Further analysis of the Phase III CRYSTAL trial once again confirmed the therapeutic value of Erbitux®. New data show that patients with KRAS wild-type metastatic colorectal cancer (mCRC) who experienced early tumor shrinkage during first-line Erbitux®-based treatment had an unprecedented overall median survival of 28.3 months. Further Phase III studies are being conducted in gastric cancer (EXPAND) and adjuvant colorectal cancer (PETACC-8).
Initial results of the randomized Phase II trial BALI-1 demonstrated the therapeutic potential of Erbitux® in breast cancer. Treatment with Erbitux® in combination with chemotherapy showed positive results in patients with metastatic triple-negative breast cancer (TNBC). Median progression-free survival in women treated with Erbitux® plus chemotherapy more than doubled. Although tumor response nearly doubled, the primary endpoint of the study, response rate, was not met. TNBC is aggressive, difficult to treat, and associated with high rates of metastasis and relapse.
Stimuvax®: Clinical program resumed, obstacles successfully overcome
In June, Merck resumed the Stimuvax® (BLP25 liposome vaccine) clinical program in patients with non-small cell lung cancer (NSCLC), which includes the Phase III studies START and INSPIRE. The treatment and enrollment of patients has restarted after approval by the local regulatory authorities and ethics committees. This was made possible by a decision by the U.S. Food and Drug Administration (FDA) to partially lift the clinical hold and allow the START trial to resume. The Phase III STRIDE trial in advanced breast cancer was the study that remained on clinical hold by the FDA. Merck Serono decided to close this study.
The clinical hold was put in place by the FDA in March 2010 following a suspected unexpected serious adverse reaction. A patient participating in a Phase II exploratory clinical trial with the cancer immunotherapy in multiple myeloma developed encephalitis. Since 2007, we have been conducting the START trial to evaluate the efficacy and safety of the treatment with Stimuvax® in patients with inoperable stage III non-small cell lung cancer. The decision to initiate this trial was based on the results of a randomized Phase IIb study, in which Stimuvax® showed an increase in overall survival of a subset of patients with locoregional stage IIIb NSCLC from 13.3 months in the control group to 30.6 months in the treatment group. In 2009, we initiated INSPIRE, a Phase III trial in NSCLC in Asia. Should the Phase III trials be successfully completed, this cancer immunotherapy could play an important role in the treatment of lung cancer patients, for whom current therapeutic options are still limited.
Cilengitide trial provides long-term follow-up data in glioblastoma patients
Cilengitide is the first integrin inhibitor in oncology to have entered Phase III clinical development. In the CENTRIC trial, we are studying this compound in glioblastoma (GBM), the most aggressive type of brain tumor. Integrin inhibitors are thought to work by targeting tumor cells and the vascular network required to nourish the tumor and promote cancer cell growth. Long-term follow-up data from a randomized Phase II study of two different cilengitide doses in recurrent glioblastoma were published in 2010. They showed that 37% of patients who received the higher dose of cilengitide (2000 mg) were still alive after one year. The current prognosis of patients with recurrent glioblastoma is poor with median overall survival between four and seven months and one-year survival rates of approximately 20%.
Pipeline: All resources focused on promising projects
Merck Serono remains committed to its discovery and development work in the therapeutic area of oncology. Our aim is to offer patients with high unmet medical needs additional therapeutic options in various indications. An important step toward this aim is the worldwide research and development agreement entered into with Sanofi-Aventis at the end of 2010. This agreement allows the experimental combination of Merck’s MEK inhibitor with one of two early compounds of the partner, respectively.
We are currently investigating three compounds in Phase I studies in solid tumors and hematological diseases. In addition, five Phase II studies are underway in breast, head and neck, non-small cell lung as well as colorectal cancer.
Since our pipeline includes numerous compounds with high therapeutic potential, we remain committed to moving forward those projects with the greatest promise of sustainable success. At the same time, we will terminate or divest at an early stage those projects that appear to be less promising. This enables us to ensure that our resources are deployed to benefit patients and to manage the risks for our company. In 2010, we terminated the following four early-stage oncology projects: an aurora-kinase inhibitor and the monoclonal antibody sonepcizumab in Phase I; the immunocytokine tucotuzomab celmoleukin and the monoclonal antibody adecatumumab in Phase II.
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