Exelixis Inc. reported preliminary data from pre-treated patients with metastatic refractory renal cell carcinoma (RCC) participating in an ongoing Phase 1b trial of cabozantinib, a potent, dual inhibitor of MET and VEGFR2 that provides coordinated inhibition of metastasis and angiogenesis to kill tumor cells while blocking their escape pathways.

The data presented are from 25 RCC patients enrolled in an ongoing Phase 1b drug interaction study of cabozantinib in patients with advanced solid tumors.

Patients in the trial received 140 mg of oral cabozantinib administered daily, and the study endpoints were safety, tolerability, and anti-tumor activity. The RCC patients had histologically confirmed RCC (with clear cell components) and metastases, were refractory to or had progressed following standard therapy, and had measurable disease per Response Evaluation Criteria In Solid Tumors (RECIST) Bone metastases were present at baseline in 4 patients, one of whom was followed by bone scan.

Enrolled patients consisted of 88% having received prior anti-VEGF therapy, 60% having received prior mTOR inhibitor therapy, and 52% having received more than1 anti-VEGF and 1 mTOR therapy. Sixty-four percent of patients received more than 2 prior anti-cancer agents. Tumor regression was observed in 19 patients with more than 1 post-baseline assessment. The best overall response was determined by RECIST criteria with 7 of 25 patients showing a confirmed partial response (PR). PRs were observed in heavily pretreated patients, including 3 patients with 2 to 4 prior systemic therapies, and 2 patients with more than 4 prior systemic therapies. Thirteen additional patients had stable disease as their best response, and only one patient demonstrated evidence of primary refractoriness to cabozantinib with a best overall response of progressive disease. The rate of disease control (PR + SD) at week 16 for all 25 patients is 72%. Kaplan Meier estimate of median progression-free survival is 14.7 months (95% CI, lower limit 7.3 months—upper limit not reached). Ten patients remain on the study and are progression-free with treatment durations ranging up to 16.4 months.

One patient with symptomatic bone metastases was followed by bone scan. A partial bone scan resolution was observed at week 7 for the patient who had previously been treated with sorafenib, sunitinib, and everolimus. The patient also substantially reduced narcotic use by week 7 and continued on reduced narcotics until week 25. A second patient with bone metastases and bone pain at baseline reported complete resolution of pain by week 4 and remains pain free at week 73.

No new safety signals were observed. The most frequently reported grade ? 3 adverse events (AEs), regardless of causality were: hypophosphatemia (36%), hyponatremia (20%), both manageable with substitution with or without cabozantinib dose reduction or interruption, fatigue (16%), diarrhea (12%), proteinuria (8%), palmar-plantar erythrodyesthesia (4%), and vomiting (4%).

Release Date: Feb. 3, 2012
Source: Exelixis Inc.