Merck (NYSE:MRK), known as MSD outside the United States and Canada, today announced additional data for MK-3475, an investigational anti-PD-1 immunotherapy, in patients with advanced melanoma that showed an estimated overall survival rate of 81 percent at one year across all MK-3475 monotherapy doses evaluated. This is the first time overall survival data have been presented from the cohort of 135 patients with advanced melanoma enrolled in Merck’s ongoing Phase IB clinical trial (PN 001) for MK-3475. Researchers presented the findings today in an oral plenary session at the 10th International Congress of the Society for Melanoma Research in Philadelphia. “New agents are needed for patients with advanced melanoma,” said Dr. Caroline Robert, head of Dermatology at Gustave Roussy, Cancer Campus, Grand Paris. “I am excited by the results seen for MK-3475 to date as a single agent and believe these findings support further study both as a monotherapy and in combination in various solid tumors.” The objective response rate (patients who had either a complete or partial response) across all doses improved with longer duration of follow-up; at the time of this analysis, the objective response rate was 41 percent (9 percent complete response rate), as evaluated by a blinded central review committee using RECIST 1.1 (Response Evaluation Criteria in Solid Tumors). While the majority of responses to MK-3475 treatment occurred early (within the first 12 weeks), responses and changes from partial to complete response continued to occur after six months of treatment. Partial and complete responses occurred as late as 48 and 70 weeks. Median duration of response and median overall survival have yet to be reached for any dose evaluated. “These results provide further insight into the therapeutic properties of MK-3475 in patients with advanced melanoma,” said Dr. Roger M. Perlmutter, president, Merck Research Laboratories. “Simply put, our data make us hopeful that this novel investigational therapy could potentially provide meaningful benefits to patients suffering from this malignant disease.”
Phase 1B Trial (PN 001) Trial DesignThe Phase IB trial (PN 001) is an ongoing multi-center, single-arm, open-label study evaluating MK-3475 monotherapy in more than 1,000 patients with diverse late-stage cancers (metastatic carcinoma)—predominantly lung and melanoma. Three dosing regimens of MK-3475 were evaluated, including 10mg/kg every two weeks, 10mg/kg every three weeks or 2mg/kg every three weeks. The primary endpoint of the study is overall response rate and the secondary endpoints are progression-free survival and overall survival as measured by immune-related response criteria and centrally evaluated RECIST criteria. Additional Results for MK-3475 in Advanced Melanoma This additional analysis provides approximately five months of follow-up for objective response rate beyond the interim results for MK-3475 from the 135 patients in the advanced melanoma cohort presented at the 2013 American Society of Clinical Oncology (ASCO) Annual meeting and published in the New England Journal of Medicine. In addition, this is the first time overall survival and progression-free survival have been presented from this study. The previously reported objective response rate across all doses was 38 percent (CI 95%: 25 to 44 percent) (per RECIST criteria). In the analysis presented today, the overall response rate was 41 percent (CI 95%: 32 to 51 percent), reflecting additional responses to MK-3475. In addition, 88 percent (43/49) of patients with a partial or complete response showed no evidence of disease progression. Similar response rates were observed between ipilimumab-pretreated and ipilimumab-naïve patients. At this analysis, the maximum ongoing duration of response recorded was 65 weeks (range 8+ to 65+). The disease control rate across doses for patients in the melanoma cohort was 61 percent (CI 95%: 52 to 70 percent), and median progression-free survival at time of analysis was 36 weeks. The rates of treatment-related adverse events were consistent with those previously observed and included: fatigue (37%), pruritus (26%), rash (22%), diarrhea (21%), arthralgia (17%), vitiligo (14%), headache (13%), nausea (12%), asthenia (11%), myalgia (11%) and AST increase (10%). Grade 3–4 treatment-related adverse events that occurred in more than one patient were AST increase, fatigue, rash and renal failure (n=2 each).
Clinical Development of MK-3475 in Advanced MelanomaMerck has completed enrollment in a Phase II registration trial (PN 002) comparing two doses of MK-3475 versus chemotherapy in patients with advanced melanoma who have progressed after prior therapy (see clinicaltrials.gov). A Phase III registration trial of MK-3475 versus ipilimumab in ipilimumab-naïve patients with advanced melanoma is ongoing (see clinicaltrials.gov). The company plans to initiate combination trials this year and in early 2014 in melanoma and other cancers. About MK-3475 Many tumors are able to evade the immune system through a mechanism that exploits the PD-1 inhibitory checkpoint protein. MK-3475 is an investigational, highly selective anti-PD-1 immunotherapy designed to restore the natural ability of the immune system to recognize and target cancer cells by selectively achieving dual ligand blockade (PD-L1 and PD-L2) of the PD-1 protein. By blocking PD-1, MK-3475 enables activation of the immune system’s T-cells that target cancer by essentially releasing a brake on the immune system. MK-3475 is currently being studied in eight clinical trials estimated to enroll over 3,000 patients across a broad range of cancer types, including: bladder, colorectal, gastric, head and neck, melanoma, non-small cell lung, triple negative breast and hematological malignancies. Additional trials, both as monotherapy and in combination with other cancer therapies, are planned. The expansion of the MK-3475 clinical development program is based on preliminary clinical evidence from Merck’s large foundational Phase IB trial (PN 001) evaluating MK-3475 monotherapy in more than 1,000 patients with diverse late-stage cancers (metastatic carcinoma). About Breakthrough Therapy Designation In April 2013, Merck announced that MK-3475 received a Breakthrough Therapy Designation for advanced melanoma from the U.S. Food and Drug Administration (FDA). This designation for an investigational drug is intended to expedite the development and review of a candidate that is planned for use, alone or in combination, to treat a serious or life-threatening disease or condition when preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over existing therapies on one or more clinically significant endpoints. The U.S. FDA Safety and Innovation Act includes a provision that allows sponsors to request that an investigational drug be designated as a Breakthrough Therapy.
About Advanced MelanomaOver one million new cases of skin cancer are diagnosed each year, and melanoma is the most dangerous type of skin cancer. While it accounts for only 5 percent of all cases, melanoma is the cause of 75 percent of skin cancer deaths. According to the American Cancer Society, an estimated 9,180 people in the U.S. died from advanced melanoma in 2012. About Merck Today's Merck is a global healthcare leader working to help the world be well. Merck is known as MSD outside the United States and Canada. Through our prescription medicines, vaccines, biologic therapies, and consumer care and animal health products, we work with customers and operate in more than 140 countries to deliver innovative health solutions. We also demonstrate our commitment to increasing access to healthcare through far-reaching policies, programs and partnerships. For more information, visit www.merck.com and connect with us on Twitter, Facebook and YouTube. Merck Forward-Looking Statement This news release includes “forward-looking statements” within the meaning of the safe harbor provisions of the United States Private Securities Litigation Reform Act of 1995. These statements are based upon the current beliefs and expectations of Merck’s management and are subject to significant risks and uncertainties. There can be no guarantees with respect to pipeline products that the products will receive the necessary regulatory approvals or that they will prove to be commercially successful. If underlying assumptions prove inaccurate or risks or uncertainties materialize, actual results may differ materially from those set forth in the forward-looking statements. Risks and uncertainties include, but are not limited to, general industry conditions and competition; general economic factors, including interest rate and currency exchange rate fluctuations; the impact of pharmaceutical industry regulation and healthcare legislation in the United States and internationally; global trends toward healthcare cost containment; technological advances, new products and patents attained by competitors; challenges inherent in new product development, including obtaining regulatory approval; Merck’s ability to accurately predict future market conditions; manufacturing difficulties or delays; financial instability of international economies and sovereign risk; dependence on the effectiveness of Merck’s patents and other protections for innovative products; and the exposure to litigation, including patent litigation, and/or regulatory actions.
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