Ariad Pharmaceuticals, Inc. announced interim results of a randomized, open-label, active-control multi-centre phase 2 study of oral ridaforolimus, an investigational mTOR inhibitor, in patients with metastatic or recurrent endometrial cancer. Based on this interim analysis, the study demonstrated a statistically significant improvement in the primary endpoint of median progression-free survival (PFS) in patients receiving single-agent ridaforolimus compared to patients receiving standard-of-care treatment. The data were presented Saturday in the Plenary Session of the 13th Biennial Meeting of the International Gynecologic Cancer Society being held in Prague, Czech Republic. Ridaforolimus is currently being developed by Merck in multiple cancer indications under an exclusive license and collaboration agreement with Ariad.
"We are very encouraged by the data with oral ridaforolimus, which for the first time demonstrated improvement in PFS in patients with advanced endometrial cancer receiving a targeted therapy in a well-controlled clinical trial," stated Amit Oza, M.D., professor of medicine at the Princess Margaret Hospital, Toronto, Ontario, Canada. "These results support a previous non-randomized study of ridaforolimus in the same patient population."
The interim analysis was based on 114 patients enrolled at 39 sites in North America and Europe. Patients in the trial were randomized to receive either oral ridaforolimus (n=57), or oral progestin (n=48) or chemotherapy (n=9), both standard treatments in patients with advanced endometrial cancer. PFS was determined using RECIST (Response Evaluation Criteria In Solid Tumours) criteria based on radiologic studies conducted every two months. An independent review committee evaluated all of the radiologic studies for determination of PFS. The interim analysis demonstrated a significant improvement in the study's primary endpoint, PFS, with a statistically significant 1.7 month difference in median PFS (ridaforolimus, 3.6 months; standard of care, 1.9 months, p=0.007) and a hazard ratio of 0.52.
The interim analysis also showed that the most common adverse events observed with ridaforolimus were mucositis (38.2%), stomatitis (21.8%) and hyperglycaemia (27.3%), which have been observed in previous studies and are considered to be class effects of mTOR inhibitors. Overall, patients treated with ridaforolimus had significantly more serious adverse events (23.6%) than patients treated with the standard of care (3.8%).
"Based on these data indicating a statistically significant improvement in the trial's primary endpoint of PFS, Merck has stopped further enrolment in the trial, while continuing to follow surviving patients," said Eric Rubin, M.D., vice president, Oncology, Merck Research Laboratories.
Ridaforolimus is a targeted and potent small-molecule inhibitor of the protein mTOR. mTOR acts as a central regulator of protein synthesis, cell proliferation, cell cycle progression and cell survival, integrating signals from proteins such as PI3K, AKT and PTEN known to be important to malignancy.
Endometrial cancer, which develops from the inner lining of the uterus, is the most common cancer found in the female reproductive system. Prognosis for patients is primarily based on the time of diagnosis relative to the stage of the cancer. Initial treatment consists of surgery alone, or in combination with radiation, chemotherapy and/or hormonal therapy. For those women with disease progression, chemotherapy is the only currently available treatment option, and limited benefit has been seen in such cases, emphasizing the need for new therapies.
Ariad's vision is to transform the lives of cancer patients with breakthrough medicines. The Company's mission is to discover, develop and commercialize small-molecule drugs to treat cancer in patients with the greatest and most urgent unmet medical need - aggressive cancers where current therapies are inadequate.