Merck, Pfizer Offers Results from Pivotal Avelumab Study

Merck

and Pfizer

today 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 will be reported today during an oral presentation at the 52nd American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, IL. "To see a tumor response in almost a third of patients in this trial, and for the majority to keep responding after six months, represents a potential breakthrough for this challenging disease," said lead investigator Howard L. Kaufman, M.D., FACS, Rutgers Cancer Institute of New Jersey, USA. "Currently, the only treatment option available for advanced stages of this aggressive type of skin cancer is chemotherapy, where the response rates are not adequate or durable." Metastatic MCC has a poor prognosis with less than 20% of patients surviving longer than five years.1 Although chemotherapy is considered a second-line treatment option for metastatic MCC, it is not a standard of care. Current guidelines recommend that these patients participate in clinical trials.2 "This is an important milestone for us as this is the largest data set of any anti-PD-L1 or anti-PD-1 reported to date in this patient population," said Luciano Rossetti, M.D., Executive Vice President, Global Head of Research & Development in the biopharma business of Merck. "The clinically meaningful tumor response rate for avelumab in metastatic Merkel cell carcinoma where chemotherapy has failed, reinforces our belief in the promise of this molecule, particularly considering the high unmet need in this disease." 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. "This has been an exciting ASCO for the strategic collaboration between the two companies, between the MCC data and the other encouraging responses observed across a broad range of tumors," said Chris Boshoff, M.D., PhD., Vice President and Head of Early Development, Translational and Immuno-Oncology at Pfizer Oncology. "The clinical benefits for avelumab as a monotherapy in notably hard-to-treat cancers may be amplified even further when combined with other therapies." 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.