Conclusions: Trabectedin administered at 1.2 mg/m2 every 3 weeks resulted in confirmed 50% PSA decline in 18% in men with CRPC who had received prior taxane chemotherapy (Cohort B), a rate comparable to the 14% shown by taxane-resistant men from Cohort A. Most common adverse effects were myelosuppression, transaminitis, nausea and fatigue. Ongoing translational studies are designed to identify pts most likely to benefit from trabectedin treatment.