Curis, Inc. (NASDAQ: CRIS), a drug development company seeking to develop next generation targeted small molecule drug candidates for cancer treatment, today announced that it has received preliminary results from a Phase II clinical trial of GDC-0449 from Roche and Genentech, Curis' collaborator and a member of the Roche Group. GDC-0449, a first-in-class Hedgehog pathway inhibitor, was tested by Roche and Genentech as a single agent maintenance therapy for ovarian cancer patients in their second or third complete remission from the disease. Roche has informed Curis that preliminary findings from the primary analysis of the study warrant additional investigation to clarify and interpret potential clinical activity of the drug candidate observed in this trial. Accordingly, Roche and Genentech have indicated that they plan to further analyze the data, including subset analyses in the coming months. Following these analyses, they expect to make a portfolio decision regarding whether, or to what extent, they will continue development of GDC-0449 in advanced ovarian cancer.
“While we await the final analysis of the data from this advanced ovarian cancer study, we remain optimistic about the continued evaluation of GDC-0449 in tumors such as basal cell carcinoma”
No obvious new safety signals were observed in patients treated with GDC-0449. It is expected that data from this Phase II study will be submitted for presentation at an upcoming medical meeting.
"While we await the final analysis of the data from this advanced ovarian cancer study, we remain optimistic about the continued evaluation of GDC-0449 in tumors such as basal cell carcinoma," said Dan Passeri, Curis' President and Chief Executive Officer. "Genentech and Roche have completed enrollment in a pivotal Phase II trial in advanced basal cell carcinoma, a use for which proof of concept has already been demonstrated in a Phase I clinical study. In addition, Roche has indicated that it expects to initiate a Phase II clinical trial in operable basal cell carcinoma patients during the second half of 2010 which we believe, assuming positive data, could expand the commercial opportunity of GDC-0449 in basal cell carcinoma."
Mr. Passeri added, "We are also optimistic that the breadth of additional clinical studies of GDC-0449 that are being conducted by the National Cancer Institute (NCI) under a collaborative relationship with Genentech, including studies in Hedgehog mutation-based mechanisms-of-action cancers such as medulloblastoma and basal cell nevus (Gorlin) syndrome as well as in tumors that are believed to utilize the Hedgehog pathway in other ways to support their growth including pancreatic, small cell lung, breast, stomach and esophageal cancers and in glioblastoma and sarcoma. We are hopeful that data from these planned and ongoing studies will provide important information that may help to guide future GDC-0449 development decisions."
Genentech initiated the advanced ovarian cancer trial in December 2008 and completed enrollment in the fourth quarter of 2009. Genentech designed this Phase II clinical trial to investigate whether GDC-0449 might help to delay and/or attenuate tumor re-growth in a maintenance setting following clinical remission of cancer after second-line chemotherapy treatment for recurrent disease. GDC-0449 was evaluated in this study as a single agent maintenance therapy tested in 104 patients with ovarian cancer in second or third complete remission in a randomized, placebo-controlled, double-blind, multi-center Phase II clinical trial. Patients were randomized in a 1:1 ratio to receive either a 150 mg daily dose of GDC-0449 or placebo and were stratified based on whether their cancer was in a second or third complete remission. The primary endpoint of the trial was progression-free survival. Secondary outcome measures included overall survival, measurement of Hedgehog ligand expression in archival tissue and number and attribution of adverse events.
In addition to this Phase II ovarian study evaluating GDC-0449, Genentech and Roche have completed enrollment in a pivotal Phase II trial in advanced basal cell carcinoma. Results from an earlier Phase I clinical trial demonstrated a 55% response rate in 33 advanced BCC patients. GDC-0449 was well tolerated in this Phase I study, with the most frequent adverse events including muscle spasms, altered taste, weight loss and hyponatremia. Roche has indicated that it expects data from the pivotal Phase II study in 2011 and, assuming positive results, that it could also submit regulatory approval applications in 2011.