7115 Background: Brain metastases (BM) represent a common cause of morbidity and mortality among cancer patients. WBRT is the primary treatment for these patients; however, differences in the prognosis of these patients have been reported for those with synchronous disease (simultaneous diagnosis of primary tumor and BM within 1 month) versus metachronous (time of diagnosis > 1 month apart). RSR13 (efaproxiral), a novel radiation sensitizer, reduces tissue hypoxia and therefore enhances the efficacy of radiation therapy. Methods: A randomized, open-label phase 3 study compared the survival of patients receiving RSR13 (75–100 mg/kg) + O2 with standard WBRT (3 Gy/d fractions over 10 days) versus patients receiving WBRT + O2 alone. The primary endpoint of the study was survival. Results: The subset of patients with BM originating from NSCLC (n=299) was the largest of the 538 patients enrolled in the study. Patients in the RSR13 arm with NSCLC and metachronous disease (n=75) had an MST of 5.39 months compared with an MST of 4.37 months in the Control arm (n=87) [HR=0.77, 95% CI (0.55, 1.09)]. The MST in patients with synchronous disease did not differ between the 2 treatment arms (RSR13 [n=73] 4.5 months; Control [n=64] 4.8 months). Conclusions: Patients with primary NSCLC and BM diagnosed more than 1 month after the primary diagnosis experienced a 27% reduction in the risk of death when treated with the novel radiation sensitizer RSR13 and WBRT plus supplemental oxygen compared with Control. These encouraging results warrant further investigation. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Allos Therapeutics, Inc. Allos Therapeutics, Inc. Allos Therapeutics, Inc. Allos Therapeutics, Inc.