DARMSTADT, Germany and NEW YORK, November 28, 2017 /PRNewswire/ --
Not intended for UK-based media
- Pivotal Phase III Javelin trial investigating avelumab as third-line treatment for patients with unresectable, recurrent or metastatic gastric cancer did not meet its pre-specified primary endpoint of superior overall survival compared to chemotherapy - First global trial of a checkpoint inhibitor versus an active chemotherapy comparator rather than placebo in this hard-to-treat patient population - Safety profile was consistent with that observed in previously reported studies of avelumab; no new safety signals were identified
Merck and Pfizer Inc. today announced that the Phase III JAVELIN Gastric 300 trial did not meet its primary endpoint of superior overall survival (OS) with single-agent avelumab* compared with physician's choice of chemotherapy. The trial investigated avelumab as a third-line treatment for unresectable, recurrent or metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma patients whose disease progressed following two prior therapeutic regimens, regardless of programmed death ligand-1 (PD-L1) expression. The safety profile of avelumab was consistent with that observed in the overall JAVELIN clinical development program.
"Gastric cancer in the third-line setting is a particularly hard-to-treat and heterogeneous disease, and importantly, this was the first trial conducted with a checkpoint inhibitor compared to an active chemotherapy comparator rather than placebo in a global patient population," said Luciano Rossetti, M.D., Executive Vice President, Global Head of Research & Development at the Biopharma business of Merck. "Data from this study will provide valuable information for physicians treating this late stage disease. We remain committed to our ongoing gastric cancer program with avelumab including the JAVELIN Gastric 100 study in the first-line switch maintenance setting."
"Gastric cancer is a leading cause of cancer death globally with clear unmet needs, and the results provide important insights as we continue to investigate the role of avelumab for the treatment of gastric cancer," said Chris Boshoff, M.D., Ph.D., Senior Vice President and Head of Immuno-Oncology, Early Development and Translational Oncology, Pfizer Global Product Development. "With approvals for two cancers in 2017, our companies have made tremendous progress with avelumab on behalf of patients this year, and we are confident that our broad clinical development program in both monotherapy and combinations across a range of cancers will continue to bring new potential treatment options to patients."
The JAVELIN Gastric 300 data will be further examined in an effort to better understand the results and will also be submitted for presentation at an upcoming medical congress. The outcome of JAVELIN Gastric 300 does not have any impact on current avelumab approvals.
JAVELIN Gastric 300 is a Phase III, multicenter, international, randomized, open-label clinical trial investigating avelumab plus best supportive care versus physician's choice of protocol-specified chemotherapy (paclitaxel or irinotecan monotherapy) plus best supportive care in patients with unresectable, recurrent or metastatic gastric or GEJ adenocarcinoma whose disease has progressed following two prior therapeutic regimens. The trial enrolled 371 patients from 147 sites in Asia, Australia, Europe, North America and South America. The primary endpoint was OS.
The avelumab gastric clinical development program also includes JAVELIN Gastric 100, a multicenter, randomized, open-label Phase III study evaluating avelumab as first-line maintenance therapy following induction chemotherapy in unresectable, locally advanced or metastatic gastric or GEJ cancer. The trial will continue as planned.
| Avelumab | is | under | clinical | investigation | for | treatment | of | gastric/GEJ | cancer | and | has | not | been | demonstrated | to | be | safe | and | effective | for | this | indication. | There | is | no | guarantee | that | avelumab | will | be | approved | for | gastric/GEJ | cancer | by | any | health | authority | worldwide |
About Gastric/Gastroesophageal Junction Cancer Globally, gastric cancer is the fifth most common cancer but the third most common cause of cancer death.[1],[2] In 2012, there were approximately 950,000 new cases and 723,000 deaths worldwide.[3] Of these cancers, 90 to 95 percent were adenocarcinomas.[4] Incidence varies by country, with higher rates seen in Central/Eastern Europe, Eastern Asia and South America.[5] Survival in advanced disease is poor and generally less than one year.[6] Globally, there is no recommended therapeutic approach for patients who progress after two lines of therapy for recurrent or metastatic gastric cancer.
About Avelumab 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.[7] -[9] Avelumab has also been shown to induce NK cell-mediated direct tumor cell lysis via antibody-dependent cell-mediated cytotoxicity (ADCC) in vitro.[9]-[11] In November 2014, Merck and Pfizer announced a strategic alliance to co-develop and co-commercialize avelumab.
Approved Indications 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 (MCC) and (ii) patients with locally advanced or metastatic urothelial carcinoma (UC) 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.
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 BAVENCIO for mMCC and patients with locally advanced or metastatic UC 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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