Clinical trial NCT01774721: 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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Non-small Cell Lung Cancer With EGFR-Activating Mutations
Keywords: first-line
locally advanced or metastatic
non-small cell lung cancer
epidermal growth factor receptor
EGFR
ARCHER
mutation
dacomitinib
PF-00299804
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2013-01-24
Enrollment: 452
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Progression Free Survival (PFS) Based on Independent Radiologic Central (IRC) Review
timeFrame: 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)
Secondary outcomes:
measure: Overall Survival (OS)
timeFrame: From randomization until death or last date known as alive, up to 45 months
measure: OS at 30 Months (OS30m)
timeFrame: Up to 30 months from date of randomization
measure: Progression Free Survival (PFS) Based on Investigator Assessment
timeFrame: 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)
measure: Number of Participants With Best Overall Response (BOR) Based on IRC Review
timeFrame: Day 28 of Cycle 1, Cycle 2 then every 8 weeks until disease progression (up to 48 months)
measure: Number of Participants With Best Overall Response (BOR) Based on Investigator Assessment
timeFrame: Day 28 of Cycle 1, Cycle 2 then every 8 weeks until disease progression (up to 48 months)
measure: Duration of Response (DoR)
timeFrame: 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)
measure: Objective Response Rate (ORR) Based on IRC Review
timeFrame: Day 28 of Cycle 1, Cycle 2 then every 8 weeks until disease progression (up to 48 months)
measure: Objective Response Rate (ORR) Based on Investigator Assessment
timeFrame: Day 28 of Cycle 1, Cycle 2 then every 8 weeks until disease progression (up to 48 months)
measure: Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: From randomization until death or last date known as alive, up to 91 months
measure: Number of Participants With Laboratory Test Abnormalities of Grade 3 or Higher Severity Based on NCI CTCAE Version 4.03: Biochemistry and Haematology
timeFrame: From randomization until death or last date known as alive, up to 61 months
measure: Number of Participants With Laboratory Test Abnormalities: Urinalysis
timeFrame: From randomization until death or last date known as alive, up to 61 months
measure: Number of Participants With Clinically Significant Abnormalities in Vital Signs
timeFrame: From randomization until death or last date known as alive, up to 61 months
measure: Number of Participants With Clinically Significant Abnormality in Electrocardiogram (ECG)
timeFrame: From randomization until death or last date known as alive, up to 61 months
measure: Number of Participants With Maximum Relative Decrease From Baseline >20% in Left Ventricular Ejection Fraction (LVEF)
timeFrame: From baseline up to 7 days of Cycle 4 (up to 91 days)
measure: Health Related Quality of Life (HRQOL): Time to Deterioration (TTD) in Pain, Dyspnea, Fatigue or Cough
timeFrame: Baseline until the end of treatment (up to 48 months)
measure: Overall Mean Scores of Euro Quality of Life-5 Dimension Visual Analog Scale (EQ-5D VAS)
timeFrame: From Cycle 1 Day 1 up to 48 months
measure: Maximum Observed Plasma Concentration (Cmax) of Dacomitinib and Its Metabolite PF-05199265
timeFrame: Pre-dose and 2, 4, 6, 8, and 24 hours post-dose on Cycle 2 Day 1 (Day 29)
measure: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Dacomitinib and Its Metabolite PF-05199265
timeFrame: 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)
measure: Area Under the Plasma Concentration-Time Curve From Time Zero (0) to End of Dosing Interval (AUCtau) of Dacomitinib and Its Metabolite PF-05199265
timeFrame: Pre-dose and 2, 4, 6, 8, and 24 hours post-dose on Cycle 2 Day 1 (Day 29)
measure: Averaged Plasma Concentration at Steady State (Cavg) of Dacomitinib and Its Metabolite PF-05199265
timeFrame: Pre-dose and 2, 4, 6, 8, and 24 hours post-dose on Cycle 2 Day 1 (Day 29)
measure: Minimum Observed Plasma Concentration (Cmin) of Dacomitinib and Its Metabolite PF-05199265
timeFrame: Pre-dose and 2, 4, 6, 8, and 24 hours post-dose on Cycle 2 Day 1 (Day 29)
measure: Fluctuation Coefficient Between Trough and Peak Plasma Concentration (DF) of Dacomitinib and Its Metabolite PF-05199265
timeFrame: Pre-dose and 2, 4, 6, 8, and 24 hours post-dose on Cycle 2 Day 1 (Day 29)
measure: Apparent Clearance (CL) of Dacomitinib
timeFrame: Pre-dose and 2, 4, 6, 8, and 24 hours post-dose on Cycle 2 Day 1 (Day 29)
measure: Pre-dose Plasma Concentrations (Ctrough) of Dacomitinib and Its Metabolite PF-05199265
timeFrame: Pre-dose on Day 1 of Cycle 2, 3, 4, 5 and 6
Other outcomes:
Locations:
city: Beijing
country: China
city: Changchun
country: China
city: Changsha
country: China
city: Chengdu
country: China
city: Chongqing
country: China
city: Fuzhou
country: China
city: Guangzhou
country: China
city: Hangzhou
country: China
city: Hefei
country: China
city: Nanning
country: China
city: Shanghai
country: China
city: Shenyang
country: China
city: Tianjin
country: China
city: Wuhan
country: China
city: Wuxi
country: China
city: Hong Kong
country: Hong Kong
city: Shatin
country: Hong Kong
city: Catania
country: Italy
city: Lecco
country: Italy
city: Livorno
country: Italy
city: Meldola
country: Italy
city: Milano
country: Italy
city: Napoli
country: Italy
city: Perugia
country: Italy
city: Ravenna
country: Italy
city: Roma
country: Italy
city: Trento
country: Italy
city: Viterbo
country: Italy
city: Hokkaido
country: Japan
state: Asahikawa
city: Kashiwa
country: Japan
state: Chiba
city: Matsuyama
country: Japan
state: Ehime
city: Yokohama
country: Japan
state: Kanagawa
city: Tokyo
country: Japan
state: Koto-ku
city: Osakasayama
country: Japan
state: Osaka
city: Sakai
country: Japan
state: Osaka
city: Sunto-gun
country: Japan
state: Shizouka
city: Chuo-Ku
country: Japan
state: Tokyo
city: Seoul
country: Korea, Republic of
city: Gdansk
country: Poland
city: Olsztyn
country: Poland
city: Poznan
country: Poland
city: Warszawa
country: Poland
city: Avila
country: Spain
city: Barcelona
country: Spain
city: Bilbao
country: Spain
city: Caceres
country: Spain
city: Cordoba
country: Spain
city: Las Palmas
country: Spain
city: Madrid
country: Spain
city: Malaga
country: Spain
city: San Sebastian
country: Spain
city: Seville
country: Spain
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.