Pamiparib, an investigational, selective inhibitor of PARP1/2, has PARP-DNA complex trapping capabilities. The first-in-human study (NCT02361723) established the pamiparib phase II dose as 60 mg po BID. Responses were reported in BRCA mutated or wild-type and platinum-sensitive/resistant aOC. Here we present phase II results from an ongoing phase I/II study in Chinese pts with advanced solid tumors (NCT03333915).
Patients with platinum-sensitive (cohort 1) and platinum-resistant (cohort 2) aOC were enrolled. Patients with known/suspected deleterious germline BRCA1/2 mutation and ≥2 prior lines of chemotherapy were eligible. The primary endpoint was objective response rate (ORR) assessed by an independent review committee (ORRIRC) per RECIST v1.1.
As of 2 Feb 2020, 113 pts (cohort 1, n=90; cohort 2, n=23) were enrolled. Median age was 54 yr (range: 34-79), 25.6% (n=29) of pts had received ≥4 prior systemic chemotherapy lines, and 54.0% (n=61) of pts had an ECOG score of 1 at study entry. At data cutoff, median follow-up was 12.2 mo (range: 0.2-21.5). Across both cohorts, pamiparib showed preliminary antitumor activity (Table). In cohort 1, confirmed ORRIRC was 64.6%, median DoR was 14.5 mo (95% CI, 11.1-NE), progression-free survival (PFS) was 15.2 mo (95% CI, 10.35-NE), and median overall survival (OS) was not yet mature. In cohort 2, confirmed ORRIRC was 31.6%, median DoR was 11.1 mo (95% CI, 4.21-NE), median PFS was 6.2 mo (95% CI, 4.11-NE), and median OS was 13.6 mo (95% CI, 7.13-NE). Overall, the most common treatment-related AE was anemia (any grade, 89%; grade ≥3, 42%); following a per-protocol proposed dose modification algorithm, the incidence of grade ≥3 anemia was reduced to 25.6%. Table: 820P
|Efficacy-evaluable population||Cohort 1 (n=82)||Cohort 2 (n=19)|
|Best overall response, n (%)|
|Complete response||8 (9.8)||0 (0)|
|Partial response||45 (54.9)||6 (31.6)|
|Stable disease||25 (30.5)||12 (63.2)|
|Progressive disease||4 (4.9)||1 (5.3)|
|Objective response rate, % (95% CI)|
|Confirmed||64.6 (53.3-74.9)||31.6 (12.6-56.6)|
|Disease control rate, % (95% CI)||95.1 (88.0-98.7)||94.7 (74.0-99.9)|
|Clinical benefit rate, % (95% CI)||74.4 (63.6-83.4)||52.6 (28.9-75.6)|
|Time to response, median mo (range)||1.68 (1.3-6.3)||1.38 (1.2-1.4)|
|Duration of response, median mo (95% CI)||14.5 (11.1-NE)||11.1 (4.21-NE)|
|PFS, median mo (95% CI)||15.2 (10.35-NE)||6.2 (4.11-NE)|
Abbreviations: NE, not estimable; PFS, progression-free survival.
Promising antitumor activity was observed in pts with platinum-sensitive/resistant aOC. Pamiparib was generally tolerated, with no new safety signals. Pamiparib is being evaluated as monotherapy and combination therapy for other solid tumors.
Clinical trial identification
Writing and editorial assistance was provided by Regina Switzer, PhD, Cathy R. Winter, PhD, and Elizabeth Hermans, PhD (OPEN Health Medical Communications, Chicago. IL), and funded by the study sponsor.
Legal entity responsible for the study
X. Wu, J. Wang, B. Kong, R. Yin, W. Sun, Q. Zhou, S. Zhang, D. Wang, H. Shi, Y. Gao, Y. Huang, G. Li, X. Wang: Research grant/Funding (institution): BeiGene, Ltd. L. Li, X. Mu, M. Li: Shareholder/Stockholder/Stock options, Full/Part-time employment: BeiGene, Ltd. All other authors have declared no conflicts of interest.