Ariel 3 Phase III study of rucaparib comprehensive dataset presented at ESMO.- Clovis Oncology.

Clovis Oncology, Inc. announced the first presentation of a comprehensive dataset from its Phase III ARIEL3 study of rucaparib at the 2017 European Society for Medical Oncology (ESMO) Congress taking place in Madrid. The ARIEL3 study successfully achieved its primary endpoint and key secondary endpoint, demonstrating improved progression-free survival (PFS) by both investigator review and blinded independent central review (BICR) in each of the three populations studied. The data will be presented by Professor Jonathan A. Ledermann, MD, European and ROW Principal Investigator for the ARIEL3 study.

1.Significant Improvement in PFS in the tBRCAmut Patient Population : The most robust clinical outcomes were observed among ARIEL3 patients with a germline or somatic BRCA mutation (n=196). By investigator review, the rucaparib arm successfully achieved statistical significance over the placebo arm for the primary endpoint of PFS with a hazard ratio of 0.23 (95% CI, 0.16-0.34; p<0.0001). The median PFS for the tBRCAmut patients treated with rucaparib was 16.6 months (95% CI, 13.4-22.9) vs. 5.4 months (95% CI, 3.4-6.7) among those who received placebo. . By BICR, the rucaparib arm improved PFS over the placebo arm with a hazard ratio of 0.20 (95% CI, 0.13-0.32; p<0.0001). The median PFS for the tBRCAmut patients treated with rucaparib was 26.8 months (95% CI, 19.2-NR) vs. 5.4 months (95% CI, 4.9-8.1) among those who received placebo.. Results were consistent for the germline BRCA (n=130) and somatic BRCA (n=56) populations. 2.Significant Improvement in PFS in the HRD Patient Population -This population included patients with a germline or somatic mutation of BRCA, as well as those whose tumors were BRCA wild type (BRCAwt) but determined to be HRD as defined by a Foundation Medicine assay (n=354). By investigator review, the rucaparib arm successfully achieved statistical significance over the placebo arm for the primary endpoint of PFS with a hazard ratio of 0.32 (95% CI, 0.24-0.42; p<0.0001). The median PFS for the HRD patients treated with rucaparib was 13.6 months (95% CI, 10.9-16.2) vs. 5.4 months (95% CI, 5.1-5.6) among those who received placebo. By BICR, the rucaparib arm improved PFS over the placebo arm with a hazard ratio of 0.34 (95% CI, 0.24-0.47; p<0.0001). The median PFS for the HRD patients treated with rucaparib was 22.9 months (95% CI, 16.2-NR) vs. 5.5 months (95% CI, 5.1-7.4) among those who received placebo. 3.Significant Improvement in PFS in All Patients Studied - Rucaparib also showed statistical significance in all 564 patients enrolled in the study. By investigator review, the rucaparib arm successfully achieved statistical significance over the placebo arm for the primary endpoint of PFS with a hazard ratio of 0.36 (95% CI, 0.30-0.45; p<0.0001). The median PFS for all patients treated with rucaparib was 10.8 months (95% CI, 8.3-11.4) vs. 5.4 months (95% CI, 5.3-5.5) for those who received placebo. By BICR, the rucaparib arm improved PFS over the placebo arm with a hazard ratio of 0.35 (95% CI, 0.28-0.45; p<0.0001). The median PFS for all patients enrolled in ARIEL3 and treated with rucaparib was 13.7 months (95% CI, 11.0-19.1) vs. 5.4 months (95% CI, 5.1-5.5) for those who received placebo. 4.Exploratory PFS Endpoint Achieved in BRCAwt/LOH High Subgroup - The exploratory PFS endpoint was achieved in the 158 patients identified as BRCAwt LOH high. By investigator review, the rucaparib arm successfully achieved its endpoint over the placebo arm for the primary endpoint of PFS with a hazard ratio of 0.44 (95% CI, 0.29-0.66; p<0.0001). The median PFS for these patients treated with rucaparib was 9.7 months (95% CI, 7.9-13.1) vs. 5.4 months (95% CI, 4.1-5.7) for those who received placebo. By BICR, the rucaparib arm improved PFS over the placebo arm with a hazard ratio of 0.55 (95% CI, 0.35-0.89; p=0.0135). The median PFS for these patients treated with rucaparib was 11.1 months (95% CI, 8.2-NR) vs. 5.6 months (95% CI, 2.9-8.2) for those who received placebo. 5. Exploratory PFS Endpoint Achieved in BRCAwt/LOH Low Subgroup - The exploratory PFS endpoint was achieved in the 161 patients identified as BRCAwt and LOH low. By investigator review, the rucaparib arm successfully achieved its endpoint over the placebo arm for the primary endpoint of PFS with a hazard ratio of 0.58 (95% CI, 0.40-0.85; p=0.0049). The median PFS for these patients treated with rucaparib was 6.7 months (95% CI, 5.4-9.1) vs. 5.4 months (95% CI, 5.3-7.4) for those who received placebo. By BICR, the rucaparib arm improved PFS over the placebo arm with a hazard ratio of 0.47 (95% CI, 0.31-0.71; p=0.0003). The median PFS for these patients treated with rucaparib was 8.2 months (95% CI, 5.6-10.1) vs. 5.3 months (95% CI, 2.8-5.5) for those who received placebo. 6. Exploratory Endpoint of Response Rate - Enrollment in ARIEL3 included one-third of patients who had achieved a complete response to their prior platinum-based therapy, and two-thirds of patients who had achieved a partial response to their prior platinum-based therapy. Of those with a partial response, 37% had measurable disease at the time of enrollment and were therefore evaluable for response. By investigator-assessed RECISTv1.1, the confirmed objective response rate (ORR) in the tBRCAmut group treated with rucaparib was 38% (15/40), of these, 18% (7/40) were complete responses. This compared with 9% (2/23) ORR in the placebo group (p=0.0055) and 0% complete responses. The confirmed ORR in the HRD group treated with rucaparib was 27% (23/85), of these, 12% (10/85) were complete responses. This compared with 7% (3/41) ORR in the placebo group (p=0.05) and 0% complete responses. Finally, among the intent-to-treat population, the confirmed ORR in patients treated with rucaparib was 18% (26/141), of these 7% (10/141) were complete responses. This compared with 8% (5/66) ORR in the placebo group (p=0.05) and 2% (1/66) complete response.