenib)(Cycle 1 Day 8, Cycle 2 Day 1: Pre-dose, 0.5, 1, 2, 4, 6, 8 and 24 +/- 2 hours post-dose)
- Apparent Terminal Volume of Distribution at Steady State (Vz/F, ss) of BYL719 (Alpelisib)(Cycle 1 Day 8, Cycle 2 Day 1: Pre-dose, 0.5, 1, 2, 4, 6, 8 and 24 +/- 2 hours post-dose)
- Time to Reach Maximum Observed Plasma Concentration (Tmax) of BYL719 (Alpelisib)(Cycle 1 Day 1: Pre-dose, 0.5, 1, 2, 4, 6, 8 and 24 +/- 2 hours post-dose)
- Time of Last Observed Plasma Concentration (T-last) of BYL719 (Alpelisib)(Cycle 1 Day 1: Pre-dose, 0.5, 1, 2, 4, 6, 8 and 24 +/- 2 hours post-dose)
- Time to Reach Maximum Plasma Concentration at Steady State (Tmax, ss) of BYL719 (Alpelisib)(Cycle 1 Day 8, Cycle 2 Day 1: Pre-dose, 0.5, 1, 2, 4, 6, 8 and 24 +/- 2 hours post-dose)
- Time of Last Observed Plasma Concentration (T-last) of LGX818 (Encorafenib)(Cycle 1 Day 1: Pre-dose, 0.5, 1, 2, 4, 6, 8 and 24 +/- 2 hours post-dose)
- Duration of Response (DOR)(From the first documentation of OR (confirmed CR or PR) to first documentation of PD/death due to any cause or censoring date, whichever occurred first (up to 43 months))
- Time to Response (TTR)(From the date of randomization or date of start of treatment until first documented response (CR or PR) or data censoring date, whichever occurred first (maximum up to 43 months))
- Time of Last Observed Plasma Concentration at Steady State (T-last, ss) of LGX818 (Encorafenib)(Cycle 1 Day 8, Cycle 2 Day 1: Pre-dose, 0.5, 1, 2, 4, 6, 8 and 24 +/- 2 hours post-dose)
- Time of Last Observed Plasma Concentration at Steady State (T-last, ss) of BYL719 (Alpelisib)(Cycle 1 Day 8, Cycle 2 Day 1: Pre-dose, 0.5, 1, 2, 4, 6, 8 and 24 +/- 2 hours post-dose)
- Plasma Trough Concentration at Steady State (Ctrough, ss) of LGX818 (Encorafenib)(Cycle 2 Day 1: Pre-dose, 0.5, 1, 2, 4, 6, 8 and 24 +/- 2 hours post-dose)
- Plasma Trough Concentration at Steady State (Ctrough, ss) of BYL719 (Alpelisib)(Cycle 2 Day 1: Pre-dose, 0.5, 1, 2, 4, 6, 8 and 24 +/- 2 hours post-dose)
- Overall Survival (OS)(From the date of randomization or date of start of treatment to the date of death due to any cause or data censoring date, whichever occurred first (up to 43 months))
- Phase 1b: Progression Free Survival (PFS)(From date of start of treatment to the date of event defined as the first documented progression or death due to any cause, censored date, whichever occurred first (maximum up to 43 months))
- Phase 2: Number of Participants With Any Variant in Gene Status at Baseline(Baseline (Day 1))
- Overall Response Rate (ORR)(From date of randomization or date of start of treatment until date of first documentation of PD or death due to any cause (maximum up to 43 months))