Open AccessPamiparib dose escalation in Chinese patients with non‐mucinous high‐grade ovarian cancer or advanced triple‐negative breast cancer
Author(s) -
Xu Binghe,
Yin Yongmei,
Dong Mei,
Song Yan,
Li Wei,
Huang Xiang,
Wang Tongshan,
He Jing,
Mu Xiyan,
Li Li,
Mu Song,
Zhang Wa,
Li Miao
Publication year - 2021
Publication title -
cancer medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 53
ISSN - 2045-7634
DOI - 10.1002/cam4.3575
Subject(s) - medicine , tolerability , triple negative breast cancer , adverse effect , progressive disease , breast cancer , nausea , gastroenterology , clinical endpoint , ovarian cancer , oncology , phases of clinical research , cancer , chemotherapy , clinical trial
Background The recommended phase 2 dose (RP2D) of pamiparib, an investigational PARP1/2 inhibitor, was established as 60 mg twice daily (BID) in a first‐in‐human (FIH) study (NCT02361723). Methods Chinese patients with advanced non‐mucinous high‐grade ovarian cancer (HGOC) or triple‐negative breast cancer (TNBC) whose disease either progressed despite standard therapy, or for which there is no standard therapy were enrolled in the dose‐escalation (DE) portion of a phase 1/2 study (NCT03333915). The primary endpoint was safety/tolerability; secondary objectives were pharmacokinetics and antitumor activity. BRCA1 / 2 mutation status was retrospectively evaluated. Results Nine HGOC and six TNBC patients (N = 15; n = 4, 20 mg; n = 4, 40 mg; n = 7, 60 mg) were enrolled; as of 30 September 2019, one HGOC patient remained on treatment. Seven patients (n = 5, HGOC; n = 2, TNBC) had germline BRCA1 / 2 mutation ( gBRCA mut ); all HGOC patients were resistant/refractory to platinum. Asthenia and nausea (n = 12 each) were the most common treatment‐related adverse events (TRAEs). Decreased hemoglobin was the most common grade 3 TRAE (n = 3); no grade ≥4 AEs were observed. No dose‐limiting toxicities (DLTs) were reported. Pamiparib plasma exposure was similar to exposure observed in the FIH study after a single‐dose administration, albeit slightly higher at steady state. Among 13 RECIST‐evaluable patients, two with HGOC ( gBRCA mut , n = 1) achieved a confirmed partial response and six with HGOC ( gBRCA mut , n = 4) achieved stable disease; all TNBC RECIST‐evaluable patients (n = 5) reported progressive disease. Conclusions Pamiparib was generally well tolerated in Chinese patients, with durable responses observed in patients with HGOC. Based on these results, pamiparib 60 mg BID was confirmed as the RP2D.