SOUTH SAN FRANCISCO, CA USA (Press Release) - December 2, 2013 - (Business Wire) Exelixis, Inc. today announced that it has initiated a phase 2 clinical trial comparing cabozantinib plus abiraterone and prednisone (abiraterone/prednisone) versus abiraterone/prednisone in patients with castration-resistant prostate cancer (CRPC) who have bone metastases and have not been previously treated with chemotherapy. The primary endpoint for the randomized, open-label trial is radiographic progression-free survival (PFS).
“A growing body of data support the potential clinical utility of cabozantinib in treating patients with metastatic CRPC,” said Christopher Sweeney, MBBS, clinical director, genitourinary oncology at the Dana-Farber Cancer Institute in Boston, and the lead investigator on the phase 2 trial. “Phase 1 experience from our institution provided important insight into clinical activity when cabozantinib is administered in combination with full dose abiraterone in this patient population, opening the door to potential new treatment options for CRPC patients who have bone metastases but have not yet received chemotherapy. Continued study of cabozantinib in a variety of CRPC indications may help to advance the treatment of the disease.”
The phase 2 trial will compare abiraterone/prednisone against abiraterone/prednisone in combination with one of the three cabozantinib doses: 40 mg daily, 20 mg daily, or 20 mg every other day. The trial is expected to enroll 280 chemotherapy-naïve CRPC patients who have bone metastases, and will be conducted at approximately 50 sites in North America. In addition to evaluating radiographic PFS, the trial includes pre-specified outcome measures of safety and tolerability, pharmacokinetics of cabozantinib in combination with abiraterone, overall survival (OS), and bone scan response by computer-aided detection.
“With its differentiated mechanism targeting MET, RET, and VEGFR2, we believe cabozantinib has the potential to be therapeutically complementary with prostate cancer therapies such as abiraterone and enzalutamide,” said Michael M. Morrissey, Ph.D., president and chief executive officer of Exelixis. “We believe that the results of this trial will provide important insight into the role that cabozantinib might play in earlier lines of therapy, including patients who have not yet received chemotherapy. This trial, and our planned phase 1 trial of cabozantinib in combination with enzalutamide, which is expected to start in the first half of 2014, should support our efforts to realize the full clinical and commercial potential of cabozantinib in CRPC.”
About Cabozantinib
Cabozantinib inhibits the activity of tyrosine kinases including MET, RET and VEGFR2. These receptor tyrosine kinases are involved in both normal cellular function and in pathologic processes such as oncogenesis, metastasis, tumor angiogenesis, and maintenance of the tumor microenvironment. COMETRIQ® (cabozantinib) is currently approved by the U.S. Food and Drug Administration for the treatment of progressive, metastatic medullary thyroid cancer.
WARNING: PERFORATIONS AND FISTULAS, and HEMORRHAGE
- Serious and sometimes fatal gastrointestinal perforations and fistulas occur in COMETRIQ-treated patients.
- Severe and sometimes fatal hemorrhage occurs in COMETRIQ-treated patients.
- COMETRIQ treatment results in an increase in thrombotic events, such as heart attacks.
- Wound complications have been reported with COMETRIQ.
- COMETRIQ treatment results in an increase in hypertension.
- Osteonecrosis of the jaw has been observed in COMETRIQ-treated patients.
- Palmar-Plantar Erythrodysesthesia (PPE) Syndrome occurs in patients treated with COMETRIQ.
- The kidneys can be adversely affected by COMETRIQ. Proteinuria and nephrotic syndrome have been reported in patients receiving COMETRIQ.
- Reversible Posterior Leukoencephalopathy Syndrome has been observed with COMETRIQ.
- COMETRIQ is not recommended for use in patients with moderate or severe hepatic impairment.
- COMETRIQ can cause fetal harm when administered to a pregnant woman.
Adverse Reactions – The most commonly reported adverse drug reactions (≥25%) are diarrhea, stomatitis, palmar-plantar erythrodysesthesia syndrome (PPES), decreased weight, decreased appetite, nausea, fatigue, oral pain, hair color changes, dysgeusia, hypertension, abdominal pain, and constipation. The most common laboratory abnormalities (≥25%) are increased AST, increased ALT, lymphopenia, increased alkaline phosphatase, hypocalcemia, neutropenia, thrombocytopenia, hypophosphatemia, and hyperbilirubinemia.
Drug Interactions – COMETRIQ is a CYP3A4 substrate. Co-administration of strong CYP3A4 inhibitors can increase cabozantinib exposure. Chronic co-administration of strong CYP3A4 inducers can reduce cabozantinib exposure.
For full prescribing information, including Boxed Warning, please visit www.COMETRIQ.com.
About Exelixis
Exelixis, Inc. is a biotechnology company committed to developing small molecule therapies for the treatment of cancer. Exelixis is focusing its proprietary resources and development efforts exclusively on COMETRIQ® (cabozantinib). Exelixis has also established a portfolio of other novel compounds that it believes have the potential to address serious unmet medical needs, many of which are being advanced by partners as part of collaborations. For more information, please visit the company's web site at www.exelixis.com.
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