BASEL, Switzerland — Roche announced this week that a pivotal Phase II clinical study of its investigational Hedgehog Pathway Inhibitor, vismodegib, showed positive results in people with advanced basal cell carcinoma (aBCC), a particularly severe and debilitating form of skin cancer.
The study met its primary endpoint (overall response rate) of showing vismodegib shrank tumors in a pre-defined percentage of people in the study.
A preliminary safety assessment showed the most common adverse events were consistent with previous experience with vismodegib. A detailed safety assessment is ongoing.
“These results are important because people with this disfiguring and potentially life-threatening advanced form of skin cancer currently have no approved treatment options,” said Dr. Hal Barron, chief medical officer and head of Global Product Development.
“We look forward to presenting the study data in more detail and discussing the results with global health authorities,” Barron said.
Data from the study will be submitted for presentation to a future medical meeting.
The Hedgehog signaling pathway plays an important role in regulating proper growth and development in the early stages of life and then becomes less active in adults.
However, mutations in the pathway that reactivate Hedgehog signaling are seen in several different types of cancer.
Abnormal signaling in the Hedgehog pathway is implicated in the majority of basal cell carcinoma (BCC) cases.
Roche is also evaluating vismodegib in a Phase II trial in people with operable forms of BCC, which opened in October 2010.
The clinical trial is an international, single-arm, multi-center two-cohort, open-label Phase II study that enrolled 104 patients with aBCC, including locally advanced and/or metastatic BCC, defined as patients whose lesions are not appropriate for surgery, or for whom surgery would result in substantial deformity.
The primary endpoint of the study was overall response rate (tumor shrinkage), as assessed by independent reviewers.
Secondary endpoints of the study included overall response rate as assessed by study investigators, duration of response, progression-free survival, overall survival and the safety profile.
A preliminary safety assessment showed the most common adverse events were muscle spasms, hair loss, altered taste sensation, with loss, fatigue, nausea, decreased appetite and diarrhea.
Serious adverse events were seen including fatal events. The deaths are being further evaluated but do not appear to be related to vismodegib.
Basal cell carcinoma (BCC) is the most common type of skin cancer in Europe, Australia, and the United States. The annual global incidence is around two million cases worldwide.
The disease is generally considered curable when the cancer is restricted to a small area of the skin. However, in small group of people, if the disease is left untreated or does not respond to treatment, the cancer may advance further into the skin, bones or other tissues.
In a small proportion of patients (estimated at less than four percent), BCC can advance or spread to other parts of the body and can become difficult to treat or becomes a life threatening.