Exelixis reports preliminary data from cabozantinib phase 1b trial on RCC

Exelixis, Inc. (NASDAQ:EXEL) today reported preliminary data from a cohort of heavily pretreated patients with metastatic refractory renal cell carcinoma (RCC) participating in an ongoing phase 1b trial of cabozantinib. Toni K. Choueiri, M.D., Director of the Kidney Cancer Center at the Dana-Farber Cancer Institute, will present the data (Abstract #364) in a poster session at the 2012 Genitourinary Cancers Symposium at 6:45 a.m. PST tomorrow in San Francisco.

As of the January 18, 2012 data cut-off, 25 RCC patients were enrolled with 88% having received prior anti-VEGF therapy, 60% having received prior mTOR inhibitor therapy, and 52% having received ≥1 anti-VEGF and 1 mTOR therapy. Sixty-four percent of patients received ≥ 2 prior anti-cancer agents. Tumor regression was observed in 19 of 21 patients (90%) with ≥1 post-baseline assessment. Best overall response was determined per RECIST criteria with 7 of 25 patients (28%) showing a confirmed partial response (PR). Importantly, PRs were observed in heavily pretreated patients, including 3 patients with 2-4 prior systemic therapies, and 2 patients with >4 prior systemic therapies. Thirteen additional patients (52%) had stable disease (SD) as their best response, and only a single patient (4%) 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 study and 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 in this 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.

The data presented are from a cohort of 25 RCC patients enrolled in an ongoing phase 1b drug interaction study of cabozantinib in patients with advanced solid tumors. Patients in this trial receive 140 mg of oral cabozantinib administered daily, and the study endpoints are 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 RECIST. Bone metastases were present at baseline in 4 patients (16%), one of whom was followed by bone scan.

"The high rate of durable tumor response, very low rate of primary refractoriness to drug therapy, and the long median progression-free survival observed in these heavily pretreated RCC patients are very encouraging," said Michael M. Morrissey, Ph.D., president and chief executive officer of Exelixis. "Additionally, the bone scan response and reduction in narcotic usage in two of the four patients with bone metastases are consistent with the positive effects that we have observed for cabozantinib with respect to bone lesions in patients with castration-resistant prostate cancer and metastatic breast cancer. The data presented today support continued study of cabozantinib in patients with advanced RCC, and we hope to pursue such studies as part of our recently announced Cooperative Research and Development Agreement with the National Cancer Institute's Cancer Therapy and Evaluation Program."

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%).

"These data indicate that cabozantinib can provide clinical benefit to patients with advanced RCC, including those who have received anti-VEGF therapy, anti-mTOR therapy, or a sequence of these targeted therapies," said Dr. Choueiri. "While anti-VEGF and anti-mTOR therapies have advanced the treatment of RCC, many patients are refractory to these agents and experience disease progression. Dual inhibition of both VEGFR2 and MET by cabozantinib may provide an alternative or additional mechanism for controlling disease in these patients, and further study of cabozantinib in this indication is warranted."


Exelixis, Inc.


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