Onconova presents rigosertib with azacitidine data at ASH

Onconova Therapeutics announced the presentation of the efficacy and safety results of oral rigosertib in combination with azacitidine in patients with HR-MDS reported at an oral presentation during the American Society of Hematology, or ASH. Rigosertib, the company’s lead compound, is being evaluated in both intravenous and oral forms. Seventy-four patients were treated with a median age of 69 years at nine clinical sites and received either 840 mg or 1,120 mg of oral rigosertib daily divided into two doses, in combination with a standard dose of injectable azacitidine. Of the 55 evaluable patients, 29 patients were treated with a daily dose of 1,120 mg of oral rigosertib, either 560 mg twice daily or 840 mg in the a.m. and 280 mg in the afternoon. Twenty-six patients were treated with 560 mg in the AM and 280 mg in the PM for the first three weeks of a four-week cycle. All patients also received 75 mg/m2/day SC or IV azacitidine during the second week of the four-week cycle. The median duration of treatment for the HMA naive and HMA failed patients was 7.8 and 4.9 months respectively. The median duration of response in these groups was 12.2 and 10.8 months, respectively. The overall response rate, or ORR, using the IWG 2006 criteria, in 29 HMA naive patients was 90%, including 10 patients with complete remission, or CR. Among the 26 evaluable HMA-failed patients the ORR was 54% including 8% CR or PR. The median time to initial and best response were 1 and 4 cycles in the HMA naive group and 2 and 5 cycles in the HMA failed group. The safety population received at least 1 dose of oral rigosertib. The combination was well tolerated. Other than genitourinary adverse events, or AEs, the AE profile was similar to those described for azacitidine alone in this patient population. Genitourinary AEs, including hematuria and dysuria were observed. A safety optimization strategy was implemented for the higher dose cohort of 1,120 mg of oral rigosertib. These strategies included earlier in the day administration of the PM dose, oral hydration, monitoring of urinary pH and mandatory bladder emptying at night. Collectively these strategies resulted in mitigation of the target genitourinary AEs, including reduction of genitourinary grade 3 AEs reported from an earlier cohort despite receiving a higher dose of oral rigosertib. In conclusion, oral rigosertib in combination with azacitidine was well tolerated in HMA naive and HMA failed HR-MDS patients. The combination produced an encouraging rate of overall response and complete remission in both groups. The safety optimization strategies and increased dose exploration of oral rigosertib in the combination is leading to the development of a pivotal Phase 3 trial in HMA and chemotherapy naive patients. Onconova plans to meet with the FDA to discuss the results of the Phase 2 trial and the planned Phase 3 trial, and to seek a special protocol assessment. The company has partnered rigosertib with SymBio Pharmaceuticals, for Japan and Korea, and with Pint Pharma for Latin American countries. Both partners have indicated their interest in participating in the proposed new pivotal Phase 3 trial by enrolling patients in their respective territories. SymBio is currently conducting Phase 1 studies with oral rigosertib in Japan and also participating in the Phase 3 global INSPIRE trial. The company is also actively seeking additional collaborations for rigosertib in other geographies.

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