TIGER-3: A Phase 3, Open-label, Multicenter, Randomized Study of Oral Rociletinib (CO-1686) Monotherapy Versus Single-agent Cytotoxic Chemotherapy in Patients With Mutant EGFR Non-small Cell Lung Cancer (NSCLC) After Failure of at Least 1 Previous EGFR-directed Tyrosine Kinase Inhibitor (TKI) and Platinum-doublet Chemotherapy
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 入组人数
- 149
- 试验地点
- 80
- 主要终点
- Progression Free Survival (PFS) According to RECIST Version 1.1 as Determined by Investigator Review (invPFS)
研究概览
简要总结
The purpose of this study is to compare the anti-tumor efficacy of oral single-agent rociletinib, as measured by investigator assessment of the PFS, with that of single-agent cytotoxic chemotherapy in patients with EGFR-mutated, advanced/metastatic NSCLC after failure of at least 1 previous EGFR-directed TKI and at least 1 line of platinum-containing doublet chemotherapy.
详细描述
This is a Phase 3, randomized, open-label, multicenter study evaluating the safety and efficacy of oral rociletinib at 500 mg BID and 625 mg BID compared with that of single-agent cytotoxic chemotherapy, in patients with previously treated mutant EGFR NSCLC. Eligible patients are those with mutant EGFR NSCLC previously treated with at least 1 EGFR inhibitor and at least 1 line of platinum-containing chemotherapy doublet for advanced/metastatic NSCLC.
After providing informed consent to participate and screening to confirm eligibility, patients will be randomized 1:1:1 to receive either oral rociletinib 500 mg BID, oral rociletinib 625 mg BID, or single-agent cytotoxic chemotherapy (investigator choice of pemetrexed, gemcitabine, docetaxel, or paclitaxel; choice of chemotherapy agent must be specified before randomization).
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
- •All patients must meet all of the following inclusion criteria:
- •Histologically or cytologically confirmed metastatic or unresectable locally advanced NSCLC with radiological progression on the most recent therapy received
- •Documented evidence of a tumor with 1 or more EGFR activating mutations excluding exon 20 insertion
- •Disease progression confirmed by radiological assessment while receiving treatment with single agent EGFR-TKI (e.g., erlotinib, gefitinib, afatinib, or dacomitinib) or EGFR-TKI in combination with other targeted therapy (e.g. bevacizumab, immunotherapy)
- •Multiple lines of prior treatment are permitted and there is no specified order of treatment, but in the course of their treatment history, patients must have received and have radiologically documented disease progression following:
- •At least 1 line of prior treatment with a single-agent EGFR-TKI (e.g., erlotinib, gefitinib, afatinib, or dacomitinib)
- •If EGFR-TKI is a component of the most recent treatment line, the washout period for the EGFR-TKI is a minimum of 3 days before the start of study drug treatment
- •A platinum-containing doublet chemotherapy (either progressed during therapy or completed at least 4 cycles without progression with subsequent progression after a treatment-free interval or after a maintenance treatment).
- •If cytotoxic chemotherapy is a component of the most recent treatment line, treatment with chemotherapy should have been completed at least 14 days prior to start of study treatment. When an EGFR-TKI is given in combination with platinum-containing doublet chemotherapy, treatment with the EGFR-TKI may continue until at least 3 days before start of treatment.
- •Have undergone a biopsy of either primary or metastatic tumor tissue within 60 days prior to start of treatment and have tissue sent to the central laboratory prior to randomization
- •Measureable disease according to RECIST Version 1.1
- •Life expectancy of at least 3 months
- •ECOG performance status of 0 to 1
- •Age ≥ 18 years (in certain territories, the minimum age requirement may be higher e.g., age ≥ 20 years in Japan and Taiwan, age ≥ 21 years in Singapore)
- •Patients should have recovered to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Grade ≤ 1 from any significant chemotherapy-related toxicities
- •Adequate hematological and biological function
- •Written consent on an Institutional Review Board (IRB)/Independent Ethics Committee (IEC)-approved ICF before any study specific evaluation
排除标准
- •Any of the following criteria will exclude patients from study participation:
- •Any other malignancy associated with a high mortality risk within the next 5 years and for which the patients may be (but not necessarily) currently receiving treatment
- •Patients with a history of malignancy that has been completely treated, with no evidence of that cancer currently, are permitted to enroll in the trial provided all chemotherapy was completed > 6 months prior and/or bone marrow transplant > 2 years prior
- •Known pre-existing interstitial lung disease
- •Tumor small cell transformation by local assessment, irrespective of presence of T790M+ component
- •Patients with leptomeningeal carcinomatosis are excluded. Other central nervous system (CNS) metastases are only permitted if treated, asymptomatic, and stable (not requiring steroids for at least 2 weeks prior to randomization and the patient is neurologically stable i.e. free from new symptoms of brain metastases)
- •Patients who are currently receiving treatment with any medications that have the potential to prolong the QT interval and that treatment cannot be either discontinued or switched to a different medication (known to have no effect on QT) before starting protocol-specified treatment (see http://crediblemeds.org/ for a list of QT-prolonging medications)
- •Prior treatment with rociletinib, or other drugs that target T790M+ mutant EGFR with sparing of WT-EGFR including but not limited to osimertinib, HM61713, and TAS-121
- •Any contraindications for therapy with pemetrexed, paclitaxel, gemcitabine or docetaxel unless a contraindication with respect to one of these drugs will not affect the use of any of the others as a comparator to rociletinib
- •Any of the following cardiac abnormalities or history:
- •Clinically significant abnormal 12-lead ECG, QT interval corrected using Fridericia's method (QTCF) > 450 msec
- •Inability to measure QT interval on ECG
- •Personal or family history of long QT syndrome
- •Implantable pacemaker or implantable cardioverter defibrillator
- •Resting bradycardia < 55 beats/min
- •Non-study related surgical procedures ≤ 7 days prior to randomization. In all cases, the patient must be sufficiently recovered and stable before treatment administration
- •Females who are pregnant or breastfeeding
- •Refusal to use adequate contraception for fertile patients (females and males) while on treatment and for 6 months after the last dose of study treatment (rociletinib and chemotherapy irrespective of single cytotoxic agent used)
- •Presence of any serious or unstable concomitant systemic disorder incompatible with the clinical study (e.g., substance abuse, uncontrolled intercurrent illness including uncontrolled diabetes, active infection, arterial thrombosis, and symptomatic pulmonary embolism)
- •Any other reason the investigator considers the patient should not participate in the study
- •Treatment with live vaccines initiated less than 4 weeks prior to randomization
研究组 & 干预措施
Rociletinib Monotherapy (500 mg BID)
Daily oral rociletinib at 500 mg BID with 8 oz (240 mL) of water and with a meal or within 30 minutes after a meal. Treatment with rociletinib is continuous and each cycle will comprise of 21 days.
干预措施: Rociletinib (Drug)
Rociletinib Monotherapy (625 mg BID)
Daily oral rociletinib at 625 mg BID with 8 oz (240 mL) of water and with a meal or within 30 minutes after a meal. Treatment with rociletinib is continuous and each cycle will comprise of 21 days.
干预措施: Rociletinib (Drug)
Pemetrexed or gemcitabine or paclitaxel or docetaxel
Pemetrexed
500 mg/m2 pemetrexed given intravenously on Day 1 of each 21-day cycle.
Gemcitabine
1250 mg/m2 gemcitabine given intravenously on Day 1 and 8 of each 21-day cycle.
Docetaxel
75 mg/m2 docetaxel (60 mg/m2 for patients residing in East-Asian territories) given intravenously on Day 1 of each 21-day cycle.
or 35 mg/m2 docetaxel given intravenously on a weekly basis as part of a continuous 21-day cycle; i.e. dosing will be on Days 1, 8, and 15 of each 21-day cycle.
Paclitaxel
80 mg/m2 paclitaxel given intravenously on a weekly basis as part of a continuous 21-day cycle; i.e. dosing will be on Days 1, 8, and 15 of each 21-day cycle.
干预措施: Pemetrexed or gemcitabine or paclitaxel or docetaxel (Drug)
结局指标
主要结局
Progression Free Survival (PFS) According to RECIST Version 1.1 as Determined by Investigator Review (invPFS)
时间窗: Cycle 1 Day 1 to End of Treatment, up to approximately 35 months. This Time Frame includes the cross-over period, however, participants who crossed over to rociletinib were not analyzed for PFS.
PFS was calculated as 1+ the number of days from the date of randomization to documented radiographic progression as determined by the investigator, or death due to any cause, whichever occurs first. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.The appearance of one or more new lesions is also considered progression.
次要结局
- Overall Survival (OS)(Cycle 1 Day 1 to date of death, assessed up to 3 years)
- Plasma PK for Patients Treated With Rociletinib Based on Sparse Sampling(Cycles 2 Day 1 to Cycle 7 Day 1, or approximately 6 months)
- Percentage of Participants With Confirmed Response(Cycle 1 Day 1 to End of Treatment, up to approximately 35 months. This Time Frame includes the cross-over period, however, participants who crossed over to rociletinib were not analyzed for best overall confirmed response.)
- Duration of Response (DOR) According to RECIST Version 1.1 as Determined by Investigator Assessment(Cycle 1 Day 1 to End of Treatment, up to approximately 35 months)