ARCHER1050: A Study of Dacomitinib vs. Gefitinib in 1st-Line Treatment Of Advanced NSCLC.

• ClinicalTrials.gov Identifier: NCT01774721
• Recruitment Status: Completed
• First Posted: January 24, 2013
• Results First Posted: October 26, 2018
• Last Update Posted: November 14, 2023
• Sponsor: Pfizer
• Information provided by (Responsible Party): Pfizer

Tracking Information

• First Submitted Date: January 21, 2013
• First Posted Date: January 24, 2013
• Results First Submitted Date: March 29, 2018
• Results First Posted Date: October 26, 2018
• Last Update Posted Date: November 14, 2023
• Actual Study Start Date: May 9, 2013
• Actual Primary Completion Date: July 29, 2016 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: July 6, 2021)

Progression Free Survival (PFS) Based on Independent Radiologic Central (IRC) Review [ Time Frame: 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.

Original Primary Outcome Measures (submitted: January 21, 2013)

Progression Free Survival per Independent Radiologic review [ Time Frame: 18 months after anticipated LSFV ]

The purpose of this trial is to determine if PF-00299804 (dacomitinib) can extend progression free survival vs. gefitinib in the first-line treatment in patients with locally advanced or metastatic non-small cell lung cancer with epidermal growth factor receptor (EGFR) activating mutation (s).

Current Secondary Outcome Measures (submitted: February 6, 2023)

• Overall Survival (OS) [ Time Frame: From randomization until death or last date known as alive, up to 45 months ]
  OS was defined as the time from randomization to the date of death for any cause. In the absence of confirmation of death, survival time was censored at the last date the participant was known to be alive. OS (month)=[death date or last known alive date - randomization date + 1]/30.4375.
• OS at 30 Months (OS30m) [ Time Frame: Up to 30 months from date of randomization ]
  OS30m was defined as the probability of a participant being alive at 30 months from date of randomization.
• Progression Free Survival (PFS) Based on Investigator Assessment [ Time Frame: 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 PD as determined by investigator assessment as per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria or death due to any cause, whichever occurred first. PD for target lesions: 20% increase in sum of diameters of target measurable lesions above smallest sum observed, with minimum absolute increase of 5 mm; for non-target lesions: unequivocal progression of pre-existing lesions. 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.
• Number of Participants With Best Overall Response (BOR) Based on IRC Review [ Time Frame: Day 28 of Cycle 1, Cycle 2 then every 8 weeks until disease progression (up to 48 months) ]
  BOR for CR/PR:>=1 objective status (OBS) of CR/PR documented before PD; SD:>=1 OBS of stable documented >=8 weeks (wks) post treatment & before PD, not qualifying as CR/PR; PD:OBS of PD within 12 wks treatment, not qualifying as CR/PR/SD; indeterminate:PD not documented within 12 wks post treatment & no other response category applies. RECIST v1.1, CR:disappearance of all target lesions (TLs), non TLs;any pathological lymph nodes (LN) must reduce in short axis to <10 mm; normalization of tumour marker level, for non TL all LN must be non-pathological in size (<10 mm short axis); PR:>=30% decrease in sum of diameters of TLs, referring baseline sum diameters. SD:neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, referring smallest sum diameters on study. PD:>=20% increase in sum of diameters of 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.
• Number of Participants With Best Overall Response (BOR) Based on Investigator Assessment [ Time Frame: Day 28 of Cycle 1, Cycle 2 then every 8 weeks until disease progression (up to 48 months) ]
  BOR for CR/PR:>=1 objective status (OBS) of CR/PR documented before PD; SD:>=1 OBS of stable documented >=8 weeks (wks) post treatment & before PD, not qualifying as CR/PR; PD:OBS of PD within 12 wks treatment, not qualifying as CR/PR/SD; indeterminate:PD not documented within 12 wks post treatment & no other response category applies. RECIST v1.1, CR:disappearance of all target lesions (TLs), non TLs;any pathological lymph nodes (LN) must reduce in short axis to <10 mm; normalization of tumour marker level, for non TL all LN must be non-pathological in size (<10 mm short axis); PR:>=30% decrease in sum of diameters of TLs, referring baseline sum diameters. SD:neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, referring smallest sum diameters on study. PD:>=20% increase in sum of diameters of 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.
• Duration of Response (DoR) [ Time Frame: 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) ]
  DoR was defined as time from first documentation of objective response(CR or PR, whichever occurred first)to date of PD/death from any cause, whichever occurred first. CR: disappearance of all target lesions (TLs), non TLs; any pathological lymph nodes (LN) must reduce in short axis to <10 mm; normalization of tumour marker level, for non TL all LN must be non-pathological in size (<10 mm short axis); PR:>=30% decrease in sum of diameters of TLs, referring baseline sum diameters. PD:>=20% increase in sum of diameters of 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. DoR was recorded based on IRC review and investigator's assessment and summarized for subgroup of participants with objective disease response.
• Objective Response Rate (ORR) Based on IRC Review [ Time Frame: Day 28 of Cycle 1, Cycle 2 then every 8 weeks until disease progression (up to 48 months) ]
  Percentage of participants with a BOR of either CR or PR based on IRC review recorded from the start of treatment until disease progression based on RECIST v1.1. CR: disappearance of all target lesions (TLs), non TLs; any pathological lymph nodes (LN) must reduce in short axis to <10 mm; normalization of tumour marker level, for non TL all LN must be non-pathological in size (<10 mm short axis); PR:>=30% decrease in sum of diameters of TLs, referring baseline sum diameters. PD:>=20% increase in sum of diameters of 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.
• Objective Response Rate (ORR) Based on Investigator Assessment [ Time Frame: Day 28 of Cycle 1, Cycle 2 then every 8 weeks until disease progression (up to 48 months) ]
  Percentage of participants with a BOR of either CR or PR based on investigator assessment recorded from the start of treatment until disease progression based on RECIST v1.1. CR: disappearance of all target lesions (TLs), non TLs; any pathological lymph nodes (LN) must reduce in short axis to <10 mm; normalization of tumour marker level, for non TL all LN must be non-pathological in size (<10 mm short axis); PR:>=30% decrease in sum of diameters of TLs, referring baseline sum diameters. PD:>=20% increase in sum of diameters of 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.
• Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: From randomization until death or last date known as alive, up to 91 months ]
  An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship.AEs included both serious and non- serious adverse events. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent AEs were events between first dose of study drug and up to 28-35 days after last dose that were absent before treatment or that worsened relative to pretreatment state.
• Number of Participants With Laboratory Test Abnormalities of Grade 3 or Higher Severity Based on NCI CTCAE Version 4.03: Biochemistry and Haematology [ Time Frame: From randomization until death or last date known as alive, up to 61 months ]
  Parameters included anaemia, activated partial thromboplastin time, haemoglobin, international normalized ratio, lymphocyte count, lymphopenia, neutrophils (absolute), platelets, prothrombin time and white blood cells. Biochemistry parameters included alanine aminotransferase (increased), alkaline phosphatase (increased), aspartate aminotransferase (increased), bilirubin (total), creatinine (increased), hypercalcaemia, hyperglycaemia, hyperkalaemia, hypermagnesaemia, hypernatraemia, hypoalbuminaemia, hypocalcaemia, hypoglycaemia, hypokalaemia, hypomagnesaemia, hyponatraemia. Test abnormalities were graded by AEs according to the Common Terminology Criteria for Adverse Events(NCI CTCAE) version 4.03 as Grade 1=mild; Grade 2=moderate; Grade 3=severe; Grade 4=life-threatening; Grade 5=death related to AE. Only categories with at least 1 participant with abnormality are reported in this outcome measure.
• Number of Participants With Laboratory Test Abnormalities: Urinalysis [ Time Frame: From randomization until death or last date known as alive, up to 61 months ]
  Urinalysis parameter included urine protein, urine blood/haemoglobin, urine glucose and urine sediment. Test abnormalities was defined as deviation from normal range (higher or lower). Normal range of 24-hour urine protein test: less than 150 mg of protein per day, urine glucose: 0 to 0.8 mmol/L (millimole per liter), urine protein: 0 to 20 mg/dL (milligrams per deciliter). Urine blood/haemoglobin abnormality was defined as presence and absence of blood/haemoglobin in urine of participants. Urine sediment abnormality was defined as the presence of any bacteria, casts, crystals, and epithelial cells. Only categories with at least 1 participant with abnormality are reported in this outcome measure.
• Number of Participants With Clinically Significant Abnormalities in Vital Signs [ Time Frame: From randomization until death or last date known as alive, up to 61 months ]
  Criteria for vital signs abnormalities: postbaseline pulse rate less than (<) 50 beats per minute (bpm) or greater than (>)130 bpm and maximum increase from baseline in pulse rate >=30 bpm and maximum decrease from baseline in pulse rate <=30 bpm. Systolic blood pressure (BP) of maximum increase from baseline (MIB) >=40 millimeters of mercury (mmHg), maximum decrease from baseline (MDB) in systolic blood pressure =<60 mmHg. Diastolic blood pressure of MIB >=20 mmHg and MDB in diastolic blood pressure >-40 and =<-20 mm Hg. And MDB in diastolic BP<=-40 mmHg. Only categories with at least 1 participant with abnormality are reported in this outcome measure.
• Number of Participants With Clinically Significant Abnormality in Electrocardiogram (ECG) [ Time Frame: From randomization until death or last date known as alive, up to 61 months ]
  ECG parameters included corrected QT interval using Bazett's formula (QTcB) and corrected QT interval using Fridericia's formula (QTcF). ECG criteria for abnormality: absolute value 450 - <480 msec, 480 - <500 msec, >=500msec. The number of participants with potentially clinically significant ECG findings at any visit were reported.
• Number of Participants With Maximum Relative Decrease From Baseline >20% in Left Ventricular Ejection Fraction (LVEF) [ Time Frame: From baseline up to 7 days of Cycle 4 (up to 91 days) ]
  An ejection fraction (EF) was the volumetric fraction of blood ejected from a ventricle of the heart with each heartbeat; it was a measure of the pumping efficiency of the heart. The EF of the left heart, known as the left ventricular ejection fraction, was a measure of the efficiency of pumping into the body's systemic circulation.
• Health Related Quality of Life (HRQOL): Time to Deterioration (TTD) in Pain, Dyspnea, Fatigue or Cough [ Time Frame: Baseline until the end of treatment (up to 48 months) ]
  HRQOL was measured by standardized questionnaires (European Organization for Research and Treatment of Cancer (EORTC)) quality of life questionnaires (OLQ-C30) and its lung cancer module (QLQ-LC13). TTD in pain (chest, arm/shoulder), dyspnea, fatigue or cough was defined as time between baseline and first occurrence of increase in score of 10 points or greater from baseline in any of these 4 symptoms for at least two consecutive cycles. For those who had not shown deterioration, the data was censored at the last date when the participants completed an assessment for pain, dyspnea, fatigue or cough.
• Overall Mean Scores of Euro Quality of Life-5 Dimension Visual Analog Scale (EQ-5D VAS) [ Time Frame: From Cycle 1 Day 1 up to 48 months ]
  The Euro Quality of Life-5 dimension (EQ-5D) is a brief self-administered, validated reliable generic health status instrument. EQ-5D general health status can also be measured by a visual analog scale (EQ-5D VAS). EQ-5D VAS measures the participant's self-rated health status on a scale from 0 (worst imaginable health state) to 100 (best imaginable health state).
• Maximum Observed Plasma Concentration (Cmax) of Dacomitinib and Its Metabolite PF-05199265 [ Time Frame: Pre-dose and 2, 4, 6, 8, and 24 hours post-dose on Cycle 2 Day 1 (Day 29) ]
  Cmax was defined as maximum observed plasma concentration and can be observed directly from data.
• Time to Reach Maximum Observed Plasma Concentration (Tmax) of Dacomitinib and Its Metabolite PF-05199265 [ Time Frame: 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) ]
  Tmax was defined as time to first occurrence of Cmax and can be observed directly from data as time of first occurrence.
• Area Under the Plasma Concentration-Time Curve From Time Zero (0) to End of Dosing Interval (AUCtau) of Dacomitinib and Its Metabolite PF-05199265 [ Time Frame: Pre-dose and 2, 4, 6, 8, and 24 hours post-dose on Cycle 2 Day 1 (Day 29) ]
  AUCtau was defined as area under the plasma concentration-time curve over dosing interval tau and was determined by Linear/Log trapezoidal method.
• Averaged Plasma Concentration at Steady State (Cavg) of Dacomitinib and Its Metabolite PF-05199265 [ Time Frame: Pre-dose and 2, 4, 6, 8, and 24 hours post-dose on Cycle 2 Day 1 (Day 29) ]
  Cavg was defined as averaged plasma concentration at steady state, and was calculated as AUCtau/tau.
• Minimum Observed Plasma Concentration (Cmin) of Dacomitinib and Its Metabolite PF-05199265 [ Time Frame: Pre-dose and 2, 4, 6, 8, and 24 hours post-dose on Cycle 2 Day 1 (Day 29) ]
  Cmin was defined as minimum observed plasma concentration and can be observed directly from data.
• Fluctuation Coefficient Between Trough and Peak Plasma Concentration (DF) of Dacomitinib and Its Metabolite PF-05199265 [ Time Frame: 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 was determined as Cmax-Ctrough divided by Cavg, where Cmax was the maximum observed concentration within the dosing interval, Ctrough was the observed concentration prior to dose administration and Cavg was averaged plasma concentration at steady state.
• Apparent Clearance (CL) of Dacomitinib [ Time Frame: Pre-dose and 2, 4, 6, 8, and 24 hours post-dose on Cycle 2 Day 1 (Day 29) ]
  Drug clearance was a quantitative measure of the rate at which a drug substance was removed from the blood (rate at which a drug is metabolized or eliminated by normal biological processes).
• Pre-dose Plasma Concentrations (Ctrough) of Dacomitinib and Its Metabolite PF-05199265 [ Time Frame: Pre-dose on Day 1 of Cycle 2, 3, 4, 5 and 6 ]
  Trough plasma concentration was defined as the measured concentration at the end of a dosing interval at steady state (taken directly before next administration).

Original Secondary Outcome Measures (submitted: January 21, 2013)

• Overall Survival (OS) and OS at 30 months (OS30m); [ Time Frame: 30 months after LSFV ]
• PFS by investigator assessment [ Time Frame: 18 months after LSFV ]
• Best Overall Response (BOR) [ Time Frame: 18 months after LSFV ]
• Duration of Response (DR) [ Time Frame: 18 months after LSFV ]
• Overall safety profile [ Time Frame: 18 months after LSFV ]
• Patient Reported Outcomes (PRO) of health related quality of life (HRQOL) [ Time Frame: 18 months after LSFV ]
• Patient Reported Outcomes (PRO) by EQ-5D [ Time Frame: 18 months after LSFV ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: ARCHER1050: A Study of Dacomitinib vs. Gefitinib in 1st-Line Treatment Of Advanced NSCLC.
• Official Title: 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)
• Brief Summary: 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.
• Detailed Description: 452 patients were randomized in a 1:1 ratio between dacomitinib (PF-00299804 ) vs. gefitinib.
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Non-small Cell Lung Cancer With EGFR-Activating Mutations

Intervention

• Drug: Dacomitinib (PF-00299804)
  Dacomitinib (PF-00299804) 45 mg tablets, continuous oral daily dosing.
  Other Name: Dacomitinib
• Drug: Gefitinib
  Gefitinib 250 mg tablets, continuous oral daily dosing.
  Other Name: Iressa

Study Arms

• Experimental: Dacomitinib (PF-00299804)
  Dacomitinib (PF-00299804) is provided as 45 mg tablets, continuous oral daily dosing.
  Intervention: Drug: Dacomitinib (PF-00299804)
• Active Comparator: gefitinib
  Gefitinib is provided as 250 mg tablets, continuous oral daily dosing.
  Intervention: Drug: Gefitinib

Publications *

• Li J, Nickens D, Wilner K, Tan W. Evaluation of the Effect of Proton Pump Inhibitors on the Efficacy of Dacomitinib and Gefitinib in Patients with Advanced Non-Small Cell Lung Cancer and EGFR-Activating Mutations. Oncol Ther. 2021 Dec;9(2):525-539. doi: 10.1007/s40487-021-00156-2. Epub 2021 Jun 13.
• Cheng Y, Mok TS, Zhou X, Lu S, Zhou Q, Zhou J, Du Y, Yu P, Liu X, Hu C, Lu Y, Zhang Y, Lee KH, Nakagawa K, Linke R, Wong CH, Tang Y, Zhu F, Wilner KD, Wu YL. Safety and efficacy of first-line dacomitinib in Asian patients with EGFR mutation-positive non-small cell lung cancer: Results from a randomized, open-label, phase 3 trial (ARCHER 1050). Lung Cancer. 2021 Apr;154:176-185. doi: 10.1016/j.lungcan.2021.02.025. Epub 2021 Feb 23.
• Mok TS, Cheng Y, Zhou X, Lee KH, Nakagawa K, Niho S, Chawla A, Rosell R, Corral J, Migliorino MR, Pluzanski A, Noonan K, Tang Y, Pastel M, Wilner KD, Wu YL. Updated Overall Survival in a Randomized Study Comparing Dacomitinib with Gefitinib as First-Line Treatment in Patients with Advanced Non-Small-Cell Lung Cancer and EGFR-Activating Mutations. Drugs. 2021 Feb;81(2):257-266. doi: 10.1007/s40265-020-01441-6.
• Corral J, Mok TS, Nakagawa K, Rosell R, Lee KH, Migliorino MR, Pluzanski A, Linke R, Devgan G, Tan W, Quinn S, Wang T, Wu YL. Effects of dose modifications on the safety and efficacy of dacomitinib for EGFR mutation-positive non-small-cell lung cancer. Future Oncol. 2019 Aug;15(24):2795-2805. doi: 10.2217/fon-2019-0299. Epub 2019 Jul 17.
• Nagano T, Tachihara M, Nishimura Y. Dacomitinib, a second-generation irreversible epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) to treat non-small cell lung cancer. Drugs Today (Barc). 2019 Apr;55(4):231-236. doi: 10.1358/dot.2019.55.4.2965337.
• Mok TS, Cheng Y, Zhou X, Lee KH, Nakagawa K, Niho S, Lee M, Linke R, Rosell R, Corral J, Migliorino MR, Pluzanski A, Sbar EI, Wang T, White JL, Wu YL. Improvement in Overall Survival in a Randomized Study That Compared Dacomitinib With Gefitinib in Patients With Advanced Non-Small-Cell Lung Cancer and EGFR-Activating Mutations. J Clin Oncol. 2018 Aug 1;36(22):2244-2250. doi: 10.1200/JCO.2018.78.7994. Epub 2018 Jun 4. Erratum In: J Clin Oncol. 2020 Nov 1;38(31):3725.
• Wu YL, Cheng Y, Zhou X, Lee KH, Nakagawa K, Niho S, Tsuji F, Linke R, Rosell R, Corral J, Migliorino MR, Pluzanski A, Sbar EI, Wang T, White JL, Nadanaciva S, Sandin R, Mok TS. Dacomitinib versus gefitinib as first-line treatment for patients with EGFR-mutation-positive non-small-cell lung cancer (ARCHER 1050): a randomised, open-label, phase 3 trial. Lancet Oncol. 2017 Nov;18(11):1454-1466. doi: 10.1016/S1470-2045(17)30608-3. Epub 2017 Sep 25.
• Ramalingam SS, O'Byrne K, Boyer M, Mok T, Janne PA, Zhang H, Liang J, Taylor I, Sbar EI, Paz-Ares L. Dacomitinib versus erlotinib in patients with EGFR-mutated advanced nonsmall-cell lung cancer (NSCLC): pooled subset analyses from two randomized trials. Ann Oncol. 2016 Mar;27(3):423-9. doi: 10.1093/annonc/mdv593. Epub 2016 Jan 13. Erratum In: Ann Oncol. 2016 Jul;27(7):1363.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: March 29, 2018): 452
• Original Estimated Enrollment (submitted: January 21, 2013): 440
• Actual Study Completion Date: January 27, 2022
• Actual Primary Completion Date: July 29, 2016 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• 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 0-1.
• Radiologically measurable disease.

Exclusion Criteria:

• 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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 99 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: China, Hong Kong, Italy, Japan, Korea, Republic of, Poland, Spain

Administrative Information

• NCT Number: NCT01774721
• Other Study ID Numbers: A7471050; DP312804 ( Other Identifier: Pfizer )
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.
• URL: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests

• Current Responsible Party: Pfizer
• Original Responsible Party: SFJ Pharmaceuticals, Inc.
• Current Study Sponsor: Pfizer
• Original Study Sponsor: SFJ Pharmaceuticals, Inc.
• Collaborators: Not Provided

Investigators

• Study Director: Pfizer CT.gov Call Center; Pfizer

• PRS Account: Pfizer
• Verification Date: January 2023