14.7 months median progression free survival
28% confirmed partial response rate & 72% disease control rate at week 16
As of the
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
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.”
The clinical data poster mentioned in this press release will be
available at www.exelixis.com
Cabozantinib is a potent, dual inhibitor of MET and VEGFR2. Cabozantinib is an investigational agent that provides coordinated inhibition of metastasis and angiogenesis to kill tumor cells while blocking their escape pathways. The therapeutic role of cabozantinib is currently being investigated across several tumor types. MET is upregulated in many tumor types, thus facilitating tumor cell escape by promoting the formation of more aggressive phenotypes, resulting in metastasis. MET-driven metastasis may be further stimulated by hypoxic conditions in the tumor environment, which are often exacerbated by selective VEGF-pathway inhibitors. The vast majority of RCC cases have an inactivation of the von Hippel-Lindau tumor suppressor gene, which mimics a hypoxic state and triggers upregulation of both VEGF and MET expression. In preclinical studies, cabozantinib has shown powerful tumoricidal, antimetastatic and antiangiogenic effects, including:
This press release contains forward-looking statements, including, without limitation, statements related to: the continued development and clinical, therapeutic and commercial potential of, and opportunities for, cabozantinib; the belief that the referenced data is encouraging and warrant further study of cabozantinib in patients with RCC; the hope to study cabozantinib further in RCC; the potential clinical utility of cabozantinib in RCC; the belief that cabozantinib can provide clinical belief to patients with advanced RCC; and the belief that dual inhibition of both VEGFR2 and MET by cabozantinib may provide an alternative or additional mechanism for controlling disease in RCC patients.
Words such as “encouraging,” “support,” “hope,” “indicate,” “can,”
“may,” “warranted,” “believes,” “potential,” and similar expressions are
intended to identify forward-looking statements. These forward-looking
statements are based upon
Charles Butler, 650-837-7277
Investor Relations and