Oct 1 2012
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.