DARMSTADT, Germany and NEW YORK, November 19, 2018 /PRNewswire/ --
Not intended for US, Canada and UK-based media
Merck and Pfizer Inc. today announced that the Phase III JAVELIN Ovarian 200 trial evaluating avelumab* alone or in combination with pegylated liposomal doxorubicin (PLD), a type of chemotherapy, compared with PLD did not meet the prespecified primary endpoints of overall survival (OS) or progression-free survival (PFS) in patients with platinum-resistant or -refractory ovarian cancer. Signals were observed in the combination arm relative to PLD, and further analyses of the trial are warranted (HR for the primary PFS endpoint for avelumab + PLD vs PLD alone: 0.78 [repeated confidence interval (RCI): 0.587, 1.244; one-sided p-value: 0.0301]; HR for the primary OS endpoint for avelumab + PLD vs PLD alone: 0.89 [RCI: 0.744, 1.241; one-sided p-value: 0.2082]; HR for the primary PFS endpoint for avelumab alone vs PLD alone: 1.68 [RCI: 1.320, 2.601; one-sided p-value: >0.99]; HR for the primary OS endpoint for avelumab alone vs PLD alone: 1.14 [RCI: 0.948, 1.580; one-sided p-value: 0.8253]; objective response, a secondary endpoint: 13.3% [95% CI 8.8, 19.0] for avelumab + PLD; 3.7% [95% CI 1.5, 7.5] for avelumab alone; and 4.2% [95% CI 1.8, 8.1] for PLD alone). No new safety signals were observed for avelumab alone or in combination, and the safety profile for avelumab in this trial was consistent with that observed in the overall JAVELIN clinical development program. The data are currently being analyzed, and detailed results will be shared with the scientific community.
"JAVELIN Ovarian 200 enrolled a high proportion of patients with aggressive, refractory disease that had no response to prior platinum-based chemotherapy, a population known to have disease that is challenging to treat; as such, this group of patients is typically not included in Phase III ovarian cancer trials," said Chris Boshoff, M.D., Ph.D., Senior Vice President and Head of Immuno-Oncology, Early Development and Translational Oncology, Pfizer Global Product Development. "We initiated the JAVELIN Ovarian 200 trial as the first Phase III study of a checkpoint inhibitor in the platinum-resistant or -refractory setting recognizing these patients have the most pressing need for new treatment options. The results speak to the significant challenges these women face."
"Although OS and PFS did not reach statistical significance, study results indicate potential clinical activity of the combination of avelumab and chemotherapy which will be analyzed further," said Luciano Rossetti, M.D., Executive Vice President, Global Head of Research & Development at the Biopharma business of Merck. "We thank the patients, their families and the investigators who participated in the JAVELIN Ovarian 200 trial, and wish to underscore that the alliance remains committed to driving advances in ovarian cancer, a commitment that includes two ongoing Phase III trials in previously untreated patients testing avelumab in combination with chemotherapy and, separately, one in combination with chemotherapy followed by maintenance treatment of avelumab in combination with a PARP inhibitor."
"Effective management of platinum-resistant or -refractory ovarian cancer remains the biggest unmet medical need facing women with recurrent ovarian cancer today. The current treatment options have only limited and short-lived efficacy for the majority of women, as evidenced by an average life expectancy that does not exceed one year for this group," said Eric Pujade-Lauraine, M.D., Ph.D., head of the Women Cancers and Clinical Research Department at Hôpitaux Universitaires Paris Centre, site Hôtel-Dieu. "As a researcher and clinician, I know how important it is to continue to improve the outlook for women with advanced ovarian cancer and look forward to the results of more trials exploring the role of avelumab in delaying recurrence in platinum-sensitive patients and earlier lines of therapy."
Four out of five patients with ovarian cancer are diagnosed at advanced stages. The disease often has no symptoms early on, when it is much more treatable.1 Approximately 70% of patients with ovarian cancer who receive standard-of-care, frontline, platinum-based chemotherapy will relapse in the first three years.2 At first relapse, approximately 20% to 25% of ovarian cancer patients have platinum-resistant or -refractory disease, and eventually almost all patients will become platinum-resistant.3-6
JAVELIN Ovarian 200 is a Phase III, multicenter, randomized study investigating the efficacy and safety of avelumab alone or in combination with PLD versus PLD alone in 566 women with ovarian cancer that is resistant or refractory to platinum chemotherapy. The primary objectives were to demonstrate superior OS or PFS for one or both avelumab-based treatment regimens compared with PLD.
In addition to JAVELIN Ovarian 200, the avelumab ovarian cancer clinical development program includes several ongoing clinical trials investigating avelumab in combination with other therapies. JAVELIN Ovarian 100 is an open-label, international, multicenter, randomized Phase III study of avelumab in combination with and/or as follow-on (maintenance) treatment to platinum-based chemotherapy in previously untreated patients with locally advanced or metastatic (Stage III or Stage IV) epithelial ovarian cancer. JAVELIN Ovarian 100 is the first Phase III study to evaluate the addition of an immunotherapy to the standard of care in frontline treatment for this aggressive disease. JAVELIN Ovarian PARP 100 is a randomized, open-label, multicenter Phase III study of avelumab plus chemotherapy followed by maintenance therapy of avelumab in combination with a PARP inhibitor or chemotherapy followed by maintenance therapy with a PARP inhibitor, in patients with previously untreated advanced ovarian cancer. Avelumab is also undergoing investigation in combination with other therapies for gynecologic cancers.
*Avelumab is under clinical investigation for treatment of ovarian cancer and has not been demonstrated to be safe and effective for this indication. There is no guarantee that avelumab will be approved for ovarian cancer by any health authority worldwide.
About the JAVELIN Clinical Trial Program
The clinical development program for avelumab, known as JAVELIN, involves at least 30 clinical programs and more than 9,000 patients evaluated across more than 15 different tumor types. In addition to ovarian cancer, these tumor types include breast, gastric/gastro-esophageal junction and head and neck cancers, melanoma, mesothelioma, Merkel cell carcinoma, non-small cell lung cancer, renal cell carcinoma and urothelial carcinoma.
About Ovarian Cancer
Every year, more than 295,000 women are diagnosed with ovarian cancer worldwide.7 The disease is generally advanced when it is diagnosed, as it often has few to no symptoms at the early stages. This makes it difficult to detect until the disease has progressed. Symptoms can be vague or non-specific, making it easy to confuse with less serious non-cancerous conditions. The five-year survival rate ranges from approximately 30% to 50%, but for those with metastatic disease, it drops to less than 20%.7,8
Avelumab is a human anti-programmed death ligand-1 (PD-L1) antibody. Avelumab 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, avelumab has been shown to release the suppression of the T cell-mediated antitumor immune response in preclinical models.9-11 Avelumab has also been shown to induce NK cell-mediated direct tumor cell lysis via antibody-dependent cell-mediated cytotoxicity (ADCC) in vitro.11-13 In November 2014, Merck and Pfizer announced a strategic alliance to co-develop and co-commercialize avelumab.
Approved Indications in the US
In the US, the 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.
Avelumab is currently approved for patients with MCC in more than 35 countries globally, with the majority of these approvals in a broad indication that is not limited to a specific line of treatment.
Important Safety Information from the US FDA Approved Label
The warnings and precautions for BAVENCIO include immune-mediated adverse reactions (such as pneumonitis, hepatitis, colitis, endocrinopathies, nephritis and renal dysfunction, and other adverse reactions), infusion-related reactions and embryo-fetal toxicity.
Common adverse reactions (reported in at least 20% of patients) in patients treated with avelumab for mMCC and patients with locally advanced or mUC include fatigue, musculoskeletal pain, diarrhea, nausea, infusion-related reaction, peripheral edema, decreased appetite/hypophagia, urinary tract infection and rash.
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 avelumab, an anti-PD-L1 antibody initially discovered and developed by Merck. The immuno-oncology alliance is jointly developing and commercializing avelumab and advancing Pfizer's PD-1 antibody. The alliance is focused on developing high-priority international clinical programs to investigate avelumab 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 November 19, 2018. 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 avelumab, including clinical trials evaluating avelumab for the treatment of ovarian cancer, the Merck-Pfizer Alliance involving anti-PD-L1 and anti-PD-1 therapies, 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 avelumab; the uncertainties inherent in research and development, including the ability to meet anticipated clinical study commencement and completion dates and regulatory submission dates, as well as the possibility of unfavorable study results, including unfavorable new clinical data and additional analyses of existing clinical data; risks associated with interim data; the risk that clinical trial data are subject to differing interpretations, and, even when we view data as sufficient to support the safety and/or effectiveness of a product candidate, regulatory authorities may not share our views and may require additional data or may deny approval altogether; 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 in any jurisdictions for any potential indications for avelumab, combination therapies or other product candidates; whether and when regulatory authorities in any jurisdictions where applications are pending or may be submitted for avelumab, combination therapies or other product candidates may approve any such applications, which will depend on the assessment by such regulatory authorities of the benefit-risk profile suggested by the totality of the efficacy and safety information submitted; decisions by regulatory authorities regarding labeling and other matters that could affect the availability or commercial potential of avelumab, combination therapies or other product candidates; 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, 2017, 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 [http://www.pfizer.com ].
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