Abstract 577P
Background
Seneparib (previously known as IMP4297) is a novel oral PARP inhibitor which is 20-fold more potent than olaparib in vivo and showing strong antitumor activity in preclinical studies. This phase I study of senaparib is to evaluate PK, safety/tolerability and preliminary antitumor activity in patients with advanced solid tumours.
Methods
The primary objective was to evaluate the safety profile of senaparib given orally QD, including the identification of the maximum tolerated dose and the recommended phase II dose (RP2D). Dose escalation was guided by a modified Fibonacci sequence, starting at 2 mg/day, with a traditional 3+3 design. Dose expansion cohort was planned to start from the dose level in which efficacy was observed.
Results
As of Feb 29, 2020, 54 patients, including 34 BRCA mutation carriers, had been enrolled at 2-120 mg dose level. No DLT was observed. The most frequent treatment-related adverse events (TRAE) were anemia (48%), followed by leukopenia (41%), thrombocytopenia (26%), neutropenia (22%), nausea (22%) and fatigue (22%). Most of them were grade 1 or 2 in severity. Seven (13%) patients interrupted and 3 (6%) patients discontinued treatment due to AEs. Among 41 pts with at least one follow-up RECIST 1.1 assessment, 6 germline BRCA+ patients, 1 somatic BRCA+ patient and 2 BRCA- patients had PR, including one long-lasting PR over 9 months (BRCA+ ovarian cancer, 60mg). The overall ORR and DCR was 22% and 61% respectively. In 17 BRCA+ ovarian cancer patients, the ORR is 24% and DCR is 82%. An alternative dosing regimen of 50mg bid is ongoing to compare PK characteristic between QD and BID dosing.
Conclusions
We further confirmed senaparib is well-tolerated, with mild to moderate haematologic toxicity as the most frequent TRAEs and showed encouraging signs of clinical activity. The 100 mg orally QD was selected as the RP2D based on safety, pharmacokinetics and clinical activity.
Clinical trial identification
NCT03508011.
Editorial acknowledgement
Legal entity responsible for the study
IMPACT Therapeutics Inc.
Funding
IMPACT Therapeutics Inc.
Disclosure
All authors have declared no conflicts of interest.