Press Release
Press Release
Exelixis Reports Encouraging Phase 1 Data for the PI3K Inhibitor XL147 (SAR245408) in Combination with Paclitaxel and Carboplatin at the AACR-NCI-EORTC Conference
“Preclinical data suggest that XL147 potentiates the antitumor efficacy
of paclitaxel and carboplatin without exacerbating the toxicity of this
commonly used regimen,” said
The study is evaluating escalating doses of XL147 administered daily for a 21-day cycle in combination with paclitaxel and carboplatin administered intravenously on Day 1 of the cycle. In Part A of the study, paclitaxel and carboplatin will be dose-escalated up to 175 mg/m2 and AUC 6, respectively, with expansion at the maximum tolerated dose (MTD) in patients with endometrial and ovarian cancer. In Part B, paclitaxel and carboplatin will be dose-escalated up to 225 mg/m2 and AUC 6, respectively, with expansion at the MTD in patients with non-small cell lung cancer (NSCLC).
As of
As of
Preliminary pharmacokinetic (PK) analyses indicate that the PK profiles of XL147, paclitaxel, and carboplatin administered in combination are similar to the PK profiles of each compound administered as a single agent. Robust pharmacodynamic modulation of the PI3K pathway was evident in tumor biopsies at plasma exposures consistent with those associated with PI3K inhibition in tumors in an ongoing single-agent phase 1 trial of XL147. The patient with cervical adenocarcinoma, who experienced a PR, had biomarker reductions ranging from 69% to 76%, and a patient with colon cancer had reductions ranging from 64% to 73%.
Fifteen patients were available for safety assessments. There have been no dose-limiting toxicities. One patient experienced a serious adverse event (Grade 4 thrombocytopenia), which was considered related to study treatment. The event resolved and study treatment was resumed without recurrence. Five patients had a dose reduction of carboplatin and/or paclitaxel; no dose reductions of XL147 were reported. Treatment-related adverse events occurring in at least 20% of patients were neutropenia (53%), fatigue (53%), anemia (47%), thrombocytopenia (47%), nausea (33%), diarrhea, peripheral neuropathy and rash (each 27%) and alopecia, anorexia and vomiting (each 20%).
To access the clinical data poster mentioned in this press release, please visit www.exelixis.com.
About XL147
XL147 selectively targets PI3K. Upregulation of PI3K activity is one of
the most common characteristics of human tumor cells and can result from
activation of growth factor receptors, mutational activation or
amplification of the PI3K gene, downregulation of the PTEN lipid
phosphatase, or activating mutations in RAS. Activation of PI3K results
in stimulation of AKT and mTOR kinases, resulting in promotion of tumor
cell proliferation and survival. This survival signal plays a
significant role in conferring resistance to chemotherapy and
radiotherapy by inhibiting apoptotic cell death. In preclinical cancer
models, administration of XL147 leads to tumor growth inhibition or
regression and has been shown to enhance the activity of EGFR-targeted
agents and cytotoxic drugs.
About
Exelixis Forward-Looking Statements
This press release contains forward-looking statements, including,
without limitation, statements related to data that suggests that XL147
potentiates the antitumor efficacy of paclitaxel and carboplatin without
exacerbating the toxicity of the commonly used regimen; emerging signs
of clinical activity and good tolerability of the
XL147/paclitaxel/carboplatin combination; the potential for enhancing
anti-tumor activity by combining XL147 with two of the most commonly
used chemotherapy agents; and dose-escalation plans for the XL147 study
in combination with paclitaxel and carboplatin. Words such as “suggest,”
“emerging,” “demonstrate,” “potential,” “will,” and similar expressions
are intended to identify forward-looking statements. These
forward-looking statements are based upon Exelixis’ current plans,
assumptions, beliefs and expectations. Forward-looking statements
involve risks and uncertainties. Exelixis’ actual results and the timing
of events could differ materially from those anticipated in such
forward-looking statements as a result of these risks and uncertainties,
which include, without limitation, risks related to the potential
failure of XL147 to demonstrate safety and efficacy in clinical testing
and Exelixis’ ability to conduct clinical trials of XL147 sufficient to
achieve a positive completion. These and other risk factors are
discussed under “Risk Factors” and elsewhere in Exelixis’ quarterly
report on Form 10-Q for the quarter ended
Source:
Exelixis, Inc.
Charles Butler, 650-837-7277
Vice President,
Corporate Communications & Investor Relations
cbutler@exelixis.com