Press Release
Press Release
Exelixis Reports Positive Preliminary Phase 2 Cabozantinib Data in Patients with Hepatocellular Carcinoma
Data Highlight Progression Free Survival of 4.2 months in both sorafenib-pretreated and -naïve patients
The week 12 disease control rate (PR and SD at week 12) was 68%. Evidence of objective tumor regression was observed in 78% of patients, including those with or without prior sorafenib therapy. The best radiologic response per RECIST in the lead-in stage of the study for 36 patients with at least one post-baseline measurement was confirmed partial response (cPR) in 2 patients and stable disease (SD) in 32 patients. One additional patient had a partial response that was confirmed after the patient completed the lead-in stage and proceeded to the randomized component of the trial. Median progression-free survival (PFS) was 4.2 months, and was similar for sorafenib-pretreated and sorafenib-naïve patients.
The results include data from 41 patients with advanced hepatocellular carcinoma (HCC) with measurable disease at baseline and documented progressive disease per RECIST criteria. Eligible patients had Child-Pugh Score A. Seventy-one percent of patients had one prior line of systemic therapy: 24% had received prior chemotherapy and 56% prior tyrosine kinase inhibitor (TKI) therapy, including 51% previously treated with sorafenib. Extrahepatic spread of disease was present in 70% of subjects, median AFP level was 368 and thrombocytopenia was present in 34%. Patients in the open label 12 week lead-in stage of the trial received a starting dose of 100 mg of oral cabozantinib daily.
A >50% reduction in the tumor marker alpha-fetoprotein (AFP) serum level was observed in 10 (38%) of 26 patients with AFP levels of ≥ 20 ng/mL at baseline and at least one post baseline measurement.
“We are very encouraged by the disease control rates observed in this
population of patients with hepatocellular carcinoma,” said Michael M.
Morrissey, Ph.D., president and chief executive officer of
The tolerability of cabozantinib in patients with HCC was similar to that of other TKIs. The most frequently reported ≥ grade 3 adverse events (AEs), regardless of causality in the 41 patients in the HCC cohort were: diarrhea (17%), palmar-plantar erythrodyesthesia (15%), thrombocytopenia (10%), asthenia (7%), aspartate aminotransferase elevation (5%), and fatigue, nausea, vomiting, hypertension, and weight decrease (2% each).There were no grade 5 events related to cabozantinib.
“These compelling results highlight cabozantinib’s potential clinical utility in HCC,” said Dr. Cohn. “In particular, the anti-tumor activity in patients with and without prior sorafenib therapy suggests that we may see additional benefit for pretreated and treatment-naïve patients through simultaneous inhibition of MET and VEGF signaling, rather than VEGF alone. Further study of cabozantinib in patients with HCC is clearly warranted.”
The clinical data poster mentioned in this press release will be
available at www.exelixis.com
commencing at
Randomized Discontinuation Trial Design
The data above are from the HCC cohort from the randomized discontinuation trial evaluating the activity of cabozantinib in multiple tumor types. In the RDT design, patients initially receive open label cabozantinib at 100 mg daily (free base equivalents, corresponding to 125 mg salt form) during a 12-week Lead-In phase, which evaluates the effects of uninterrupted cabozantinib administration. Patients achieving a PR per RECIST criteria at week 12 are eligible for continued open label treatment with cabozantinib, and patients with progressive disease discontinue treatment. Patients with SD enter the randomized discontinuation phase, which assesses the progression free survival of these patients after random allocation to blinded placebo vs. cabozantinib. Patients progressing on placebo have the option of receiving salvage therapy with cabozantinib.
About Cabozantinib
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. In preclinical studies, cabozantinib has shown powerful tumoricidal, antimetastatic and antiangiogenic effects, including:
- Extensive apoptosis of malignant cells
- Decreased tumor invasiveness and metastasis
- Decreased tumor and endothelial cell proliferation
- Blockade of metastatic bone lesion progression
- Disruption of tumor vasculature
About
Forward-Looking Statements
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 noteworthy and
warrant further study of cabozantinib in patients with HCC; the hope to
study cabozantinib further in HCC; the potential clinical utility of
cabozantinib in HCC; and the suggestion that there may be additional
benefit for pretreated and treatment-naïve patients through simultaneous
inhibition of MET and VEGF signaling, rather than VEGF alone. Words such
as “positive,” “encouraged,” “noteworthy,” “warrant,” “hope,”
“compelling,” “potential,” “suggests,” “may,” “believes,” and similar
expressions are intended to identify forward-looking statements. These
forward-looking statements are based upon
Source:
Exelixis, Inc.
Charles Butler, 650-837-7277
Vice
President,
Investor Relations and
Corporate
Communications
cbutler@exelixis.com