Trovagene presents final results from Phase 1b onvansertib study at ASH
Trovagene announced the presentation of final results from the company's Phase 1b study of onvansertib in patients with relapsed/refractory acute myeloid leukemia, or AML, in an oral session at the American Society of Hematology, or ASH, annual conference. The presentation highlighted the efficacy, durability of response, favorable safety and tolerability profile, as well as correlative biomarker data from the recently completed Phase 1b trial. Onvansertib is an oral, highly-selective Polo-like Kinase 1, or PLK1, inhibitor with a half-life of about 24 hours. PLK1 inhibition by onvansertib, assessed via a simple blood test and shown as changes in the phosphorylation of its direct substrate, the translational controlled tumor protein, TCTP, is a biomarker for identifying patients most likely to respond to treatment. Patients eligible for enrollment in the Phase 1b trial were treatment naive and not candidates for induction therapy or had relapsed/refractory disease to up to 3 prior regimens. Treatment was well tolerated through the first 5 dose escalation cohorts. Nine of the 71 SAEs were considered as possibly related to onvansertib and occurred at the higher dose levels: 40 mg/m2, 60 mg/m2 and 90 mg/m2. The maximum tolerated dose or recommended Phase 2 dose was established at 60 mg/m2. Six patients had a complete response; 9 had an ORR across LDAC and decitabine arms and doses. At the four higher dose levels, CR/CRi was observed in five of the 16 patients in the decitabine Arm and one of the nine patients in the LDAC Arm. Median time to achieve CR/CRi was 4 cycles. Median duration of response was five months. Four of six patients remain on treatment and in remission; duration of CR/CRi is respectively 1.5, 7, 8 and 11.5 months. Of the 24 evaluable patients, eight were biomarker positive across both arms. Among patients with at least 1 BM biopsy, biomarker positivity was associated with higher response to treatment: 67% of biomarker positive patients had a 20% decrease in blasts versus 18% in biomarker negative patients.CR/CRi was achieved in two biomarker positive patients but in none of the biomarker negative patients.