A Phase Ib/II, Open-label Study of LJM716 in Combination With BYL719 Compared to Taxane or Irinotecan in Patients With Previously Treated Esophageal Squamous Cell Carcinoma (ESCC)
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 48
- 试验地点
- 4
- 主要终点
- Phase II primary outcome measure: Progression free survival (PFS)
研究概览
简要总结
To study the safety and efficacy of the combination of LJM716 and BYL719 against currently available treatments of physician's choice in previously treated esophageal squamous cell carcinoma patients.
详细描述
The study design included a Phase 1b dose escalation portion to define the maximum tolerated dose (MTD)/recommended phase 2 dose (RP2D) for the combination of LJM716 and alpelisib, followed by an open-label, randomized Phase 2 part to compare anti-tumor activity of LJM716-alpelisib combination versus physician's choice of second-line therapy (paclitaxel, docetaxel, irinotecan). However, the phase 2 part was not conducted as the study was terminated early due to limited anti-tumor activity with LJM716-alpelisib combination observed in phase 1b.
研究设计
- 研究类型
- Interventional
- 分配方式
- 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
- •Histologically confirmed esophageal squamous cell carcinoma (ESCC)
- •No more than one prior chemotherapy regimen for recurrent or metastatic ESCC (for Phase II only).
- •Progression during or after platinum-based therapy for recurrent or metastatic ESCC, or recurrence within 6 months of platinum-based chemotherapy or chemoradiotherapy for localized disease.
排除标准
- •Patients who received prior phosphoinositide-3-kinase (PI3K) inhibitor or anti-receptor tyrosine-protein kinase erbB-3 (ERBB3 or HER3) antibody treatment, including bi-specific antibodies with HER3 as one of the targets (patients with prior exposure to pertuzumab or epidermal growth factor receptor (EGFR)-targeted agents are eligible)
- •Patients who do not have an archival or fresh tumor sample (or sections of it) available or readily obtainable.
- •Patients with central nervous system (CNS) metastatic involvement.
- •Patients who have received prior systemic anti-cancer treatment, such as cyclical chemotherapy or biological therapy within a period of time that is shorter than the cycle length used for that treatment (e.g. 6 weeks for nitrosourea, mitomycin-C) prior to starting study treatment.
- •Patients who have received definitive radiotherapy ≤ 4 weeks prior to starting study drug, who have not recovered from side effects of such therapy and/or from whom ≥ 30% of the bone marrow was irradiated.
- •Other protocol-defined inclusion/exclusion criteria may apply.
研究组 & 干预措施
LJM716-BYL719 arm
approximately 42 previously treated esophageal squamous cell carcinoma (ESCC) patients will be enrolled to the LJM716-BYL719 combination arm to evaluate the anti-tumor activity and further assess the safety, tolerability and anti-tumor activity of the combination versus current therapies (physician's choice of paclitaxel, docetaxel or irinotecan).
干预措施: LJM716 (Drug)
LJM716-BYL719 arm
approximately 42 previously treated esophageal squamous cell carcinoma (ESCC) patients will be enrolled to the LJM716-BYL719 combination arm to evaluate the anti-tumor activity and further assess the safety, tolerability and anti-tumor activity of the combination versus current therapies (physician's choice of paclitaxel, docetaxel or irinotecan).
干预措施: BYL719 (Drug)
Paclitaxel, Docetaxel or Irinotecan arm
approximately 42 previously treated esophageal squamous cell carcinoma (ESCC) patients will be enrolled to the Paclitaxel, Docetaxel or Irinotecan arm (physician's choice arm) to evaluate the anti-tumor activity and further assess the safety, tolerability and anti-tumor activity of the LJM716-BYL719 combination versus current therapies (physician's choice of paclitaxel, docetaxel or irinotecan).
干预措施: Irinotecan (Drug)
Paclitaxel, Docetaxel or Irinotecan arm
approximately 42 previously treated esophageal squamous cell carcinoma (ESCC) patients will be enrolled to the Paclitaxel, Docetaxel or Irinotecan arm (physician's choice arm) to evaluate the anti-tumor activity and further assess the safety, tolerability and anti-tumor activity of the LJM716-BYL719 combination versus current therapies (physician's choice of paclitaxel, docetaxel or irinotecan).
干预措施: Paclitaxel (Drug)
Paclitaxel, Docetaxel or Irinotecan arm
approximately 42 previously treated esophageal squamous cell carcinoma (ESCC) patients will be enrolled to the Paclitaxel, Docetaxel or Irinotecan arm (physician's choice arm) to evaluate the anti-tumor activity and further assess the safety, tolerability and anti-tumor activity of the LJM716-BYL719 combination versus current therapies (physician's choice of paclitaxel, docetaxel or irinotecan).
干预措施: Docetaxel (Drug)
结局指标
主要结局
Phase II primary outcome measure: Progression free survival (PFS)
时间窗: Every 6 weeks from the date of the baseline computed-tomography (CT) scan until the date of first documented evidence of disease progression or date of death, whichever comes first, assessed up to 24 months.
Progression-free survival is the time from date of start of treatment to the date of event defined as the first documented progression or death due to any cause. If a patient has not had an event, progression-free survival is censored at the date of last adequate assessment.
Phase Ib primary outcome measure: Incidence rate of dose limiting toxicities (DLTs).
时间窗: approximately 8 months
The open-label dose escalation part of the study will be guided by a well-established statistical method/model to estimate the maximum tolerated dose(s) and/or Recommended Phase II Dose (s) guided by the safety (incidence of dose limiting toxicities), efficacy, pharmacokinetics and pharmacodynamics data.
次要结局
- Overall survival (OS) per RECIST 1.1 (for Ph 1b )(Every 21 days from the date of the baseline computed tomography (CT) scan until the end of treatment visit (about 4 months))
- Progression free survival (PFS) per RECIST 1.1 (Ph 1b )(Every 21 days from the date of the baseline computed tomography (CT) scan until the end of study visit (about 5 months))
- Safety and tolerability of the LJM716-BYL719(Every 21 days from the date of the baseline visit until the end of study visit (about 5 months))
- Best overall response (BOR), per RECIST 1.1 (Ph 1b )(Every 21 days from the date of baseline computed tomography (CT) scan until end of treatment visit (about 4 months))
- Overall response rate (ORR) per RECIST 1.1 (Ph 1b )(Every 21 days from the date of the baseline computed tomography (CT) scan until the end of treatment visit (about 4 months))
- Duration of response (DOR) per RECIST 1.1 (Ph 1b )(Every 21 days from the date of the baseline computed tomography (CT) scan until the end of treatment visit (about 4 months))
- Disease control rate (DCR) per RECIST 1.1 (Ph 1b )(Every 21 days from the date of the baseline computed tomography (CT) scan until the end of treatment visit (about 4 months))
- Plasma concentration versus time profiles Plasma PK parameters of LJM716, BYL719(Baseline, 2hr,4hr,8hr,24hr,48hr,96hr, 168 hr, every 21 days for 10 cycles (21 days each) and at end of treatment (about 4 months))