Date: 2016-06-06
Type of information: Presentation of results at a congress
phase: 2
Announcement: presentation of results at the American Society of Clinical Oncology (ASCO) annual meeting, in Chicago
Company: Merck Serono (Germany) Pfizer (USA - NY)
Product: MSB0010718C (avelumab)
Action
mechanism: monoclonal antibody/immune checkpoint inhibitor. MSB0010718C (avelumab) is a fully human IgG1 monoclonal antibody that binds to the PD-L1 (programmed death-ligand 1) protein, which is present at high levels in many cancer types. By competitively blocking the interaction with PD-1 receptors, it is believed that MSB0010718C thereby restores anti-tumor T-cell responses and inhibits tumor growth. Avelumab has received multiple regulatory designations in MCC from the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA), including Orphan Drug (FDA and EMA), Fast Track and Breakthrough status (FDA). There are plans to submit marketing applications for avelumab to regulatory authorities based on these data.
Disease: metastatic Merkel cell carcinoma
Therapeutic area: Cancer - Oncology
Country: Asia Pacific, Australia, Australia, Austria, France, Germany, Italy, Japan, Spain, Switzerland, USA
Trial
details: The JAVELIN Merkel 200 study is an international, multicenter, open-label, Phase II study of avelumab conducted in 88 patients with metastatic Merkel cell carcinoma (MCC). Patients in this study were generally elderly (median age was 72.5 years, range 33–88 years) and pre-treated, with at least one line of chemotherapy (one [59.1%], two [29.5%] or three or more [11.4%] previous treatments). Patients received avelumab 10 mg/kg intravenously once every two weeks. The protocol-defined analysis set for efficacy and safety consisted of all patients who received at least one dose of study treatment. The cut-off date for the planned primary analysis was 6 months after start of study treatment of the last patient. The primary endpoint of the study was confirmed best overall response according to RECIST v1.1 and assessed by an independent review committee. Secondary endpoints were duration of response, PFS, OS, response status by RECIST at 6 and 12 months, safety and tolerability, pharmacokinetics, and immunogenicity of avelumab. (NCT02155647)
Latest
news: * On June 6, 2016, Merck KGaA and Pfizer announced results from the first pivotal, international, multicenter, open-label, Phase II study of avelumab, which showed a 31.8% objective response rate (ORR) (28 of 88 patients; 95.9% CI: 21.9–43.1%†), in the pre-planned primary analysis of the study, and a manageable safety profile in patients with metastatic Merkel cell carcinoma (MCC) who were treated with avelumab in second or subsequent lines of therapy. Tumor responses were rapid, with 78.6% of patients (22 of 28) responding within 7 weeks of starting treatment, and durable, with 82.1% of patients (23 of 28) still responding at the time of analysis. No unexpected safety signals were reported. These data have been reported during an oral presentation at the 52nd American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago. In the trial, eight patients (9.1%) achieved complete responses and 20 patients (22.7%) achieved partial responses. The median duration of response has not been reached (95% CI: 8.3 months – not estimable; range, 2.8–17.5+ months). Tumor responses were seen in patients regardless of the status of certain biomarkers (PD-L1 and Merkel cell polyomavirus). The progression-free survival (PFS) rate at 6 months was 40% (95% CI: 29–50%, estimated by the Kaplan-Meier method). Early data also showed an overall survival (OS) rate at 6 months of 69% (95% CI: 58–78%) and a median OS of 11.3 months (7.5–14.0 months); however, these OS data are still maturing since minimum follow-up was 6 months for inclusion in this analysis. Treatment-related adverse events (AEs) occurred in 62 patients (70.5%); the most common were fatigue (23.9%) and infusion-related reactions (17.0%), all of which were Grade 1 or 2. Grade 3 treatment-related AEs were reported in four patients (4.5%). There were no Grade 4 treatment-related AEs or deaths. * On July 29, 2014, Merck Serono, the biopharmaceutical division of Merck KGaA, announced the initiation of an international Phase II study designed to assess the efficacy and safety of MSB0010718C, an investigational fully human IgG1 monoclonal antibody that binds to programmed death-ligand 1 (PD-L1). This multicenter, single-arm, open-label study is being conducted in patients with metastatic Merkel cell carcinoma (mMCC), a rare and aggressive type of skin tumor, who have previously received one line of chemotherapy. It is expected to recruit 84 patients across Asia Pacific, Australia, Europe and North America. The primary endpoint of the study is overall response. In addition to this new study in mMCC, MSB0010718C is currently being explored in a Phase I clinical trial for the treatment of solid tumors. The study aims to recruit 590 patients and has enrolled 422 patients to date. On June 1, 2014, Merck Serono presented initial data from this dose escalation study in solid tumors at the annual American Society of Clinical Oncology (ASCO) meeting in Chicago. This study is currently recruiting patients into expansion cohorts in seven cancer types: castrate-resistant prostate cancer, colorectal cancer, gastric/gastroesophageal cancer, melanoma, metastatic breast cancer, non-small cell lung cancer and ovarian cancer.
