Pfizer Unveils Positive Results from Asian Subgroup Analysis of ARCHER 1050

HONG KONG,Nov. 28,2019 -- Pfizer Inc. (NYSE: PFE) today announced the efficacy and tolerability results from the subgroup analysis of Asian patients enrolled in the ARCHER 1050,a randomized,multicenter,multinational,open-label Phase 3 study evaluating the efficacy of VIZIMPRO® (dacomitinib)-- an epidermal growth factor inhibitor (EGFR) tyrosine kinase inhibitor (TKI)-- as first-line monotherapy in patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with EGFR-activating mutations. The results,which were announced at ESMO Asia Congress 2019,show significant prolongation of progression-free survival (PFS); and an extended follow-up demonstrated significant improvement in overall survival (OS) with first-line dacomitinib versus gefitinib in Asian patients with EGFR-positive advanced NSCLC.

The subgroup analysis involved a subset of 346 Asian patients who were enrolled in Mainland China,Hong Kong SAR,Japan and Korea. Data cutoff dates were July 29,2016 for the PFS analysis and May 13,2019 for the extended OS analysis.

When treated with first-line VIZIMPRO®,the subgroup of Asian patients achieved significant prolongation of PFS (as determined by blinded Independent Radiologic Central (IRC) review) compared with gefitinib (HR = 0.509 [95% CI: 0.391,0.662],2-sided p<0.0001). Patients who were randomized to receive once-daily VIZIMPRO® achieved a median PFS of 16.5 months (95% CI: 12.9,18.4) compared with 9.3 months (95% CI: 9.2,11.0) in the gefitinib arm.[1]

In 2017,the analysis of the intent-to-treat population of ARCHER 1050 reported that the median PFS was 14.7 months in the VIZIMPRO® group (95% CI: 11.1,16.6) versus 9.2 months (95% CI: 9.1,11.0) in the gefitinib group.[2] The Asian subgroup analysis presented today demonstrates that treatment with first-line dacomitinib results in significant prolongation of PFS compared with gefitinib in Asian patients. "The results from the current subgroup analysis provide us with a more robust confirmation of the efficacy of dacomitinib as a first-line treatment option for Asian patients with EGFR-positive advanced NSCLC," said Professor Tony Mok,Specialist in Medical Oncology,who presented the results.

An extended follow-up of the Asian subgroup (median of 47.9 months for both treatment arms) demonstrated that dacomitinib resulted in significant improvements in the secondary efficacy endpoints of OS and duration of response (DoR) versus gefitinib. Median OS was 37.7 months (95% CI: 30.2,44.7) for dacomitinib patients versus 29.1 months for gefitinib (95% CI: 25.6,36.0) (HR for OS = 0.759 [95% CI: 0.578,0.996] favoring VIZIMPRO®). Median DoR in the VIZIMPRO® group was double that of the gefitinib group (16.6 months [95%CI: 13.8,30.4] versus 8.3 months [95% CI: 8.1,10.2],respectively).

Significantly,this OS benefit was maintained in patients who had a dose reduction. "We reported,in both the intent-to-treat population as well as the Asian subgroup,that OS benefit was maintained in patients who had a dose modification with dacomitinib at 30mg or 15mg QD. This is important as dose modification is the most effective way to manage toxicity,thereby enabling therapy to be better tolerated without compromising on efficacy of treatment," said Professor Mok.

The Asian subgroup analysis also showed that VIZIMPRO® had longer duration of treatment (DoT) compared with gefitinib (77.9 weeks vs. 52.7 weeks). Similar to the as-treated population of ARCHER 1050,the most commonly observed adverse events (AEs) in VIZIMPRO®-treated patients of this Asian subgroup were diarrhea (90.6%),paronychia (64.7%) and dermatitis acneiform (56.5%). No clinically relevant differences in overall frequency of all-cause AEs were observed between the Asian subgroup and the as-treated patient population. Overall,the rates of dose reductions or dosing interruptions were similar in both the Asian subgroup and the as-treated population.

[1] Pfizer. Data on file.

[2] Wu YL,Cheng Y,Zhou X,et al. 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;18(11):1454-1466.

About VIZIMPRO® (dacomitinib),45 mg,30 mg and 15 mg tablets

VIZIMPRO is an oral,once-daily,irreversible pan-human epidermal growth factor receptor kinase inhibitor. VIZIMPRO is approved in Canada,Mainland China,European Union (EU),Japan,Switzerland and the United States (US) for the first-line treatment of adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR)-activating mutations (exon 19 deletion or exon 21 L858R substitution mutations as detected by an FDA-approved test). The applications in the Mainland China,and the US were reviewed under the Priority Review program.

VIZIMPRO is approved in the US for the first-line treatment of patients with metastatic non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 19 deletion or exon 21 L858R substitution mutations as detected by an FDA-approved test.

In 2012,Pfizer and SFJ Pharmaceuticals entered into a collaborative development agreement to conduct ARCHER 1050 across multiple sites. SFJ is a global drug development company,which provides a unique and highly customized co-development partnering model for the world's top pharmaceutical and biotechnology companies. Under the terms of this agreement,SFJ Pharmaceuticals provided the funding and conducted the trial to generate the clinical data used to support this application. Pfizer retains all rights to commercialize VIZIMPRO globally.

About ARCHER 1050

The efficacy of VIZIMPRO was demonstrated in ARCHER 1050,a global Phase 3 head-to-head trial conducted in patients with unresectable,metastatic or recurrent non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) exon 19 deletion or exon 21 L858R substitution mutations,with no prior therapy for metastatic disease or recurrent disease with a minimum of 12 months disease-free after completion of systemic therapy. A total of 452 patients were randomized 1:1 to VIZIMPRO 45 mg (n=227) or gefitinib 250 mg (n=225). Randomization was stratified by region and EGFR mutation status. The primary endpoint of the study was progression-free survival (PFS) as determined by blinded Independent Radiology Central (IRC) review. Key secondary endpoints included PFS assessed by the investigator,objective response rate (ORR),duration of response (DoR),duration of treatment (DoT),overall survival (OS),and patient-reported outcomes (PROs).

VIZIMPRO® (dacomitinib) IMPORTANT SAFETY INFORMATION FROM THE U.S. PRESCRIBING INFORMATION

There are no contraindications for VIZIMPRO.

Interstitial Lung Disease (ILD): Severe and fatal ILD/pneumonitis occurred in patients treated with VIZIMPRO and occurred in 0.5% of the 394 VIZIMPRO-treated patients; 0.3% of cases were fatal. Monitor patients for pulmonary symptoms indicative of ILD/pneumonitis. Withhold VIZIMPRO and promptly investigate for ILD in patients who present with worsening of respiratory symptoms which may be indicative of ILD (e.g.,dyspnea,cough,and fever). Permanently discontinue VIZIMPRO if ILD is confirmed.

Diarrhea: Severe and fatal diarrhea occurred in patients treated with VIZIMPRO. Diarrhea occurred in 86% of the 394 VIZIMPRO-treated patients. Grade 3 or 4 diarrhea was reported in 11% of patients and 0.3% of cases were fatal. Withhold VIZIMPRO for Grade 2 or greater diarrhea until recovery to less than or equal to Grade 1 severity,then resume VIZIMPRO at the same or a reduced dose depending on the severity of diarrhea. Promptly initiate anti-diarrheal treatment (loperamide or diphenoxylate hydrochloride with atropine sulfate) for diarrhea.

Dermatologic Adverse Reactions: Rash and exfoliative skin reactions occurred in patients treated with VIZIMPRO. Rash occurred in 78% of the 394 VIZIMPRO-treated patients. Grade 3 or 4 rash was reported in 21% of patients. Exfoliative skin reactions of any severity were reported in 7% of patients. Grade 3 or 4 exfoliative skin reactions were reported in 1.8% of patients. Withhold VIZIMPRO for persistent Grade 2 or any Grade 3 or 4 dermatologic adverse reaction until recovery to less than or equal to Grade 1 severity,then resume VIZIMPRO at the same or a reduced dose depending on the severity of the dermatologic adverse reaction. The incidence and severity of rash and exfoliative skin reactions may increase with sun exposure. At the time of initiation of VIZIMPRO,initiate use of moisturizers and appropriate measures to limit sun exposure. Upon development of Grade 1 rash,initiate treatment with topical antibiotics and topical steroids. Initiate oral antibiotics for Grade 2 or more severe dermatologic adverse reactions.

Embryo-Fetal Toxicity: VIZIMPRO can cause fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to the fetus. Advise females of reproductive potential to use effective contraception during treatment with VIZIMPRO and for at least 17 days after the final dose.

Adverse Reactions: The most common (>20%) adverse reactions were diarrhea (87%),rash (69%),paronychia (64%),stomatitis (45%),decreased appetite (31%),dry skin (30%),decreased weight (26%),alopecia (23%),cough (21%),and pruritus (21%). The most common (more than or equal to 1%) serious adverse reactions were diarrhea (2.2%) and interstitial lung disease (1.3%).

Drug Interactions: Concomitant use with a proton pump inhibitor (PPI) decreases dacomitinib concentrations,which may reduce VIZIMPRO efficacy. Avoid the concomitant use of PPIs with VIZIMPRO. As an alternative to PPIs,use locally-acting antacids or an H2-receptor antagonist. Administer VIZIMPRO at least 6 hours before or 10 hours after taking an H2-receptor antagonist. Concomitant use of VIZIMPRO increases the concentration of drugs that are CYP2D6 substrates which may increase the risk of toxicities of these drugs. Avoid concomitant use of VIZIMPRO with CYP2D6 substrates where minimal increases in concentration of the CYP2D6 substrate may lead to serious or life-threatening toxicities.

Lactation: Because of the potential for serious adverse reactions in breastfed infants from VIZIMPRO,advise women not to breastfeed during treatment with VIZIMPRO and for at least 17 days after the last dose.

Hepatic Impairment: No dose adjustment is recommended in patients with mild or moderate hepatic impairment. The recommended dose of VIZIMPRO has not been established for patients with severe hepatic impairment.

Renal Impairment: No dose adjustment is recommended for patients with mild or moderate renal impairment. The recommended dose of VIZIMPRO has not been established for patients with severe renal impairment.

Please see full prescribing information at Pfizer.com

About Non-Small Cell Lung Cancer

Lung cancer is the most common cancer worldwide,with more than two million new cases diagnosed globally in 2018.1 About 85 percent of all lung cancers are identified as non-small cell,and approximately 75 percent of these are metastatic,or advanced,at diagnosis.

EGFR is a protein that helps cells grow and divide. When the EGFR gene is mutated it can cause the protein to be overactive resulting in cancer cells to form. EGFR mutations may occur in 10 to 35 percent of NSCLC tumors globally,and the most common activating mutations are deletions in exon 19 and exon 21 L858R substitution,which together account for more than 80 percent of known activating EGFR mutations. The disease is associated with low survival rates and disease progression remains a challenge.

About Pfizer in Lung Cancer

Pfizer Oncology is committed to addressing the unmet needs of patients with lung cancer,the leading cause of cancer-related deaths worldwide and a particularly difficult-to-treat disease. Pfizer strives to address the diverse and evolving needs of patients with non-small cell lung cancer (NSCLC) by developing efficacious and tolerable therapies,including biomarker-driven therapies. By combining leading scientific insights with a patient-centric approach,Pfizer is continually advancing its work to match the right patient with the right medicine at the right time. Through our research and collaboration efforts,we are committed to delivering renewed hope to patients living with NSCLC.

About Pfizer Oncology

At Pfizer Oncology,we are committed to advancing medicines wherever we believe we can make a meaningful difference on the lives of patients. Today,Pfizer Oncology has an industry-leading portfolio of 22 approved innovative cancer medicines and biosimilars across more than 30 indications,including breast,prostate,kidney and lung cancers,as well as leukemia and melanoma.

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