Exelixis Releases Updated Phase 2 Data - Drug Discovery and Development

Exelixis, Inc. reported updated interim data from a fully enrolled cohort of patients with metastatic castration-resistant prostate cancer (CRPC) treated with cabozantinib (XL184) in a phase 2 adaptive randomized discontinuation trial (RDT).

The data provide additional patient experience and longer-term follow-up showing that cabozantinib results in resolution or stabilization of metastatic bone lesions on bone scan in the majority of patients evaluable by this method.

Cabozantinib treatment relieved or eliminated bone pain in the majority of patients, thus allowing for most who require narcotic analgesic medication to either reduce or eliminate the use of these medicines. Patients with partial or complete resolution of metastatic bone lesions by bone scan were more likely to remain free of disease progression after six months, experience pain relief, reduce or eliminate their use of narcotic analgesics, achieve tumor regression, and experience marked declines in markers of bone turnover when compared to those who did not achieve bone scan resolution.

Updated progression-free survival (PFS) data show that cabozantinib results in median PFS that appears to be similar in docetaxel-naïve and pretreated patients, and compares favorably to population matched historical controls. In the randomized discontinuation phase of the study, significant improvement in median PFS was observed in patients randomized to cabozantinib. Despite only 31 patients randomized at week 12, the results were highly statistically significant, suggestive of a sizable treatment effect over placebo. Durable increases in hemoglobin levels in anemic patients were also observed.

All 171 patients enrolled in the trial had measurable soft tissue disease per mRECIST, of which 37% had evidence of disease in liver or lung. The bone scan evaluable population includes 108 patients with evidence of bone metastasis, a baseline bone scan, and at least 1 post-baseline bone scan assessment. Prior therapies included docetaxel, abiraterone/MDV3100, and other cytotoxic and/or experimental agents.

In the randomized discontinuation phase, a total of 31 patients with stable disease (SD) at week 12 were randomized to either placebo or cabozantinib. From week 12 onward, the investigator-assessed median PFS is 6 weeks for the placebo group, and 21 weeks (for the cabozantinib group. The hazard ratio strongly favored the cabozantinib arm and corresponds to an 87% reduction in the risk of progression for patients treated with cabozantinib compared with placebo.