6/3/2012 2:33 AM ET
(RTTNews) - Biotechnology company Exelixis, Inc. (EXEL: News), revealed positive updated interim data from an ongoing phase 1b trial of cabozantinib in patients with metastatic refractory renal cell carcinoma.

The study endpoints included safety, tolerability, and anti-tumor activity. The data presented are from a cohort of 25 renal cell carcinoma patients enrolled in the phase 1b drug-drug interaction study of cabozantinib at the phase 1 maximum tolerated dose in patients with advanced solid tumors.

All patients had histologically confirmed renal cell carcinoma - with clear cell components - and metastases, were refractory to or had progressed following standard therapy, and had measurable disease per RECIST. Subjects in the trial were administered 140 mg of oral cabozantinib daily and a single dose of rosiglitazone at day 22.

Exelixis indicated the clinical benefit observed with cabozantinib as encouraging, particularly in highly pretreated patients who are refractory to anti-VEGF and anti-mTOR therapies or who have had disease progression while on these agents. Improvements in bone lesions and bone pain were also indicated as encouraging, especially given that bone metastases occur in up to 30 percent of renal cell carcinoma patients.

Objectively, tumor regression was observed in 19 of 21 patients, or 90 percent. Best overall response was determined per RECIST criteria with 7 of 25 patients, or 28 percent, showing a confirmed partial response.

Thirteen additional patients, or 52 percent, had stable disease as their best response, and only a single patient demonstrated evidence of primary refractoriness to cabozantinib with a best overall response of progressive disease. The rate of disease control at week 16 for all 25 patients is 72%.

Kaplan Meier estimate of median progression-free survival was 14.7 months. Median overall survival had not yet been reached after median follow-up of 14.7 months. The estimated 1-year survival rate was 60 percent. Seven patients remain on study and progression free with treatment durations ranging up to 21.8+ months.

Safety results for the study were consistent with those observed in other trials of cabozantinib and with other tyrosine kinase inhibitor therapies. The most frequently reported adverse events were hypophosphatemia, hyponatremia, fatigue, diarrhea, proteinuria, decreased appetite, vomiting, and hand-foot syndrome. Grade 3 and higher adverse events included hypertension in 8% of patients.

Dr. Michael Morrissey, president and chief executive officer of Exelixis, observed, "Taken together, the data demonstrate cabozantinib's potential role to improve care and outcomes for patients with RCC. A randomized phase 2 trial in first-line RCC using a 60 mg dose is planned under our Cooperative Research and Development Agreement with the National Cancer Institute's Cancer Therapy Evaluation Program and should provide further insight into cabozantinib's clinical and commercial potential in this indication."

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