Exelixis, Inc. (NASDAQ:EXEL) today reported interim data from the cohort of patients with metastatic castration-resistant prostate cancer (CRPC) treated with XL184 in an ongoing phase 2 adaptive randomized discontinuation trial (RDT). David C. Smith, M.D., Professor, Departments of Internal Medicine and Urology at the University of Michigan, will present the data in the Molecular-Targeted Therapies-Clinical Trials poster session (Abstract #406) on Thursday, November 18th, at the 22nd EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics in Berlin, Germany.
“These data suggest that XL184 has a novel and differentiated clinical profile in CRPC, and will provide critical guidance in defining our high priority development activities for XL184 in 2011.”
XL184 Activity Against Bone and Soft Tissue Lesions in CRPC
As of the November 1, 2010 cut-off date, a total of 99 patients were enrolled in the CRPC cohort, with 34 currently evaluable for tumor response per RECIST criteria and 20 with evidence of bone metastasis evaluable for changes in bone scan. The trial includes patients with (57%) and without (43%) prior docetaxel therapy.
Impact on Metastatic Bone Lesions
Nineteen of 20 patients (95%) achieved either complete or partial resolution of lesions on bone scan by independent review, with most resolving at the first post-baseline assessment at 6 weeks. Bone scans use a radiotracer imaging agent that binds to sites of new bone formation, which reflect sites of metastatic disease in bone. Multiple cases of complete or near complete resolution were observed in both docetaxel-pretreated and docetaxel-naïve subgroups. To date, a single docetaxel-pretreated patient achieved stabilization of bone scan as his best evaluation, and no patient exhibited worsening on bone scan as his best time point assessment.
Bone scan resolution was associated with investigator reported improvements in bone pain, with the majority of symptomatic patients experiencing pain relief. In addition, most patients exhibited decreases in the blood-based bone metabolism biomarkers alkaline phosphatase (ALP) and C-terminal telopeptides of type 1 collagen (CTx), which are often increased in patients with metastatic bone lesions who are at risk for skeletal morbidity. Patients with anemia at baseline exhibited maximal increases in hemoglobin levels ranging from 1.2 to 3.4 g/dL from baseline.
Impact on Soft Tissue Lesions
The week-12 disease control rate (DCR) was 71%. Tumor shrinkage was observed in 38 of 55 patients (69%) with measurable soft-tissue metastatic lesions and at least one post-baseline scan. To date, 3 of 34 patients (9%) evaluable by RECIST achieved a confirmed partial response (PR). Of note, response criteria in common use today (including RECIST) do not incorporate bone scan findings. Stable disease (SD) was reported in 25 patients (74%) including 2 unconfirmed PRs. Changes in PSA are reasonably well correlated with response to hormonally acting agents and cytotoxic chemotherapy. In contrast, XL184 treated patients experiencing tumor regression and improvement in bone pain demonstrated variable impact on PSA levels. Thus, the commonly used PSA marker does not appear to be a reliable indicator for the activity of XL184 in this disease.
Safety and Tolerability
Safety data are available for 49 patients who had at least 6 weeks of follow-up. The most common Grade ≥ 3 AEs, regardless of causality were fatigue (14%), hypertension, PPE syndrome (each 6%), hemorrhage, nausea (each 4%), diarrhea, cough, and rash (each 2%).
"CRPC is a leading cause of cancer-related death in men in the United States and Europe," said Dr. Smith. "Recent advances in systemic therapy have had at best a modest impact on survival, and virtually all patients will succumb to this disease. Bone metastases result in significant morbidity for patients with CRPC, including fractures and pain, which can substantially reduce quality of life and increase mortality. The results of this study to date suggest that XL184 has activity against both soft tissue and bone metastatic lesions. Based on this activity, further evaluation of XL184 in CRPC is clearly indicated, as the data suggest that the compound may provide clinical benefit to a population of patients with few treatment options that effectively target both components of this disease."
"The initial activity of XL184 against metastatic soft-tissue and bone lesions in CRPC patients is very encouraging," said Michael M. Morrissey, Ph.D., president and chief executive officer of Exelixis. "These data suggest that XL184 has a novel and differentiated clinical profile in CRPC, and will provide critical guidance in defining our high priority development activities for XL184 in 2011."
To access the clinical data poster mentioned in this press release, please visit www.exelixis.com.
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