BAVENCIO® (avelumab) Plus INLYTA® (axitinib) Significantly Improved Progression-Free Survival in Previously Untreated Patients with Advanced Renal Cell Carcinoma in Phase III Study

  • 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

September 11, 2018 I Merck KGaA, Darmstadt, Germany, and Pfizer Inc. (NYSE: PFE) today announced positive top-line results from the pivotal Phase III JAVELIN Renal 101 study evaluating BAVENCIO® (avelumab) in combination with INLYTA® (axitinib), compared with SUTENT® (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 KGaA, Darmstadt, Germany, which in the US and Canada operates as EMD Serono. “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.

*The combination of BAVENCIO and INLYTA is under clinical investigation for advanced RCC, and there is no guarantee this combination will be approved for advanced RCC by any health authority worldwide. In the US, INLYTA is approved as monotherapy for the treatment of advanced RCC after failure of one prior systemic therapy. INLYTA is also approved by the European Medicines Agency (EMA) for use in the EU in adult patients with advanced RCC after failure of prior treatment with SUTENT or a cytokine.

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® (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 KGaA, Darmstadt, Germany, 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.

About INLYTA® (axitinib)

INLYTA is an oral therapy that is designed to inhibit tyrosine kinases, including vascular endothelial growth factor (VEGF) receptors 1, 2 and 3; these receptors can influence tumor growth, vascular angiogenesis and progression of cancer (the spread of tumors). In the US, INLYTA is approved for the treatment of advanced renal cell carcinoma (RCC) after failure of one prior systemic therapy. INLYTA is also approved by the European Medicines Agency (EMA) for use in the EU in adult patients with advanced RCC after failure of prior treatment with sunitinib or a cytokine.

About SUTENT® (sunitinib malate)

Sunitinib is a small molecule that inhibits multiple receptor tyrosine kinases, some of which are implicated in tumor growth, pathologic angiogenesis, and metastatic progression of cancer. Sunitinib was evaluated for its inhibitory activity against a variety of kinases (>80 kinases) and was identified as an inhibitor of platelet-derived growth factor receptors (PDGFRα and PDGFRβ), vascular endothelial growth factor receptors (VEGFR1, VEGFR2 and VEGFR3), stem cell factor receptor (KIT), Fms-like tyrosine kinase-3 (FLT3), colony stimulating factor receptor Type 1 (CSF-1R), and the glial cell-line derived neurotrophic factor receptor (RET).

SUTENT is indicated in the US for the treatment of gastrointestinal stromal tumor (GIST) after disease progression on or intolerance to imatinib mesylate; the treatment of advanced renal cell carcinoma (RCC); the adjuvant treatment of adult patients at high risk of recurrent RCC following nephrectomy; the treatment of progressive, well-differentiated pancreatic neuroendocrine tumors (pNET) in patients with unresectable locally advanced or metastatic disease.

About Merck KGaA, Darmstadt, Germany

Merck KGaA, Darmstadt, Germany, is a leading science and technology company in healthcare, life science and performance materials. Almost 53,000 employees work to further develop technologies that improve and enhance life - from biopharmaceutical therapies to treat cancer or multiple sclerosis, cutting-edge systems for scientific research and production, to liquid crystals for smartphones and LCD televisions. In 2017, Merck KGaA, Darmstadt, Germany, generated sales of € 15.3 billion in 66 countries.

Founded in 1668, Merck KGaA, Darmstadt, Germany, is the world's oldest pharmaceutical and chemical company. The founding family remains the majority owner of the publicly listed corporate group. Merck KGaA, Darmstadt, Germany holds the global rights to the "Merck" name and brand except in the United States and Canada, where the company operates as EMD Serono, MilliporeSigma and EMD Performance Materials.

Pfizer Inc.: Working together for a healthier world®

At Pfizer, we apply science and our global resources to bring therapies to people that extend and significantly improve their lives. We strive to set the standard for quality, safety and value in the discovery, development and manufacture of health care products. Our global portfolio includes medicines and vaccines as well as many of the world's best-known consumer health care products. Every day, Pfizer colleagues work across developed and emerging markets to advance wellness, prevention, treatments and cures that challenge the most feared diseases of our time. Consistent with our responsibility as one of the world's premier innovative biopharmaceutical companies, we collaborate with health care providers, governments and local communities to support and expand access to reliable, affordable health care around the world. For more than 150 years, we have worked to make a difference for all who rely on us. We routinely post information that may be important to investors on our website at www.pfizer.com. In addition, to learn more, please visit us on www.pfizer.com and follow us on Twitter at @Pfizer and @Pfizer_News, LinkedIn, YouTube and like us on Facebook at Facebook.com/Pfizer.

References

1.     National Cancer Institute: SEER Stat Fact Sheets: Kidney and renal pelvis. Available from: http://seer.cancer.gov/statfacts/html/kidrp.html. Accessed July 2018.

2.     Ljungberg B, Campbell S and Cho H. The Epidemiology of Renal Cell Carcinoma. Eur Urol. 2011;60:615-621.

3.     American Cancer Society. What is kidney cancer? Available from: https://www.cancer.org/cancer/kidney-cancer/about.html. Accessed July 2018.

4.     Escudier B, Porta C, Schmidinger M et al Renal cell carcinoma: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Annal Oncol. 2014; 25(Suppl3):iii49-iii56.

5.     World Cancer Research Fund International: Kidney cancer statistics. Available from: http://www.wcrf.org/int/cancer-facts-figures/data-specific-cancers/kidne.... Accessed July 2018.

6.     Dolan DE, Gupta S. PD-1 pathway inhibitors: changing the landscape of cancer immunotherapy. Cancer Control. 2014;21(3):231-237.

7.     Dahan R, Sega E, Engelhardt J, Selby M, Korman AJ, Ravetch JV. FcγRs modulate the anti-tumor activity of antibodies targeting the PD-1/PD-L1 axis. Cancer Cell. 2015;28(3):285-295.

8.     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.

9.     Kohrt HE, Houot R, Marabelle A, et al. Combination strategies to enhance antitumor ADCC. Immunotherapy. 2012;4(5):511-527.

10.   Hamilton G, Rath B. Avelumab: combining immune checkpoint inhibition and antibody-dependent cytotoxicity. Expert Opin Biol Ther. 2017;17(4):515-523.

SOURCE: Pfizer

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