ARCHER 1009 : A Study Of Dacomitinib (PF-00299804) Vs. Erlotinib In The Treatment Of Advanced Non-Small Cell Lung Cancer

Study Overview
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Brief Summary
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This is a multinational, multicenter, randomized,double-blinded, Phase 3 study comparing the efficacy and safety of treatment with PF-00299804 to treatment with erlotinib in patients with advanced non-small cell lung cancer, previously treated with at least one prior regimen. Analyses of primary objective (Progression Free Survival) will be done in two co-primary populations as defined in the protocol.

Official Title
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Archer 1009:a Randomized, Double Blind Phase 3 Efficacy And Safety Study Of Pf-00299804 (Dacomitinib) Versus Erlotinib For The Treatment Of Advanced Non-small Cell Lung Cancer Following Progression After, Or Intolerance To, At Least One Prior Chemotherapy

Conditions
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Non-Small Cell Lung Cancer

Intervention / Treatment
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* Drug: Dacomitinib (PF-00299804)
* Drug: Active Comparator (erlotinib)
* Drug: Placebo erlotinib
* Drug: Placebo PF00299804


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Evidence of pathologically confirmed, advanced NSCLC (with known histology). Prior treatment with at least one and no more than two systemic therapy regimens (at least one must be standard chemotherapy for advanced NSCLC). Adequate tissue sample must be submitted prior to randomization for tumor biomarker analyses. Adequate renal, hematologic, liver function. ECOG PS of 0-2. Radiologically measurable disease. Exclusion Criteria: Small cell histology. Symptomatic brain mets or known leptomeningeal mets. Prior therapy with agent known or proposed to be active by action on EGFR tyrosine kinase or other HER family proteins. Uncontrolled medical disorders.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A<br>Blinded active PF-00299804 + blinded placebo comparator (erlotinib) | Drug: Dacomitinib (PF-00299804)<br>* Dacomitinib (PF-00299804) is provided as 45 mg tablets, continuous oral daily dosing<br>Drug: Placebo erlotinib<br>* placebo erlotinib, provided as 150 mg tablet, continuous oral daily dosing.<br>|
| Active Comparator: B<br>Blinded active comparator (erlotinib) + blinded placebo PF-00299804 | Drug: Active Comparator (erlotinib)<br>* Active comparator (erlotinib) provided as 150 mg tablet, continuous oral daily dosing<br>Drug: Placebo PF00299804<br>* placebo PF-00299804, provide as 45 mg tablet, continuous oral daily dosing<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-Free Survival (PFS) Per Independent Radiologic Review. | PFS was defined as the time from randomization to the date of disease progression as by Response Evaluation Criteria in Solid Tumor (RECIST) v1.1 per Independent Radiologic Review or death due to any cause, whichever occurred first. Objective progression was defined as a 20% increase in the sum of the diameters of target measurable lesions above the smallest sum observed (over baseline if no decrease in the sum is observed during therapy), with a minimum absolute increase of 5 mm or unequivocal progression of pre-existing non-target lesions, or the appearance of any new unequivocal malignant lesions. | From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, participants were followed up until progressive disease regardless of start of subsequent cancer therapy. | 
| Progression-Free Survival (PFS) Per Independent Radiologic Review in KRAS Wild-type (WT) Participants. | PFS was defined as the time from randomization to the date of disease progression as by RECIST v1.1 per Independent Radiologic Review or death due to any cause, whichever occurred first. Objective progression was defined as a 20% increase in the sum of the diameters of target measurable lesions above the smallest sum observed (over baseline if no decrease in the sum is observed during therapy), with a minimum absolute increase of 5 mm or unequivocal progression of pre-existing non-target lesions, or the appearance of any new unequivocal malignant lesions. Tumor tissue from participants' original diagnostic biopsies or recently obtained biopsies were analyzed to determine KRAS status. | From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, participants were followed up until progressive disease regardless of start of subsequent cancer therapy. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PFS Based on Investigator Review. | PFS was defined as the time from randomization to the date of disease progression as by RECIST v1.1 per Investigator's Review or death due to any cause, whichever occurred first. Objective progression was defined as a 20% increase in the sum of the diameters of target measurable lesions above the smallest sum observed (over baseline if no decrease in the sum is observed during therapy), with a minimum absolute increase of 5 mm or unequivocal progression of pre-existing non-target lesions, or the appearance of any new unequivocal malignant lesions. | From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, participants were followed up until progressive disease regardless of start of subsequent cancer therapy. | 
| PFS Based on Investigator Review in KRAS-WT Participants. | PFS was defined as the time from randomization to the date of disease progression as by RECIST v1.1 per Investigator's Review or death due to any cause, whichever occurred first. Objective progression was defined as a 20% increase in the sum of the diameters of target measurable lesions above the smallest sum observed (over baseline if no decrease in the sum is observed during therapy), with a minimum absolute increase of 5 mm or unequivocal progression of pre-existing non-target lesions, or the appearance of any new unequivocal malignant lesions. Tumor tissue from participants' original diagnostic biopsies or recently obtained biopsies were analyzed to determine KRAS status. | From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, participants were followed up until progressive disease regardless of start of subsequent cancer therapy. | 
| Overall Survival (OS). | 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 patient was known to be alive (ie, at their last known alive date from long term follow-up). | From date of randomization until the date of death from any cause or last date known to be alive, participants were followed up regardless of the reason for discontinuation from study treatment at intervals of no longer than every 2 months. | 
| OS in KRAS-WT Participants. | 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 patient was known to be alive (ie, at their last known alive date from long term follow-up). Tumor tissue from participants' original diagnostic biopsies or recently obtained biopsies were analyzed to determine KRAS status. | From date of randomization until the date of death from any cause or last date known to be alive, participants were followed up regardless of the reason for discontinuation from study treatment at intervals of no longer than every 2 months. | 
| Best Overall Response (BOR) Per Independent Radiologic Review. | The BOR was the best response per RECIST (version 1.1) criteria as assessed by independent assessment recorded from randomization until disease progression. Per RECIST version 1.1: Complete Response (CR): disappearance of all pre-existing lesions except nodal disease, with all nodal lesions decreased to normal size (short axis<10 mm) and no appearance of new unequivocal malignant lesions; Partial Response (PR): >=30% decrease from baseline sum of diameters of all target lesions with no unequivocal progression of pre-existing non-target lesions or appearance of new unequivocal malignant lesions; Progressive Disease (PD): >=20% increase in the sum of diameters of target lesions above the smallest sum observed, with a minimum absolute increase of 5 mm, or unequivocal progression of pre-existing non-target lesions or appearance of any new unequivocal malignant lesions. | From date of randomization until progression or initiation of new anti-cancer therapy or death. Participants were followed up until progressive disease regardless of start of subsequent cancer therapy. | 
| BOR Per Investigator Review. | The BOR was the best response per RECIST (version 1.1) criteria as assessed by investigator assessment recorded from randomization until disease progression. Per RECIST version 1.1: CR: disappearance of all pre-existing lesions except nodal disease, with all nodal lesions decreased to normal size (short axis<10 mm) and no appearance of new unequivocal malignant lesions; PR: >=30% decrease from baseline sum of diameters of all target lesions with no unequivocal progression of pre-existing non-target lesions or appearance of new unequivocal malignant lesions; PD: >=20% increase in the sum of diameters of target lesions above the smallest sum observed, with a minimum absolute increase of 5 mm, or unequivocal progression of pre-existing non-target lesions or appearance of any new unequivocal malignant lesions. | From date of randomization until progression or initiation of new anti-cancer therapy or death. Participants were followed up until progressive disease regardless of start of subsequent cancer therapy. | 
| Duration of Response (DR) Based on Independent Radiologic Review. | DR was defined as the time from first documentation of response assessed by independent review (CR or PR whichever occurred first) to date of progression or death due to any cause, whichever occurs first. Per RECIST version 1.1: CR: disappearance of all pre-existing lesions except nodal disease, with all nodal lesions decreased to normal size (short axis<10 mm) and no appearance of new unequivocal malignant lesions; PR: >=30% decrease from baseline sum of diameters of all target lesions with no unequivocal progression of pre-existing non-target lesions or appearance of new unequivocal malignant lesions; PD: >=20% increase in the sum of diameters of target lesions above the smallest sum observed, with a minimum absolute increase of 5 mm, or unequivocal progression of pre-existing non-target lesions or appearance of any new unequivocal malignant lesions. | From date of randomization until progression or death due to any cause. Participants were followed up until progressive disease regardless of start of subsequent cancer therapy. | 
| DR Based on Investigator Review. | DR was defined as the time from first documentation of response assessed by investigator review (CR or PR whichever occurred first) to date of progression or death due to any cause, whichever occurs first. Per RECIST version 1.1: CR: disappearance of all pre-existing lesions except nodal disease, with all nodal lesions decreased to normal size (short axis<10 mm) and no appearance of new unequivocal malignant lesions; PR: >=30% decrease from baseline sum of diameters of all target lesions with no unequivocal progression of pre-existing non-target lesions or appearance of new unequivocal malignant lesions; PD: >=20% increase in the sum of diameters of target lesions above the smallest sum observed, with a minimum absolute increase of 5 mm, or unequivocal progression of pre-existing non-target lesions or appearance of any new unequivocal malignant lesions. | From date of randomization until progression or death due to any cause. Participants were followed up until progressive disease regardless of start of subsequent cancer therapy. | 
| Trough Concentrations (Ctrough) of Dacomitinib. | Mean Ctrough values of dacomitinib observed from Cycle 2 through 5, Day 1 for dose compliant participants. | Baseline up to Cycle 5 Day 1 | 
| Trough Concentrations (Ctrough) of PF-05199265. | Mean Ctrough values of PF-05199265 observed from Cycle 2 through 5, Day 1 for dose compliant participants. | Baseline up to Cycle 5 Day 1 | 
| Time to Deterioration (TTD) in Pain, Dyspnea, Fatigue or Cough Patient Reported Disease Symptoms. | TTD defined as the time from first dose (baseline) to the first time a patient's score in pain, dyspnea, fatigue or cough from the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (QLQ-LC13) increased by ≥10 points. A ≥10 point increase in score had to be maintained for ≥2 consecutive cycles for the symptom to be considered deteriorated. Participants were censored at the last time when they completed an assessment for pain, dyspnea, fatigue or cough if they had not deteriorated. A 10 point or higher change in the score is perceived by participants as clinically significant. | Data taken from Cycle 1 day 1 to the end of treatment or withdrawal. | 
| Mean and Difference in Mean in Functioning and Global Quality of Life (QOL) as Assessed by the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC-QLQ-C30) | EORTC QLQ-C30: included functional scales (physical, role, cognitive, emotional, and social), global health status, symptom scales (fatigue, pain, nausea/vomiting) and single items (dyspnoea, appetite loss, insomnia, constipation/diarrhea and financial difficulties). Scores ranged from 0-100 where a higher score indicated a better level of quality of life. Overall scores present the mean score for that scale from all time-point data. | Data taken from Cycle 1 day 1 to the end of treatment or withdrawal, averaged (mean) to provide overall scores. | 
| Mean and Difference in Mean in QLQ-C30 Symptoms as Assessed by the EORTC-QLQ-C30. | EORTC QLQ-C30: included functional scales (physical, role, cognitive, emotional, and social), global health status, symptom scales (fatigue, pain, nausea/vomiting) and single items (dyspnoea, appetite loss, insomnia, constipation/diarrhea and financial difficulties). Scores ranged from 0-100 where a higher score indicated a greater degree of symptoms/problems. Overall scores present the mean score for that scale from all time-point data. | Data taken from Cycle 1 day 1 to the end of treatment or withdrawal, averaged (mean) to provide overall scores. | 
| Mean and Difference in Mean in Lung Cancer Symptom Scores as Assessed by the EORTC QLQ- LC13. | The QLQ-LC13 included questions specific to the disease associated symptoms (dyspnea, cough, haemoptysis, and site specific pain), treatment-related symptoms (sore mouth, dysphagia, neuropathy, and alopecia), and analgesic use of lung cancer patients. Scores range from 0-100 and a higher score indicates greater degree of symptoms/problems. Overall scores present the mean score for that scale from all time-point data. | Data taken from Cycle 1 day 1 to the end of treatment or withdrawal, averaged (mean) to provide overall scores. | 
| Mean and Difference in Mean of the EuroQoL-5 Dimensions (EQ-5D) Visual Analogue Scale (VAS) Score | The EQ-5D is a validated and reliable self-report preference-based measure developed by the EuroQoL Group to assess health-related quality of life. It consists of the EQ-5D descriptive system and a visual analogue scale-the EQ VAS. The EQ-5D descriptive system measures a participants' health state on 5 dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension has 3 levels, reflecting no health problems, moderate health problems, and extreme health problems. The EQ VAS records the respondent's self-rated health on a scale from 0 (worst imaginable health state) to 100 (best imaginable health state). | Data taken from Cycle 1 day 1 to the end of treatment or withdrawal, averaged (mean) to provide overall scores. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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comparative study of PF-00299804 and Erlotinib, Double-Blind Phase 3 trial of TKI