BAVENCIO® (avelumab) Plus INLYTA® (axitinib) Significantly Improved Progression-Free Survival in Previously Untreated Pa

DARMSTADT, Germany and NEW YORK, September 11, 2018 /PRNewswire/ --

Not intended for US, Canada and UK-based media 

- First positive Phase III immunotherapy trial in combination with a tyrosine kinase inhibitor (TKI) in any tumor type   - Results significant in both PDL1+ and all-comer populations  - Alliance plans to pursue a regulatory submission in the US and discussions with other health authorities based on interim results for progression-free survival   - Trial will continue for the other primary endpoint of overall survival; detailed results to be submitted for presentation at an upcoming medical congress 

Merck and Pfizer Inc. today announced positive top-line results from the pivotal Phase III JAVELIN Renal 101 study evaluating BAVENCIO(R) (avelumab)* in combination with INLYTA(R) (axitinib)*, compared with SUTENT(R) (sunitinib) as initial therapy for patients with advanced renal cell carcinoma (RCC). As part of a planned interim analysis, an independent Data Monitoring Committee confirmed that the trial showed a statistically significant improvement in progression-free survival (PFS) by central review for patients treated with the combination whose tumors had programmed death ligand-1--positive (PD-L1+) expression greater than 1% (primary objective), as well as in the entire study population regardless of PD-L1 tumor expression (secondary objective). According to the statistical analysis plan, if PFS was statistically significant in the PD-L1+ subgroup, then PFS in the entire study population was to be analyzed for statistical significance. JAVELIN Renal 101 will continue as planned to the final analysis for the other primary endpoint of overall survival (OS). No new safety signals were observed, and adverse events for BAVENCIO, INLYTA and SUTENT in this trial were consistent with the known safety profiles for all three medicines. The alliance intends to pursue a regulatory submission in the US based on these interim results, and these results will be discussed with global health authorities. A detailed analysis will also be submitted for presentation at an upcoming medical congress.

"JAVELIN Renal 101 is the first positive Phase III study combining an immune checkpoint blocker with a TKI, supporting the potential of BAVENCIO and INLYTA as a new cancer treatment approach for patients with advanced RCC," said Chris Boshoff, M.D., Ph.D., Senior Vice President and Head of Immuno-Oncology, Early Development and Translational Oncology, Pfizer Global Product Development. "These positive results reinforce Pfizer's long-standing heritage in advancing standards of care for people with RCC, and we look forward to discussing these data in greater detail with health authorities."

In December 2017, the US Food and Drug Administration (FDA) granted Breakthrough Therapy Designation for BAVENCIO in combination with INLYTA for treatment-naïve patients with advanced RCC. Despite available therapies, the outlook for patients with advanced RCC remains poor.[1] Approximately 20% to 30% of patients are first diagnosed at the metastatic stage.[2] The five-year survival rate for patients with metastatic RCC is approximately 12%.[1]

"We are encouraged by these data which illustrate the impact of BAVENCIO in combination with INLYTA as a potential first-line treatment for people with advanced RCC, a serious and life-threatening cancer," said Luciano Rossetti, M.D., Executive Vice President, Global Head of Research & Development at the Biopharma business of Merck. "They also support our firm belief in the promise of combining BAVENCIO with currently approved therapies and novel agents, a strong focus of the overall JAVELIN clinical development program."

JAVELIN Renal 101 is a global Phase III, multicenter, randomized (1:1) study investigating the efficacy and safety of BAVENCIO in combination with INLYTA as a first-line treatment option compared with SUTENT monotherapy in 886 patients with advanced RCC across all risk groups. The primary objectives are to demonstrate that BAVENCIO in combination with INLYTA is superior to SUTENT monotherapy in prolonging PFS or OS in patients with PD-L1+ tumors. BAVENCIO was administered at 10 mg/kg IV every two weeks in combination with INLYTA at 5 mg orally twice daily; SUTENT was administered at 50 mg orally once daily, four weeks on/two weeks off.

About the JAVELIN Clinical Development Program 

The clinical development program for BAVENCIO, known as JAVELIN, involves at least 30 clinical programs, eight Phase III trials and more than 8,600 patients evaluated across more than 15 different tumor types. In addition to RCC, these tumor types include breast, gastric/gastro-esophageal junction, head and neck, Hodgkin's lymphoma, melanoma, mesothelioma, Merkel cell carcinoma, non-small cell lung cancer, ovarian and urothelial carcinoma.

About Renal Cell Carcinoma  

RCC is the most common form of kidney cancer, accounting for about 2% to 3% of all cancers in adults.[3],[4] The most common type of RCC is clear cell carcinoma, accounting for approximately 70% of all cases.[3] In 2012, there were approximately 338,000 new cases of RCC diagnosed worldwide, with an estimated 63,340 cases expected in the US alone in 2018.[3],[5] Incidence varies substantially worldwide, with generally higher rates seen in North America and Central/Eastern Europe.[5]

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.[6] -[8] BAVENCIO has also been shown to induce NK cell-mediated direct tumor cell lysis via antibody-dependent cell-mediated cytotoxicity (ADCC) in vitro.[8]-[10] In November 2014, Merck and Pfizer announced a strategic alliance to co-develop and co-commercialize BAVENCIO.

Approved Indications  

The FDA granted accelerated approval for 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 also approved by the European Medicines Agency (EMA) for use in the EU as a monotherapy for the treatment of adult patients with mMCC.

Important Safety Information from the US FDA Approved Label 

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