BAVENCIO Significantly Improved Overall Survival in Patients With Locally Advanced or Metastatic Urothelial Carcinoma

Author: Merck / 2023-07-23 21:27 / Source: Merck

BAVENCIO Significantly Improved Overall Survival in Patients With Locally Advanced or Metastatic Urothelial Carcinoma

Not intended for US-,Canada- and UK-based media

- At the planned interim analysis,Phase III JAVELIN Bladder 100 study met the primary endpoint of prolonging overall survival (OS) as a first-line maintenance treatment versus standard of care

-BAVENCIO is the first immunotherapy to significantly prolong OS in locally advanced or metastatic urothelial carcinoma (UC) in the first-line setting in a Phase III trial

DARMSTADT,Germany and NEW YORK,Jan. 6,2020 --Merck and Pfizer Inc. (NYSE: PFE) today announced the Phase III JAVELIN Bladder 100 study met its primary endpoint of overall survival (OS) at the planned interim analysis. In this study,patients with previously untreated locally advanced or metastatic urothelial carcinoma (UC) whose disease did not progress on induction chemotherapy and who were randomized to receive first-line maintenance therapy with BAVENCIO® (avelumab)* and best supportive care (BSC) lived significantly longer than those who received BSC only. A statistically significant improvement in OS was demonstrated in the BAVENCIO arm in each of the co-primary populations: all randomized patients and patients with PD-L1–positive tumors. The safety profile for BAVENCIO in the trial was consistent with that in the JAVELIN monotherapy clinical development program. The results of the study will be submitted for presentation at an upcoming medical congress and shared with the US Food and Drug Administration (FDA) and other health authorities.

"BAVENCIO is the first immunotherapy to demonstrate in a clinical trial a statistically significant improvement in overall survival as a first-line treatment for patients with advancedurothelial carcinoma," said Chris Boshoff,M.D.,Ph.D.,Chief Development Officer,Oncology,Pfizer Global Product Development."These latest positive data from the JAVELIN clinical development program add to the body of evidence for BAVENCIO in the treatment of genitourinary cancers,and we look forward to discussing these results with health authorities."

UC accounts for about 90% of all bladder cancer.1 When bladder cancer is metastatic,the five-year survival rate is 5%.2 Combination chemotherapy is currently the first-line standard of care for patients with advanced disease,but despite high initial response rates,durable and complete responses following first-line chemotherapy are uncommon,and most patients will ultimately experience disease progression within nine months after initiation of treatment.3,4

"Our unique maintenance approach with BAVENCIO has significantly prolonged survival for patients with locally advanced or metastatic urothelial carcinoma in this trial," said Luciano Rossetti,Executive Vice President,Head of Global R&D for the Biopharma business of Merck. "We believe this approach could become part of routine clinical practice,as these results are a major advance on the existing standard of care."

In 2017,the FDA approved BAVENCIO for the treatment of patients with locally advanced or metastatic urothelial carcinoma who have disease progression during or following platinum-containing chemotherapy,or who have disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy. This indication is approved under accelerated approval based on tumor response and duration of response. JAVELIN Bladder 100 is the confirmatory study for the conversion to full approval.

*BAVENCIO is under clinical investigation for the first-line maintenance treatment of advanced UC. There is no guarantee that BAVENCIO will be approved for first-line maintenance treatment of UC by any health authority worldwide.

About JAVELIN Bladder 100

JAVELIN Bladder 100 (NCT02603432) is a Phase III,multicenter,multinational,randomized,open-label,parallel-arm study investigating first-line maintenance treatment with BAVENCIO plus BSC versus BSC alone in patients with locally advanced or metastatic UC whose disease did not progress after completion of first-line platinum-containing chemotherapy. A total of 700 patients whose disease had not progressed after induction chemotherapy as per RECIST v1.1 were randomly assigned to receive either BAVENCIO plus BSC or BSC alone. The primary endpoint is OS in co-primary populations of all patients and patients with PD-L1—positive tumors. Secondary endpoints include progression-free survival,anti-tumor activity,safety,pharmacokinetics,immunogenicity,predictive biomarkers and patient-reported outcomes in the co-primary populations.

About Urothelial Carcinoma

Bladder cancer is the tenth most common cancer worldwide.5 In 2018,there were over half a million new cases of bladder cancer diagnosed,with around 200,000 deaths from the disease globally.5 UC accounts for about 90% of all bladder cancers.6 This subtype becomes harder to treat as it advances,spreading through the layers of the bladder wall.7 For patients with metastatic bladder cancer,the five-year survival rate is 5%.2 Given the poor prognosis for patients with advanced bladder cancer whose disease progresses after first-line chemotherapy,there is an urgent need for additional treatment options that improve overall survival.8

About the JAVELIN Clinical Development Program

The clinical development program for BAVENCIO,known as JAVELIN,involves more than 10,000 patients evaluated across more than 15 different tumor types. In addition to urothelial carcinoma,these tumor types include head and neck cancer,Merkel cell carcinoma,non-small cell lung cancer and renal cell carcinoma.

About BAVENCIO® (avelumab)

BAVENCIO is a human anti-programmed death ligand-1 (PD-L1) antibody. BAVENCIO has been shown in preclinical models to engage both the adaptive and innate immune functions. By blocking the interaction of PD-L1 with PD-1 receptors,BAVENCIO has been shown to release the suppression of the T cell-mediated antitumor immune response in preclinical models.9-11 In November 2014,Merck and Pfizer announced a strategic alliance to co-develop and co-commercialize BAVENCIO.

BAVENCIO Approved Indications

The European Commission has authorized the use of BAVENCIO in combination with axitinib for the first-line treatment of adult patients with advanced renal cell carcinoma (RCC). In September 2017,the European Commission granted conditional marketing authorization for BAVENCIO as a monotherapy for the treatment of adult patients with metastatic Merkel cell carcinoma (MCC).

In the US,BAVENCIO in combination with axitinib is indicated for the first-line treatment of patients with advanced renal cell carcinoma (RCC). Additionally,the US Food and Drug Administration (FDA) granted accelerated approval for avelumab (BAVENCIO®) for the treatment of (i) adults and pediatric patients 12 years and older with metastatic Merkel cell carcinoma (mMCC) and (ii) patients with locally advanced or metastatic urothelial carcinoma (mUC) who have disease progression during or following platinum-containing chemotherapy,or have disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy. These indications are approved under accelerated approval based on tumor response rate and duration of response. Continued approval for these indications may be contingent upon verification and description of clinical benefit in confirmatory trials.

BAVENCIO is currently approved for patients with MCC in 50 countries globally,with the majority of these approvals in a broad indication that is not limited to a specific line of treatment.

BAVENCIO Safety Profile from the EU Summary of Product Characteristics (SmPC)

The special warnings and precautions for use for BAVENCIO monotherapy include infusion-related reactions,as well as immune-related adverse reactions that include pneumonitis and hepatitis (including fatal cases),colitis,pancreatitis (including fatal cases),myocarditis (including fatal cases),endocrinopathies,nephritis and renal dysfunction,and other immune-related adverse reactions. The special warnings and precautions for use for BAVENCIO in combination with axitinib include hepatotoxicity.

The SmPC list of the most common adverse reactions with BAVENCIO monotherapy in patients with solid tumors includes fatigue,nausea,diarrhea,decreased appetite,constipation,infusion-related reactions,weight decreased and vomiting. The list of most common adverse reactions with BAVENCIO in combination with axitinib includes diarrhea,hypertension,fatigue,dysphonia,hypothyroidism,cough,headache,dyspnea,and arthralgia.

About Merck-Pfizer Alliance

Immuno-oncology is a top priority for Merck and Pfizer. The global strategic alliance between Merck and Pfizer enables the companies to benefit from each other's strengths and capabilities and further explore the therapeutic potential of BAVENCIO,an anti-PD-L1 antibody initially discovered and developed by Merck. The immuno-oncology alliance is jointly developing and commercializing BAVENCIO. The alliance is focused on developing high-priority international clinical programs to investigate BAVENCIO as a monotherapy as well as combination regimens,and is striving to find new ways to treat cancer.

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Pfizer Disclosure Notice

The information contained in this release is as of January 6,2020. Pfizer assumes no obligation to update forward-looking statementscontained in this release as the result of new information or future events or developments.

This release contains forward-looking information about BAVENCIO (avelumab),including a potential indication for first-line maintenance therapy and a second-line treatment indication approved in the U.S. for BAVENCIO for the treatment of patients with locally advanced or metastatic urothelial carcinoma,the alliance between Merckand Pfizer involving BAVENCIO and clinical development plans,including their potential benefits,that involves substantial risks and uncertainties that could cause actual results to differ materially from those expressed or implied by such statements. Risks and uncertainties include,among other things,uncertainties regarding the commercial success of BAVENCIO; the uncertainties inherent in research and development,including the ability to meet anticipated clinical endpoints,commencement and/or completion dates for our clinical trials,regulatory submission dates,regulatory approval dates and/or launch dates,as well as the possibility of unfavorable new clinical data and further analyses of existing clinical data; risks associated with interim data; the risk that clinical trial data are subject to differing interpretations and assessments by regulatory authorities; whether regulatory authorities will be satisfied with the design of and results from our clinical studies; whether and whenany drug applications may be filed for BAVENCIO for first-line maintenance therapy for locally advanced or metastatic urothelial carcinoma in any jurisdictions,the second-line treatment for locally advanced or metastatic urothelial carcinoma outside the U.S. or in any jurisdictions for any other potential indications for BAVENCIO or combination therapies; whether and when regulatory authorities in any jurisdictions where any applications are pending or may be submitted for BAVENCIO or combination therapies,including BAVENCIO for locally advanced or metastatic urothelial carcinoma may approve any such applications,which will depend on myriad factors,including making a determination as to whether the product's benefits outweigh its known risks and determination of the product's efficacy,and,if approved,whether they will be commercially successful; decisions by regulatory authorities impacting labeling,manufacturing processes,safety and/or other matters that could affect the availability or commercial potential of BAVENCIO,including BAVENCIO for locally advanced or metastatic urothelial carcinoma; and competitive developments.

A further description of risks and uncertainties can be found in Pfizer's Annual Report on Form 10-K for the fiscal year ended December 31,2018,and in its subsequent reports on Form 10-Q,including in the sections thereof captioned "Risk Factors" and "Forward-Looking Information and Factors That May Affect Future Results",as well as in its subsequent reports on Form 8-K,all of which are filed with the U.S. Securities and Exchange Commission and available at www.sec.gov and www.pfizer.com.

References

Cancer.net. Bladder Cancer: Introduction. https://www.cancer.net/cancer-types/bladder-cancer/introduction.Accessed January 2020.

SEER. Cancer Stat Facts: Bladder Cancer. https://seer.cancer.gov/statfacts/html/urinb.html. Accessed January 2020.

Bukhari N,et al. Update on the Treatment of Metastatic Urothelial Carcinoma. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6011065/. Accessed January 2020.

Von der Maase H,et al. Comparing Gemcitabine Plus Cisplatin,With Methotrexate,Vinblastine,Doxorubicin,Plus Cisplatin in patients With Bladder Cancer. Journal of Clinical Oncology. 2005;23(21):4602-4608.

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Cancer.net. Bladder Cancer: Introduction. https://www.cancer.net/cancer-types/bladder-cancer/introduction. Accessed January 2020.

American Cancer Society. What is Bladder Cancer? https://www.cancer.org/cancer/bladder-cancer/about/what-is-bladder-cancer.html. Accessed January 2020.

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Dahan R,Sega E,Engelhardt J,et al. FcγRs modulate the anti-tumor activity of antibodies targeting the PD-1/PD-L1 axis. Cancer Cell. 2015;28(3):285-295.

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