Exelix reports preliminary data from cabozantinib phase 1 study on solid tumors

Exelixis, Inc. (NASDAQ:EXEL) today reported preliminary data from an ongoing phase 1 dose escalation study of cabozantinib in Japan. Hiroshi Nokihara, M.D., Ph.D., a physician at the National Cancer Center Hospital in Tokyo, Japan, and an investigator on the trial, presented the data today in a poster discussion session at the European Society for Medical Oncology 2012 Annual Meeting (Abstract #1708PD) in Vienna, Austria.    

The primary objective of the phase 1, open label, multiple cohort dose escalation study is to determine the recommended phase 2 dose of cabozantinib administered once-daily over a 4-week cycle in Japanese patients with advanced or metastatic solid tumors. Doses evaluated were 40 mg, 60 mg, or 80 mg of cabozantinib in the capsule configuration. Secondary objectives are to assess the safety and tolerability of multiple doses of cabozantinib, plasma pharmacokinetics, and tumor response.

As of the June 30, 2012 cut-off, 14 patients with a variety of solid tumors had been enrolled in the study: non-small cell lung cancer (NSCLC) (5), gastrointestinal stromal tumor (4), colorectal cancer (2), medullary thyroid cancer (1), thymic cancer (1), and leiomyosarcoma (1). The median number of prior treatments was 3 (range: 2-6) for all 14 patients, and 4 (range: 2-6) for the NSCLC subgroup. Dose-limiting toxicity of Grade 3 hypertension was reported in 2 patients, and the recommended phase 2 dose is 60 mg daily. Pharmacokinetic analyses show that cabozantinib exhibited dose-linear increases in exposure over the range of doses evaluated, and a 5- to 6-fold accumulation was observed on Day 19 following repeated daily dosing. These analyses also show that cabozantinib exposure in Japanese patients is approximately 2-fold higher than that observed in non-Japanese patients.

Of the 14 patients, 4 had confirmed partial responses (cPR) as their best tumor response, 8 had stable disease of at least 12 weeks, and 2 had progressive disease. Eleven of the 14 patients had decreases in tumor size compared with baseline. The 4 cPRs were observed in the NSCLC subgroup of 5 patients. All 5 NSCLC patients had tumor regression ranging from 33% to 41%. All 4 patients with a cPR had mutations or translocations involving either EGFR, RET, or ALK, while the NSCLC patient with a best response of stable disease had no mutations in these genes or in KRAS. Treatment duration for the NSCLC subgroup ranged from 4 to 15+ months. Five patients remained on study as of the June 30, 2012 cut-off.

The most common adverse events (AEs) of grade 3 or higher, regardless of causality, were: hypertension (3 patients), neutropenia (2), palmar plantar erythrodyesthesia (1), lipase increased (1), GGT increased (1), and lymphopenia (1). Five serious AEs have been reported in 3 patients, including anemia, hematemesis, intestinal obstruction, melena (all related to cabozantinib), and pleural effusion (unrelated to cabozantinib).

"The data from this phase 1 study in Japanese patients provide an initial signal of anti-tumor activity at generally well-tolerated doses of cabozantinib," said Michael M. Morrissey, Ph.D., president and chief executive officer of Exelixis. "We intend to further explore the potential of cabozantinib in selected patient populations with specific mutations commonly found in Japanese NSCLC patients."     

Source: Exelixis, Inc.