Avelumab Plus Axitinib Significantly Improved Progression-Free Survival In Previously Untreated Patients with Advanced Renal Cell Carcinoma in Phase III Study

San Francisco, CA (UroToday.com) -- Merck KGaA, Darmstadt, Germany, and Pfizer Inc. 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.

  • 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
  • The trial will continue for the other primary endpoint of overall survival; detailed results to be submitted for presentation at an upcoming medical congress
References
1.     National Cancer Institute: SEER Stat Fact Sheets: Kidney and renal pelvis. 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? 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. 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.
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