Abstract CT050: A phase I dose escalation study of BGB-290 in Chinese subjects with advanced ovarian, fallopian, and primary peritoneal, or advanced triple-negative breast cancer

Background BGB-290 is a selective inhibitor of poly (ADP-ribose) polymerases (PARP) 1 and 2 that crosses the blood-brain barrier, showed potent DNA-PARP trapping, and demonstrated robust antitumor activity in nonclinical models. In a first-in-human study (NCT02361723), BGB-290 was generally well tolerated and showed promising preliminary antitumor activity, notably in patients (pts) with high-grade non-mucinous ovarian cancer (HGOC). The recommended Phase 2 dose (RP2D) was established as 60 mg PO BID. Methods This ongoing dose-escalation (DE)/expansion study (NCT03333915) is enrolling Chinese pts with advanced HGOC, including fallopian and primary peritoneal cancer, or triple-negative breast cancer (TNBC). DE cohorts were designed to confirm the previously established RP2D. Patients with germline BRCA1/2 mutation (BRCA+) were retrospectively identified by central testing. The primary endpoint was safety and tolerability of BGB-290 in Chinese patients as per CTCAE v4.03. Key secondary endpoints were pharmacokinetics (PK) and antitumor activity as per RECIST v1.1. Results As of 25 Sep 2017, 15 pts (HGOC: n=9; TNBC: n=6) were enrolled in DE. Median age was 49 years (range: 32–70), ECOG score was 0 (n=2) or 1 (n=13), and 7 of 15 pts were germline BRCA+ (HGOC: n=5; TNBC: n=2). BGB-290 BID dose levels of 20 mg (n=4), 40 mg (n=4), and 60 mg (n=7) were evaluated. Most common treatment-related adverse events (AEs) were asthenia (n=12), nausea (n=12), decreased appetite (n=9), decreased white blood cell (WBC) count (n=9), anemia (n= 8), and decreased neutrophil count (n=7). Grade 3 AEs occurring in ≥2 pts were anemia (n=5), decreased neutrophil count, and decreased WBC (n=2 each). No ≥ Grade 4 AEs were reported. Serious AEs (abdominal infection, ileus, and pleural effusion, n=1 each) were determined not related to BGB-290. No dose-limiting toxicities were reported, and the RP2D was confirmed as 60 mg PO BID. After a single dose, BGB-290 was rapidly absorbed (median Tmax=1 hr) with a t1/2 of ~12 hr and showed near dose-proportional increases for both Cmax and AUC0-inf. Preliminary activity showed 2 confirmed PRs (BRCA+=1) and 6 SD (BRCA+=4) in HGOC pts (all platinum-resistant/refractory); median duration of treatment is 133 days (range: 8–260) with 5 pts still on treatment. Best response in the 5 TNBC pts was PD (BRCA+=1). Conclusions BGB-290 at 20, 40, and 60 mg PO BID was generally well tolerated in Chinese pts with advanced HGOC or TNBC. The previously established