European Commission Approves BAVENCIO(R) (avelumab) Plus Axitinib Combination for First-Line Treatment of Patients With Advanced Renal Cell Carcinoma

PR81326

DARMSTADT, Germany, and NEW YORK, October 29, 2019 /PRNewswire-AsiaNet/ --

Not intended for US, Canada and UK-based media  

-- EU approval based on JAVELIN Renal 101 trial results demonstrating

significant improvement in progression-free survival with BAVENCIO in

combination with axitinib compared with sunitinib

-- Combination regimen approved across all IMDC prognostic risk groups and

irrespective of PD-L1 expression

Merck and Pfizer Inc. (NYSE: PFE) today announced that the European Commission

(EC) has approved BAVENCIO(R) (avelumab) in combination with axitinib for the

first-line treatment of adult patients with advanced renal cell carcinoma

(RCC). The approval was based on positive interim results from the Phase III

JAVELIN Renal 101 study, which demonstrated that BAVENCIO in combination with

axitinib significantly lowered risk of disease progression or death by 31% (HR:

0.69 [95% CI: 0.574-0.825; p less than 0.0001]) and nearly doubled objective

response rate (ORR; 52.5% [95% CI: 47.7-57.2] vs. 27.3% [95% CI: 23.2-31.6])

compared with sunitinib in patients with advanced RCC regardless of PD-L1

status. The study included patients across International Metastatic Renal Cell

Carcinoma Database Consortium (IMDC) prognostic risk groups. Improvement in

progression-free survival (PFS) was observed across pre-specified subgroups in

patients receiving the treatment combination.1 Merck and Pfizer have a global

strategic alliance to jointly develop and commercialize BAVENCIO.

"There is a high incidence of kidney cancer in Europe, and for the most common

type, renal cell carcinoma, we continue to need additional treatment options,

particularly for patients with advanced disease, where outcomes are poorest,"

said Professor James Larkin, Consultant Medical Oncologist at The Royal Marsden

NHS Foundation Trust and Professor at the Institute of Cancer Research (ICR).

"We've seen a demonstrated efficacy benefit and safety and tolerability profile

for avelumab in combination with axitinib across all prognostic risk groups in

patients with advanced renal cell carcinoma, so today's approval in Europe

brings an important option that can help healthcare professionals optimize

treatment strategies across risk stratification."

In 2018, an estimated 136,500 new cases of kidney cancer were diagnosed in

Europe, and approximately 54,700 people died from the disease.2 Many patients

living with advanced RCC do not go on to receive additional treatment after

first-line therapy,3,4 for reasons that may include poor performance status or

adverse events from their initial treatment.3,5,6 The five-year survival rate

for patients with advanced RCC is approximately 12%.7

"This first European approval of an anti-PD-L1 as part of a combination

treatment for advanced renal cell carcinoma builds on our commitment to

bringing innovative treatment options to patients with hard-to-treat cancers

through our extensive JAVELIN clinical trial program," said Rehan Verjee,

Global Head of Innovative Medicine Franchises for the Biopharma business of

Merck. "RCC is the most common form of kidney cancer, accounting for 90% of

diagnoses. We are now working to make BAVENCIO in combination with axitinib

available for patients with advanced renal cell carcinoma as quickly as

possible."

"The European Commission approval of BAVENCIO in combination with axitinib has

the potential to bring even more patients with advanced renal cell carcinoma a

new first-line treatment, and it allows us to continue to deliver on our more

than decade-long passion to do more for patients with kidney cancer," said Andy

Schmeltz, Global President, Pfizer Oncology. "We thank all of the researchers,

doctors, advocates, patients and their families who helped get us here today,

and we will continue in our fight against this advanced cancer."

The EC's decision follows the U.S. Food and Drug Administration (FDA) approval

of BAVENCIO in combination with axitinib for the first-line treatment of

patients with advanced RCC in May 2019. A supplemental application for BAVENCIO

in combination with axitinib in unresectable or metastatic RCC was submitted in

Japan in January 2019.

Additionally, with this approval, the posology section of the Summary of

Product Characteristics for BAVENCIO has been updated. The recommended dose of

BAVENCIO as monotherapy is 800 mg administered intravenously over 60 minutes

every 2 weeks. Administration of BAVENCIO should continue according to the

recommended schedule until disease progression or unacceptable toxicity. The

recommended dose of BAVENCIO in combination with axitinib is 800 mg

administered intravenously over 60 minutes every 2 weeks and axitinib 5 mg

orally taken twice daily (12 hours apart) with or without food until disease

progression or unacceptable toxicity.1

Data from JAVELIN Renal 101 Study Supporting Approval

This approval was based on interim data from the Phase III JAVELIN Renal 101

study, a randomized, multicenter, open-label study of BAVENCIO in combination

with axitinib in 886 patients with untreated advanced or metastatic RCC with a

clear cell component. The study included patients across risk groups

(International Metastatic Renal Cell Carcinoma Database Consortium [IMDC]: 21%

favorable, 62% intermediate and 16% poor; Memorial Sloan Kettering Cancer

Center [MSKCC]: 22% favorable, 65% intermediate and 11% poor). The primary

efficacy endpoints were progression-free survival (PFS) as assessed by a

Blinded Independent Central Review (BICR) using RECIST v1.1 and overall

survival (OS) in the first-line treatment of patients with advanced RCC who

have PD-L1-positive tumors (PD‑L1 expression level greater than equal to

1%). PFS based on BICR assessment per RECIST v1.1 and OS irrespective of

PD‑L1 expression, objective response (OR), time to response (TTR),

duration of response (DOR) and safety are included as secondary endpoints. The

study is continuing for OS.

In the analysis, BAVENCIO in combination with axitinib significantly improved

median PFS compared with sunitinib by more than five months in patients

irrespective of PD-L1 expression (13.3 months [95% CI: 11.1–15.3] vs. 8.0

months [95% CI: 6.7–9.8]). With a median follow-up for OS of 19 months, data

for the trial's other endpoint of OS were immature, with 27% of deaths, and the

trial is continuing as planned. The hazard ratio for OS in patients treated

with BAVENCIO in combination with axitinib compared with sunitinib was 0.80

(95% CI: 0.616, 1.027) at the interim analysis.

The most common adverse reactions were diarrhea (62.8%), hypertension (49.3%),

fatigue (42.9%), nausea (33.5%), dysphonia (32.7%), decreased appetite (26.0%),

hypothyroidism (25.2%), cough (23.7%), headache (21.3%), dyspnea (20.9%), and

arthralgia (20.9%).

About the JAVELIN Clinical Development Program

The clinical development program for avelumab, known as JAVELIN, involves at

least 30 clinical programs and more than 10,000 patients evaluated across more

than 15 different tumor types. In addition to RCC, these tumor types include

gastric/gastro-esophageal junction cancer, head and neck cancer, Merkel cell

carcinoma, non-small cell lung cancer and urothelial carcinoma.

About BAVENCIO(R) (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.8-10 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(R)) 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, nausea,

dysphonia, decreased appetite, 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 October 28, 2019. Pfizer

assumes no obligation to update forward-looking statements contained 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 new indication approved in the European Union for BAVENCIO in

combination with axitinib for the treatment of patients with advanced renal

cell carcinoma, the alliance between Merck and 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 and axitinib; 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 when any drug

applications may be filed for BAVENCIO in combination with axitinib in any

other jurisdictions or in any jurisdictions for any other potential indications

for BAVENCIO or combination therapies; whether and when the pending application

in Japan for BAVENCIO in combination with axitinib may be approved and whether

and when regulatory authorities in any jurisdictions where any other

applications are pending or may be submitted for BAVENCIO or combination

therapies, including BAVENCIO in combination with axitinib 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 or combination

therapies, including BAVENCIO in combination with axitinib; 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

BAVENCIO(R) (avelumab) EU SmPC. Available from: http://www.ema.europa.eu/ema/.

Accessed October 2019.

Ferlay J, Colombet M, Soerjomataram I, et al. Cancer incidence and mortality

patterns in Europe: Estimates for 40 countries and 25 major cancers in 2018.

Eur J Cancer. 2018;103:356-387.

Eggers H, Ivanyi P, Hornig M, Grünwald V. Predictive factors for second-line

therapy in metastatic renal cell carcinoma: a retrospective analysis. J Kidney

Cancer VHL. 2017;4(1):8-15.

Motzer R, et al. Nivolumab plus Ipilimumab versus Sunitinib in Advanced

Renal-Cell Carcinoma. The New England Journal of Medicine. 2018;378:1277-1290.

Eichelberg C, Vervenne WL, De Santis M, et al. SWITCH: A randomised,

sequential, open-label study to evaluate the efficacy and safety of

sorafenib-sunitinib versus sunitinib-sorafenib in the treatment of metastatic

renal cell cancer. Eur Urol. 2015;68;837-847.

Motzer RJ, Barrios CH, Kim TM, et al. Phase II randomized trial comparing

sequential first-line everolimus and second-line sunitinib versus first-line

sunitinib and second-line everolimus in patients with metastatic renal cell

carcinoma. J Clin Oncol. 2014;32:2765-2772.

Ridge C, Pua B, Madoff D. Epidemiology and staging of renal cell carcinoma.

Semin Intervent Radiol. 2014;31(1):3-8.

Dolan DE, Gupta S. PD-1 pathway inhibitors: changing the landscape of cancer

immunotherapy. Cancer Control. 2014;21(3):231-237.

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.

Boyerinas B, Jochems C, Fantini M, et al. Antibody-dependent cellular

cytotoxicity activity of a novel anti-PD-L1 antibody avelumab (MSB0010718C) on

human tumor cells. Cancer Immunol Res. 2015;3(10):1148-1157.

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