ORLANDO, FL, May 29, 2009 – Merck & Co., Inc. today previewed new clinical data on several investigational cancer agents that will be featured at this year’s American Society of Clinical Oncology (ASCO) meeting in Orlando. These candidates are part of Merck’s growing oncology pipeline, which includes small molecules, biologics and therapeutic vaccine candidates targeting multiple biological pathways involved in the development and progression of cancer. Data will be presented from studies of MK-2206, an investigational inhibitor of Akt; MK-1775, an investigational inhibitor of Wee1 kinase; and MK-0646, an investigational humanized monoclonal antibody that targets the insulin-like growth factor-1 receptor (IGF-1R).
“Our goal is to advance the treatment of cancer by discovering and developing novel ways to target processes that allow tumors to grow and spread,” said Gary Gilliland, M.D., Ph.D., senior vice president of Merck Research Laboratories and Oncology Franchise Head. “We are encouraged by the results of these early-stage clinical studies and look forward to further characterizing the therapeutic effects of these pipeline oncology candidates.”
The investigational agents highlighted at ASCO address two key areas of focus for Merck: the phosphatidylinositol-3(PI3) kinase signaling pathway, which regulates cancer cell proliferation, growth, survival and metabolism; and DNA damage repair and cell cycle check points, which may prevent cancer cells from undergoing programmed cell death (apoptosis), a natural process that eliminates damaged or abnormal cells.
A Phase I Study of MK-2206, an Oral Potent Allosteric Akt Inhibitor in Patients with Advanced Solid Tumor (Abstract #3503)
Oral Presentation; Monday, June 1, 2009, 2:15 p.m. – 2:30 p.m. EDT; Level 3, Chapin Theater W320
Results from this Phase I study suggest that MK-2206 as a single agent was generally well-tolerated at doses up to 60 milligrams (mg) administered every other day to patients with advanced solid tumors. Furthermore, the 60-mg dose of MK-2206 was associated with a substantial and sustained inhibition of Akt activity.
The primary objective of this Phase I trial was to evaluate the safety and tolerability of MK-2206 at doses ranging from 30 to 90 mg administered every other day in 28-day cycles. Dose escalation occurred in 19 patients. The most common adverse events at the maximum tolerated dose (MTD) of 60 mg every other day were: mild to moderate skin rash (38.8 percent), gastrointestinal symptoms (nausea, vomiting, diarrhea; 38.8 percent), itching (22.2 percent), hyperglycemia (11.1 percent) and fatigue (5.5 percent). Observed clinical activity included central tumor necrosis (death), decreased ascites (cancer-related fluid build-up), decreased peripheral edema (swelling), reduction of index lesions and a decrease in the levels of several biomarkers, including cancer antigen 125. Larger studies are needed to confirm these results. MK-2206 is an investigational allosteric inhibitor of the serine/threonine kinase Akt, a member of the PI3 kinase pathway that receives and relays signals promoting cell growth and survival. Akt is frequently abnormally activated in human solid tumors.
A Phase I and Pharmacological Study of MK-1775, a Wee1 Tyrosine Kinase Inhibitor, in Both Monotherapy and in Combination with Gemcitabine, Cisplatin or Carboplatin in Patients with Advanced Solid Tumors (Abstract #3510) Oral Presentation; Saturday, May 30, 2009, 3:30 p.m. - 3:45 p.m. EDT; Level 4, Valencia Room, W415A Initial results from this ongoing Phase I study showed that MK-1775 was generally well-tolerated and demonstrated early anti-tumor activity in combination with gemcitabine, cisplatin or carboplatin in patients with advanced solid tumors. To date, 44 patients have been treated with MK-1775. The MTD – a primary endpoint of the study – was not identified when MK-1775 was used as a monotherapy. Preliminary MTDs of MK-1775 in combination with gemcitabine (1000 mg/m2), cisplatin (75 mg/m2) or carboplatin (AUC5) were 200, 325 and 200 mg, respectively. Dose-limiting toxicities in patients receiving combination therapy included hematological and gastrointestinal toxicity, fatigue and liver enzyme elevation.
According to a preliminary analysis, 26 of 41 evaluable patients experienced stable disease following combination therapy with MK-1775. This is the first reported clinical evaluation of a Wee1 inhibitor. Larger studies are needed to confirm these results.
MK-1775 is an investigational inhibitor of Wee1, a protein kinase that regulates the cell cycle and DNA repair checkpoints. Inhibiting Wee1 may help to trigger programmed cell death in damaged cancer cells.
A Phase II Study of the Anti-IGFR Antibody MK-0646 in Combination with Cetuximab and Irinotecan in the Treatment of Chemorefractory Metastatic Colorectal Cancer (Abstract # 4127)
Sunday, May 31, 2009, 8:00 a.m. – 12:00 p.m. EDT; Board L6
Data from the safety run-in portion of a Phase II study suggested that the combination of MK-0646, cetuximab and irinotecan in patients with chemo-refractory metastatic colorectal cancer was tolerable with no significant overlapping toxicities.
The initial phase of this study was an open-label, randomized trial designed to assess safety and tolerability of the combination regimen. Patients had previously failed to respond to both irinotecan and oxaliplatin, had progressed on or within three months of their last therapy, and were required to have measurable disease and tissue samples available for tumor KRAS testing. All patients were treated with cetuximab (400 mg/m2 loading dose followed by 250 mg/m2 weekly) and irinotecan according to their previous dosing schedule. Ten patients received 10 mg/kg weekly MK-0646 (Arm A) and eight received a 15 mg/kg loading dose of MK-0646 followed by 7.5 mg/kg every other week (Arm B). The most common grade 3/4 adverse events in Arm A and B were diarrhea (30 percent and 25 percent, respectively), neutropenia (30 percent and 0 percent, respectively) and hyperglycemia (10 percent and 25 percent, respectively).
Preliminary data on tumor response, progression-free survival and response by KRAS status will also be presented. The Phase II portion of the study, which is evaluating the clinical activity of the combination regimen, is ongoing. Larger studies are needed to confirm these results.
MK-0646 is an investigational humanized monoclonal antibody targeting IGF-1R, a tyrosine kinase receptor that promotes proliferation of cancer cells by activating the PI3 kinase signaling cascade. MK-0646 is in Phase II development in collaboration with Pierre Fabre Medicament.
Commitment to Oncology Research
Merck is committed to advancing all aspects of cancer care – prevention, treatment and supportive care. Through strong internal research capabilities, selective alliances and acquisitions, and enabling technologies, Merck is looking to lead in the discovery, development and delivery of targeted anticancer therapies customized for patient subpopulations.
About Merck
Merck & Co., Inc. is a global research-driven pharmaceutical company dedicated to putting patients first. Established in 1891, Merck currently discovers, develops, manufactures and markets vaccines and medicines to address unmet medical needs. The Company devotes extensive efforts to increase access to medicines through far-reaching programs that not only donate its medicines but help deliver them to the people who need them. Merck also publishes unbiased health information as a not-for-profit service. For more information, visit www.merck.com.
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