574P Updated Results of Phase I Study of Senaparib (IMP4297) in Australian Patients with Advanced Solid Tumours

PARP inhibitors are promising anti-cancer agents with proven clinical activity based on mechanism of synthetic lethality. Senaparib (previously known as IMP4297) is a novel highly potent and selective oral PARP1/2 inhibitor with strong antitumor activity in preclinical studies. This first in human study investigated the tolerability, safety, PK, and preliminary antitumor activity of senaparib in Australia. Adults with advanced, refractory solid tumours received senaparib orally QD, starting at 2mg. Dose escalation used a traditional 3+3 design and a modified Fibonacci sequence with 3-6 patients per cohort. DLT was evaluated in the first cycle. Dose expansion cohort enrolled patients with BRCA mutated (BRCA+) advanced solid tumors. As of Feb 25, 2020, 39 patients were enrolled in 10 dose levels (2 to 150mg). No DLTs were observed. The most frequent treatment emergent adverse events (TEAE) were headache (25.6%), fatigue (25.6%), constipation (17.9%), diarrhea (15.4%), nausea (12.8%), vomiting (12.8%) and anemia (10.3%). Treatment-related adverse events (TRAE) were observed in 8 (21%) patients starting from 40mg dose group. The most frequent TRAEs were nausea (8%), thrombocytopenia (5%) and fatigue (5%). An event of grade 4 thrombopenia in 80mg was the only serious TRAE. Four (10%) patients interrupted and 6 (15%) patients discontinued therapy due to AEs. The overall ORR and DCR was 15% and 85% respectively. In 8 evaluable ovarian cancer patients, ORR was 38% and DCR was 75%. A prolonged (> 20 months) PR response was observed in one BRCA+ ovarian cancer patient and a > 50% decrease of PSA for 11 months was observed in one BRCA- prostate cancer patients. The plasma exposure increased proportionally with doses ranging from 2mg to 80mg and became nonlinear ranging from 80mg to150mg cohorts. Senaparib demonstrated encouraging clinical benefit and a favorable tolerability profile in patients with advanced solid tumour. The 100 mg orally QD was selected as the RP2D in Australia based on safety, pharmacokinetics and clinical activity. Clinical trial information: NCT03507543.