Updated data on XL184 study in patients with glioblastoma multiforme presented

Exelixis, Inc. (Nasdaq:EXEL) and Bristol-Myers Squibb Company (NYSE:BMY) today reported updated phase 2 clinical data which show that XL184 demonstrated activity in patients with glioblastoma multiforme (GBM), the most common and aggressive form of brain cancer.

The data from study XL184-201 were presented today during a poster session at the 2009 Joint Meeting of the Society for Neuro-Oncology and the AANS/CNS Section on Tumors.

The study evaluates the safety, tolerability, and clinical activity of XL184 at continuous daily doses of 175 mg or 125 mg in patients with previously treated GBM, including some patients who had received prior antiangiogenic therapy. A total of 46 patients in first or second relapse were enrolled and dosed with 175 mg of XL184 administered daily, and enrollment at this dose level is complete. Due to frequent dose interruptions and reductions, the study was amended earlier this year to initiate a new cohort of patients receiving 125mg. As of October 12, 2009, 38 patients have been enrolled at the 125 mg dose level with 18 patients with at least one IRF read post baseline scan.

Tumor response was determined by an independent and blinded radiology facility (IRF) per modified MacDonald criteria. As of September 25, 2009, the overall rate of confirmed partial response in the intent-to-treat population of all patients treated at 175 mg was 8/46 (17%). Among patients without prior antiangiogenic therapy, 7 of 34 (21%) achieved confirmed responses. In patients who had received prior antiangiogenic therapy, 1 of 12 (8%), a patient who had progressed on vandetinib, achieved a confirmed partial response. Of the 46 patients treated at the 175 mg dose level, 21% attained 6-month progression-free survival (PFS) rate with 16/46 (35%) patients censored for PFS at the time of analysis. The median duration of response was 5.9 months. The median PFS interval was 3.7 months.

Follow up for the patients receiving 125 mg is relatively short, with the first patient enrolled in late June 2009. Of the 38 patients enrolled at the 125 mg dose level as of October 12, 2009, 18 patients had at least one post-baseline scan available that had undergone IRF evaluation. Of these 18 patients, 7 have discontinued treatment -- 4 due to progressive disease/clinical deterioration per investigator and 3 due to adverse events. Of 14 antiangiogenic naïve patients enrolled at this dose level, eight have had tumor shrinkage of more than 50% as determined by IRF, including two confirmed partial responses by IRF.

The safety experience, to date, is primarily derived from the 175 mg dose level. The most frequently occurring Grade 3 and Grade 4 adverse events (>5%) regardless of relationship to drug were: fatigue, headache, palmar-plantar erythrodysesthesia, confusional state, alanine aminotransferase increase, convulsion, lymphopenia, hypophosphatemia, lipase increase, diarrhea, aspartate aminotransferase increase, and gait disturbance. Incidence of Grade 3 or 4 adverse events often associated with antiangiogenic therapy were: hypertension (2%), bleeding events (9%), thromboembolic event (4%), pulmonary embolism (7%), craniotomy wound dehiscence (4%), and perirectal abscess (2%). Of the 46 patients treated at the 175 mg dose level, 13 have had at least one serious adverse event (SAE) related to XL184. In addition, 89% of patients at this dose level had a dose interruption of XL184. Dose interruptions (14/18) and reductions (6/18) were observed in patients at the 125 mg dose level. The most frequent investigator reported non-serious adverse events resulting in dose reduction or interruption included: fatigue, palmar-plantar erythrodysesthesia, transaminase elevation, lipase and amylase elevation, and mucositis.

“The updated data from patients treated with the 175 mg dose of XL184 is consistent with what we have reported previously and continue to demonstrate that the compound is clinically active,” said Michael M. Morrissey, Ph.D. president of research and development at Exelixis. “While the data from the 125 mg dose cohort are still early, they are encouraging and we will continue to evaluate the suitability of this dose and potentially others for future clinical studies. We recently amended the protocol for this trial to allow physicians to intervene earlier in the adverse event process. We believe that more proactive management of adverse events may allow patients to reduce rather than interrupt their XL184 dosing. This trial in its totality is providing important information that will enable future decision making with respect to designing and implementing trials of XL184 in this patient population.”


 Bristol-Myers Squibb


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