On December 9, 2015 Merck and Pfizer reported the initiation of two Phase III studies of avelumab*, an investigational, fully human anti-PD-L1 IgG1 monoclonal antibody, in treating advanced or metastatic gastric/gastro-esophageal junction (GEJ) cancers, which are aggressive cancers with poor survival rates (Press release, Merck KGaA, DEC 9, 2015, View Sourcepfizer.com/news/press-release/press-release-detail/merck_kgaa_darmstadt_germany_and_pfizer_initiate_two_phase_iii_studies_of_investigational_immunotherapy_avelumab_in_advanced_gastric_and_gastro_esophageal_junction_cancers" target="_blank" title="View Sourcepfizer.com/news/press-release/press-release-detail/merck_kgaa_darmstadt_germany_and_pfizer_initiate_two_phase_iii_studies_of_investigational_immunotherapy_avelumab_in_advanced_gastric_and_gastro_esophageal_junction_cancers" rel="nofollow">View Source [SID:1234508513]). Schedule your 30 min Free 1stOncology Demo! These pivotal trials are investigating avelumab in the first-line and third-line settings, with overall survival (OS) as the primary endpoint in both trials.
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JAVELIN Gastric 100, a study comparing the switch from first-line chemotherapy to maintenance therapy with avelumab versus continuation of chemotherapy, is a multicenter, international, randomized, open-label Phase III trial designed to evaluate the potential superiority (based on OS) of maintenance therapy with avelumab in patients with unresectable, locally advanced or metastatic gastric/GEJ cancers whose disease has not progressed with first-line platinum-based chemotherapy. This is currently the only Phase III trial in gastric cancer that is designed to evaluate superiority of an immunotherapy compared with conventional platinum-based chemotherapy as a first-line maintenance treatment. The study will enroll 629 patients across more than 220 sites in Asia Pacific, Europe, North America and South America.
"The prognosis is generally poor for the majority of patients with advanced gastric cancers," said Dr. Luciano Rossetti, Head of Global Research & Development at Merck’s biopharma business. "By initiating these two Phase III trials in gastric and gastro-esophageal junction cancers, we are continuing the fight against cancer with an overarching goal of potentially improving survival for patients."
The third-line study, JAVELIN Gastric 300, is a multicenter, international, randomized, open-label Phase III trial designed to evaluate the potential superiority (based on OS) of avelumab in patients with unresectable, recurrent or metastatic gastric/GEJ cancers, compared with investigator’s choice of chemotherapy from a pre-specified list of therapeutic options. The study will enroll approximately 330 patients, spanning approximately 170 sites in Asia, Australia, Europe, North America and South America.
"We are continuing to investigate avelumab in cancers with high unmet need and where there is a strong rationale for immunotherapeutic intervention," said Dr. Mace Rothenberg, Senior Vice President of Clinical Development and Medical Affairs and Chief Medical Officer for Pfizer Oncology. "Advanced gastric cancer is a challenging diagnosis to face as a patient, and we are dedicating significant resources to evaluate avelumab as a potential new treatment option for patients in multiple settings of this disease."
The clinical development program for avelumab now includes more than 1,500 patients who have been treated across more than 15 tumor types, including breast cancer, gastric/GEJ cancers, head and neck cancer, Merkel cell carcinoma, melanoma, mesothelioma, non-small cell lung cancer, ovarian cancer, renal cell carcinoma and urothelial (e.g. bladder) cancer. Clinical trials for both of the gastric/GEJ Phase III trials in North America will be conducted on behalf of Merck by EMD Serono, the company’s US and Canadian biopharma business.
*Avelumab is the proposed International Non-proprietary Name for the anti-PD-L1 monoclonal antibody (MSB0010718C). Avelumab is under clinical investigation and has not been proven to be safe and effective. There is no guarantee any product will be approved in the sought-after indication by any health authority worldwide.
References
1. Waddell T et al. Ann Oncol 2013;24 Suppl 6:vi57-63.
2. Wadhwa R et al. Nat Rev Clin Oncol 2013;10(11):643-55.
3. American Cancer Society. Survival rates for stomach cancer, by stage. Available from: View Sourcecancer.org/cancer/stomachcancer/detailedguide/stomach-cancer-survival-rates." target="_blank" title="View Sourcecancer.org/cancer/stomachcancer/detailedguide/stomach-cancer-survival-rates." rel="nofollow">View Source Last accessed December 2015.
4. National Cancer Institute Surveillance Epidemiology and End Results (SEER). SEER Stat Fact Sheets: Stomach Cancer. Available from: View Source stomach.html. Last accessed April 2015.
5. International Agency for Research on Cancer (IARC)/EUCAN. Gastric cancer: Estimated incidence, mortality & prevalence for both sexes, 2012. Available from: http:// eco.iarc.fr/EUCAN/Cancer.aspx?Cancer=8#block-table-a. Last accessed April 2015.
6. Mayo Clinic. Stomach cancer treatments and drugs. Available from: View Source mayoclinic.org/diseases-conditions/stomach-cancer/basics/treatment/con-20038197. Last accessed April 2015.
7. Buas MF & Vaughan TL. Semin Radiat Oncol. 2013; 23(1): 3-9.
8. Cunningham D et al. New Eng J Med 2006;355(1):11-22.
9. Macdonald JS et al. N Eng J Med 2001;345(10):725-30.
10. Cancer Research UK. What is advanced oesophageal junction cancer? View Source cancerresearchuk.org/about-cancer/type/oesophageal-cancer/treatment/advanced/what-is-advanced-oesophageal-cancer. Last accessed September 2015.
About Gastric and Gastro-esophageal Junction (GEJ) Cancers
Gastric cancer is uncommon in the US and Western Europe.1,2 Each year, there are approximately 22,000 new cases of gastric cancer diagnosed in the US and 80,626 cases diagnosed in the EU.3 Gastric cancer is much more commonly diagnosed in East Asia, Eastern Europe, and parts of South America.4 For patients with advanced gastric cancer, the prognosis is poor. The 5-year survival rate in the US is <20 percent for Stage III gastric cancer and <5 percent for Stage IV gastric cancer.5 Current treatment options for gastric cancer may include surgery, radiotherapy, chemotherapy, chemoradiotherapy and targeted therapies.2,6
Reliable data on the global incidence of GEJ tumors are not available, due to the historically complicated classification system and the likelihood of misclassification.7 Current treatment options for GEJ cancer may include surgery, chemotherapy, radiation therapy and targeted therapy.8,9 Despite advances in the field of GEJ, there is no cure for patients with cancer that has spread.10 There is a clear unmet medical need for new treatment options.
About Avelumab
Avelumab (also known as MSB0010718C) is an investigational fully human anti-PD-L1 IgG1 monoclonal antibody. By inhibiting PD-L1 interactions, avelumab is thought to enable the activation of T-cells and the adaptive immune system. By retaining a native Fc-region, avelumab is thought to potentially engage the innate immune system and induce antibody-dependent cell-mediated cytotoxicity (ADCC). In November 2014, Merck and Pfizer announced a strategic alliance to co-develop and co-commercialize avelumab.