Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Lung Neoplasms

Carcinoma, Non-Small-Cell Lung

Carcinoma

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

All Drugs and Chemicals

Antineoplastic Agents

Amino Acids

Mitogens

Gefitinib

Dacomitinib

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Tyrosine

Dacomitinib (PF-00299804) is provided as 45 mg tablets, continuous oral daily dosing.

Gefitinib is provided as 250 mg tablets, continuous oral daily dosing.

Dacomitinib (PF-00299804) 45 mg tablets, continuous oral daily dosing.

Dacomitinib (PF-00299804)

Gefitinib 250 mg tablets, continuous oral daily dosing.

Pfizer CT.gov Call Center

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.

452 patients were randomized in a 1:1 ratio between dacomitinib (PF-00299804 ) vs. gefitinib.

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

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)

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.

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.

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.

OS30m was defined as the probability of a participant being alive at 30 months from date of randomization.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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).

Cmax was defined as maximum observed plasma concentration and can be observed directly from data.

Tmax was defined as time to first occurrence of Cmax and can be observed directly from data as time of first occurrence.

AUCtau was defined as area under the plasma concentration-time curve over dosing interval tau and was determined by Linear/Log trapezoidal method.

Cavg was defined as averaged plasma concentration at steady state, and was calculated as AUCtau/tau.

Cmin was defined as minimum observed plasma concentration and can be observed directly from data.

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.

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).

Trough plasma concentration was defined as the measured concentration at the end of a dosing interval at steady state (taken directly before next administration).

Pfizer

The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Safety analysis set included all participants who received at least 1 dose of study medication, with treatment assignments designated according to actual study treatment received.

Participants received 45 mg of dacomitinib tablets orally once daily in each treatment cycle of 28 days, up to a maximum of 48 months until disease progression, intolerable toxicities, withdrawal, death, or investigator decision dictated by protocol compliance, whichever occurred first.

Participants received 250 mg of gefitinib tablets orally once daily in each treatment cycle of 28 days, for maximum of 48 months until disease progression, intolerable toxicities, withdrawal, death, or investigator decision dictated by protocol compliance, whichever occurred first.

DCO was the protocol-defined cutoff at 48 months from first dosing of the last enrolled participant (13 May 2019). At the DCO, 11 participants were ongoing in the dacomitinib arm and continued study treatment until disease progression, intolerable toxicities, withdrawal, death, or study terminated by sponsor, whichever occurred first. The 11 participants were analyzed for adverse events after LPLV on 27 Jan 2022.

Dacomitinib (Ongoing at DCO)

Total

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

ITT Population included all participants who were randomized, with study treatment assignment designated according to initial randomization, regardless of whether participants received study treatment or received a different treatment from that to which they were randomized.

Pfizer ClinicalTrials.gov Call Center

Intent to treat (ITT) Population included all randomized participants, with study treatment assignment designated according to initial randomization, regardless of whether participants received study treatment or a different treatment from that to which they were randomized.

Progression Free Survival (PFS) Based on Independent Radiologic Central (IRC) Review

ITT Population included all randomized participants, with study treatment assignment designated according to initial randomization, regardless of whether participants received study treatment or a different treatment from that to which they were randomized.

Overall Survival (OS)

OS at 30 Months (OS30m)

Participants received 250 mg of gefitinib tablets orally once daily in each treatment cycle of 28 days, up to a maximum of 48 months until disease progression, intolerable toxicities, withdrawal, death, or investigator decision dictated by protocol compliance, whichever occurred first.

Progression Free Survival (PFS) Based on Investigator Assessment

Complete response

Partial response

Stable disease

Progressive disease

Indeterminate

Number of Participants With Best Overall Response (BOR) Based on IRC Review

Number of Participants With Best Overall Response (BOR) Based on Investigator Assessment

Comparison of dacomitinib vs gefitinib based on IRC review

Comparison of dacomitinib vs gefitinib based on Investigator assessment

DoR: IRC review

DoR: Investigator assessment

Duration of Response (DoR)

Objective Response Rate (ORR) Based on IRC Review

Objective Response Rate (ORR) Based on Investigator Assessment

TEAEs

SAEs

Safety analysis set included all participants who received at least 1 dose of study medication, with treatment assignments designated according to actual study treatment received.

Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)

Anaemia (Grade 3)

Haemoglobin increased(Grade 3)

Lymphopenia (Grade 3)

Neutrophil count (absolute) (Grade 3)

WBC count (Grade 3)

Alanine aminotransferase increased (Grade 3)

Alanine aminotransferase increased (Grade 4)

Aspartate aminotransferase increased (Grade 3)

Aspartate aminotransferase increased (Grade 4)

Alkaline phosphatase increased (Grade 3)

Bilirubin increased (total) (Grade 3)

Creatinine increased (Grade 3)

Hypercalcemia (Grade 3)

Hyperglycemia (Grade 3)

Hyperkalemia (Grade 3)

Hyperkalemia (Grade 4)

Hypermagnesemia (Grade 3)

Hypocalcemia (Grade 3)

Hypoglycemia (Grade 3)

Hypoglycemia (Grade 4)

Hypokalemia (Grade 3)

Hypokalemia (Grade 4)

Hypomagnesemia (Grade 3)

Hyponatremia (Grade 3)

Hyponatremia (Grade 4)

Number of Participants With Laboratory Test Abnormalities of Grade 3 or Higher Severity Based on NCI CTCAE Version 4.03: Biochemistry and Haematology

High Urine Protein

Low Urine Glucose

High Urine Blood/Haemoglobin

Number of Participants With Laboratory Test Abnormalities: Urinalysis

MIB in systolic BP >=40 mmHg

MDB in systolic BP <=-60 mmHg

MIB in diastolic BP >=20 mmHg

MDB in diastolic BP >-40 and <=-20mmHg

MDB in diastolic BP <=-40 mmHg

Maximum post baseline pulse rate >130 bpm

Minimum post baseline pulse rate <50 bpm

MIB in pulse rate >=30 bpm

MDB in pulse rate <=-30 bpm

MIB in body weight >=10%

MDB in body weight <=-10%

Number of Participants With Clinically Significant Abnormalities in Vital Signs

QTcF Criteria: 450-<480

QTcB Criteria: 450-<480

QTcB Criteria: 480-<500

Safety analysis set included all participants who received at least 1 dose of study medication, with treatment assignments designated according to actual study treatment received. Here, "N" (number of participants analyzed) signifies participants who were evaluable for this specified outcome measure.

Number of Participants With Clinically Significant Abnormality in Electrocardiogram (ECG)

Safety analysis set included all participants who received at least 1 dose of study medication, with treatment assignments designated according to actual study treatment received. Here "N" signifies number of participants who were evaluable for this specified outcome measure.

Number of Participants With Maximum Relative Decrease From Baseline >20% in Left Ventricular Ejection Fraction (LVEF)

Patient reported outcomes (PRO) analysis set included all enrolled participants, who started treatment and completed a baseline PRO assessments and at least one post-baseline PRO assessment after the first dose.

Health Related Quality of Life (HRQOL): Time to Deterioration (TTD) in Pain, Dyspnea, Fatigue or Cough

PRO analysis set included all enrolled participants, who started treatment and completed a baseline PRO assessments and at least one post-baseline PRO assessment after the first dose. Here "N" signifies number of participants who were evaluable for this specified outcome measure.

Overall Mean Scores of Euro Quality of Life-5 Dimension Visual Analog Scale (EQ-5D VAS)

PF-05199265

Pharmacokinetic (PK) analysis set included all participants who were treated with dacomitinib with at least 1 measured plasma concentration and were dose-compliant (who received 45 mg dacomitinib daily without interruptions/dose reductions for at least 14 days prior to day of data collection). This outcome measure was planned to be analyzed in Chinese subgroup only.

Maximum Observed Plasma Concentration (Cmax) of Dacomitinib and Its Metabolite PF-05199265

PK analysis set included all participants who were treated with dacomitinib with at least 1 measured plasma concentration and were dose-compliant (who received 45 mg dacomitinib daily without interruptions/dose reductions for at least 14 days prior to day of data collection). This outcome measure was planned to be analyzed in Chinese subgroup only.

Time to Reach Maximum Observed Plasma Concentration (Tmax) of Dacomitinib and Its Metabolite PF-05199265

Area Under the Plasma Concentration-Time Curve From Time Zero (0) to End of Dosing Interval (AUCtau) of Dacomitinib and Its Metabolite PF-05199265

Averaged Plasma Concentration at Steady State (Cavg) of Dacomitinib and Its Metabolite PF-05199265

Minimum Observed Plasma Concentration (Cmin) of Dacomitinib and Its Metabolite PF-05199265

Fluctuation Coefficient Between Trough and Peak Plasma Concentration (DF) of Dacomitinib and Its Metabolite PF-05199265

Apparent Clearance (CL) of Dacomitinib

Cycle 2 Day 1: Dacomitinib

Cycle 3 Day 1: Dacomitinib

Cycle 4 Day 1: Dacomitinib

Cycle 5 Day 1: Dacomitinib

Cycle 6 Day 1: Dacomitinib

Cycle 2 Day 1: PF-05199265

Cycle 3 Day 1: PF-05199265

Cycle 4 Day 1: PF-05199265

Cycle 5 Day 1: PF-05199265

Cycle 6 Day 1: PF-05199265

PK analysis set included all participants who were treated with dacomitinib with at least one measured plasma concentration and were dose-compliant. Dose-compliant participants were those who received 45 mg dacomitinib daily without interruptions or dose reductions for at least 14 days prior to the day of data collection. Here, 'Number Analyzed' = participants evaluable for this outcome measure at specified time points.

Spots Global Cancer Trial Database for ARCHER1050: A Study of Dacomitinib vs. Gefitinib in 1st-Line Treatment Of Advanced NSCLC.

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