ARCHER 1050: A RANDOMIZED, OPEN-LABEL, PHASE 3, EFFICACY AND SAFETY STUDY OF DACOMITINIB (PF-00299804) VERSUS GEFITINIB FOR THE FIRST LINE TREATMENT OF LOCALLY ADVANCED OR METASTATIC NON-SMALL CELL LUNG CANCER IN SUBJECTS WITH EPIDERMAL GROWTH FACTOR RECEPTOR (EGFR) ACTIVATING MUTATION(S)
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- Pfizer
- 入组人数
- 452
- 主要终点
- Progression Free Survival (PFS) Based on Independent Radiologic Central (IRC) Review
研究概览
简要总结
This is a multinational, multicenter, randomized, open-label, Phase 3 study comparing the efficacy and safety of treatment with dacomitinib (PF-00299804) to treatment with gefitinib in patients with locally advanced or metastatic non-small cell lung cancer, with epidermal growth factor receptor EGFR-activating mutation (s). Analyses of primary objective (Progression Free Survival) will be done as defined in the protocol.
详细描述
452 patients were randomized in a 1:1 ratio between dacomitinib (PF-00299804 ) vs. gefitinib.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 99 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Evidence of histo or cytopathology confirmed, advanced NSCLC (with known histology) with the presence of EGFR-activating mutation (exon 19 deletion or the L858R mutation in exon 21).
- •It is acceptable for subjects with the presence of the exon 20 T790M mutation together with either EGFR-activating mutation (exon 19 deletion or the L858R mutation in exon 21) to be included in this study
- •No prior treatment with systemic therapy for locally advanced or metastatic NSCLC. Minimum of 12 months disease free interval between completion of neoadjuvant/adjuvant systemic therapy and recurrence of NSCLC
- •Adequate tissue sample must be available for central analyses.
- •Adequate renal, hematologic, liver function.
- •ECOG PS of 0-
- •Radiologically measurable disease.
排除标准
- •Any evidence of mixed histology that includes elements of small cell or carcinoid lung cancer.
- •Any other mutation other than exon 19 deletion or L858R in exon 21, with or without the presence of the exon 20 T790M mutation.
- •Any history of brain metastases or leptomeningeal metastases.
- •Any previous anti-cancer systemic treatment of early, locally advanced, or metastatic NSCLC.
- •Any surgery(not including minor procedures such as lymph node biopsy), palliative radiotherapy or pleurodesis within 2 weeks of baseline assessments
- •Any clinically significant gastrointestinal abnormalities that may impair intake, transit or absorption of the study drug.
- •Current enrollment in another therapeutic clinical study.
- •History of, or currently suspected, diffuse non-infectious pneumonitis or interstitial lung disease
- •Uncontrolled medical disorders.
- •Prior malignancy and concurrent malignancy except for non melanoma skin cancer or in-situ cervical cancer with no evidence of active disease.
- •Use of narrow therapeutic index drugs that are CYP2D6 substrates from screening to randomization.
研究组 & 干预措施
Dacomitinib (PF-00299804)
Dacomitinib (PF-00299804) is provided as 45 mg tablets, continuous oral daily dosing.
干预措施: Dacomitinib (PF-00299804) (Drug)
gefitinib
Gefitinib is provided as 250 mg tablets, continuous oral daily dosing.
干预措施: Gefitinib (Drug)
结局指标
主要结局
Progression Free Survival (PFS) Based on Independent Radiologic Central (IRC) Review
时间窗: Day 28 of Cycle 1, Cycle 2 then every 8 weeks until disease progression or death due to any cause, whichever occurred first (up to 48 months)
PFS: time from randomization to date of progression of disease (PD) as determined by IRC review as per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria or death due to any cause, whichever occurred first. PD: \>=20% increase in sum of diameters of target lesions (TLs), referring smallest sum on study, sum must be an absolute increase of \>=5 mm, appearance of \>=1 new lesions; unequivocal progression of existing non TLs. Overall tumor burden increased sufficiently to merit discontinuation of therapy. In presence of stable disease (did not achieve partial response, complete response or PD) or partial response (\>=30% decrease under baseline of sum of diameters of all target measurable lesions, short diameter used in the sum for target nodes, longest diameter used in sum for all other target lesions) in target disease; for new lesions: appearance of any new unequivocal malignant lesion indicated PD.
次要结局
- Overall Survival (OS)(From randomization until death or last date known as alive, up to 45 months)
- OS at 30 Months (OS30m)(Up to 30 months from date of randomization)
- Progression Free Survival (PFS) Based on Investigator Assessment(Day 28 of Cycle 1, Cycle 2 then every 8 weeks until disease progression or death due to any cause, whichever occurred first (up to 48 months))
- Number of Participants With Best Overall Response (BOR) Based on IRC Review(Day 28 of Cycle 1, Cycle 2 then every 8 weeks until disease progression (up to 48 months))
- Number of Participants With Laboratory Test Abnormalities: Urinalysis(From randomization until death or last date known as alive, up to 61 months)
- Number of Participants With Best Overall Response (BOR) Based on Investigator Assessment(Day 28 of Cycle 1, Cycle 2 then every 8 weeks until disease progression (up to 48 months))
- Duration of Response (DoR)(Day 28 of Cycle 1, Cycle 2 then every 8 weeks until disease progression or death due to any cause, whichever occurred first (up to 48 months))
- Objective Response Rate (ORR) Based on IRC Review(Day 28 of Cycle 1, Cycle 2 then every 8 weeks until disease progression (up to 48 months))
- Objective Response Rate (ORR) Based on Investigator Assessment(Day 28 of Cycle 1, Cycle 2 then every 8 weeks until disease progression (up to 48 months))
- Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)(From randomization until death or last date known as alive, up to 91 months)
- Number of Participants With Laboratory Test Abnormalities of Grade 3 or Higher Severity Based on NCI CTCAE Version 4.03: Biochemistry and Haematology(From randomization until death or last date known as alive, up to 61 months)
- Number of Participants With Maximum Relative Decrease From Baseline >20% in Left Ventricular Ejection Fraction (LVEF)(From baseline up to 7 days of Cycle 4 (up to 91 days))
- Minimum Observed Plasma Concentration (Cmin) of Dacomitinib and Its Metabolite PF-05199265(Pre-dose and 2, 4, 6, 8, and 24 hours post-dose on Cycle 2 Day 1 (Day 29))
- Fluctuation Coefficient Between Trough and Peak Plasma Concentration (DF) of Dacomitinib and Its Metabolite PF-05199265(Pre-dose and 2, 4, 6, 8, and 24 hours post-dose on Cycle 2 Day 1 (Day 29))
- Apparent Clearance (CL) of Dacomitinib(Pre-dose and 2, 4, 6, 8, and 24 hours post-dose on Cycle 2 Day 1 (Day 29))
- Pre-dose Plasma Concentrations (Ctrough) of Dacomitinib and Its Metabolite PF-05199265(Pre-dose on Day 1 of Cycle 2, 3, 4, 5 and 6)
- Number of Participants With Clinically Significant Abnormalities in Vital Signs(From randomization until death or last date known as alive, up to 61 months)
- Area Under the Plasma Concentration-Time Curve From Time Zero (0) to End of Dosing Interval (AUCtau) of Dacomitinib and Its Metabolite PF-05199265(Pre-dose and 2, 4, 6, 8, and 24 hours post-dose on Cycle 2 Day 1 (Day 29))
- Number of Participants With Clinically Significant Abnormality in Electrocardiogram (ECG)(From randomization until death or last date known as alive, up to 61 months)
- Time to Reach Maximum Observed Plasma Concentration (Tmax) of Dacomitinib and Its Metabolite PF-05199265(Pre-dose and 2, 4, 6, 8, and 24 hours post-dose (sample collection time points had window of +/- 10% of nominal time) on Cycle 2 Day 1 (Day 29))
- Averaged Plasma Concentration at Steady State (Cavg) of Dacomitinib and Its Metabolite PF-05199265(Pre-dose and 2, 4, 6, 8, and 24 hours post-dose on Cycle 2 Day 1 (Day 29))
- Health Related Quality of Life (HRQOL): Time to Deterioration (TTD) in Pain, Dyspnea, Fatigue or Cough(Baseline until the end of treatment (up to 48 months))
- Overall Mean Scores of Euro Quality of Life-5 Dimension Visual Analog Scale (EQ-5D VAS)(From Cycle 1 Day 1 up to 48 months)
- Maximum Observed Plasma Concentration (Cmax) of Dacomitinib and Its Metabolite PF-05199265(Pre-dose and 2, 4, 6, 8, and 24 hours post-dose on Cycle 2 Day 1 (Day 29))