Press Release
| Cabozantinib Demonstrates Evidence of Anti-Tumor Effects in Heavily Pretreated Patients with Hepatocellular Carcinoma |
Data Show High Rates of Objective Tumor Regression, AFP Response and Encouraging Progression-Free and Overall Survival The results comprise data from 41 patients with advanced hepatocellular carcinoma with measurable disease at baseline and documented progressive disease per RECIST criteria. Patients in the open label 12-week Lead-In Stage of the trial received a daily dose of 100 mg cabozantinib. Eligible patients had Child-Pugh Score A. Eighty percent had received 1-2 prior lines of systemic therapy: 56% had prior tyrosine kinase inhibitor (TKI) therapy, including 51% previously treated with sorafenib. At baseline, extrahepatic spread of disease (which is associated with a poorer prognosis) was present in 73% of subjects, 39% had hemoglobin (Hb) < 11 g/dL, 34% had thrombocytopenia, and median alpha-fetoprotein (AFP) level was 368 ng/ml. Tumor assessments per original RECIST 1.0 were conducted using conventional CT/MRI at baseline and every 6 weeks thereafter. Progression-Free survival (PFS) and Overall Survival (OS). Median PFS was 4.4 months, and was similar for sorafenib-pretreated and sorafenib-naïve patients. Median OS in the 41 patients was 15.1 months. Response Rate. The week 12 disease control rate (partial response [PR] and stable disease [SD] at week 12) was 66%. 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 PR in 2 patients (5%) and SD in 32 patients (78%).
“The progression-free survival and overall survival results observed to
date are encouraging,” said Eric Van Cutsem, M.D., Ph.D., professor of
internal medicine and digestive oncology at the University Hospitals
Gasthuisberg, Leuven, AFP Biomarker and hemoglobin. A decrease of >50% in serum AFP was observed in 9 of 26 patients (35%) with baseline values ≥ 20 ng/mL The median maximum rise in Hb for the 13 patients with baseline Hb < 11 g/dL was 3.1 g/dL (range 1.3 to 7.8 g/dL).
“These interim data are encouraging and support the potential utility of
cabozantinib in the treatment of HCC,” said Safety Results The tolerability of cabozantinib in patients with HCC was similar to that of other TKIs. The most frequently reported adverse events (AEs) of grade ≥ 3, regardless of causality in the 41 patients in the HCC cohort were: diarrhea (20%), hand-foot syndrome (15%), thrombocytopenia (15%), aspartate aminotransferase increased (10%), asthenia (7%), hypertension (7%), fatigue (10%), nausea (2%), vomiting (2%), and weight decreased (2%). There were no grade 5 events related to cabozantinib and no clinically significant bleeding was reported. Randomized Discontinuation Trial Design The presented 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 Stage, 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 randomization and blinded allocation to placebo vs. cabozantinib. Patients progressing on placebo have the option of receiving salvage therapy with cabozantinib. About Cabozantinib Cabozantinib is a potent targeted therapy that inhibits 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:
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 are encouraging
and suggest that dual inhibition of MET and VEGF with cabozantinib may
provide clinical benefit beyond what can be achieved through inhibition
of either pathway alone; the potential utility of cabozantinib in the
treatment of HCC; and the referenced planned randomized phase 2 trial of
cabozantinib in HCC and the expected benefits of such planned trial.
Words such as “demonstrates,” “positive,” “encouraging,” “suggest,”
“may,” “can,” “support,” “planned,” “believe,” “will” “potential,” and
similar expressions are intended to identify forward-looking statements.
These forward-looking statements are based upon Source:
Exelixis, Inc.
|