Abstract 4835
Background
Fluzoparib (FLU; SHR3162) is a selective PARP1 inhibitor that showed antitumour activity in xenograft models. We conducted a two-arm phase I, first-in-human, dose-escalation and expansion (D-Esc and D-Ex) trial of FLU in patients (pts) with advanced cancer. (ClinicalTrials.gov NCT03509636).
Methods
This was a 3 + 3 phase I D-Esc trial with a 3-level dose expansion (D-Ex) at 5 centers in China. Eligible pts were diagnosed with advanced solid tumors refractory to standard therapies or with no standard therapy. FLU was administered orally (daily or 2x/day (BID)) at 11 dose levels from 10–400 mg/day. The D-Ex arm evaluated FLU at 80, 100 or 150 mg BID in pts with ovarian cancer (OC). Endpoints included dose-finding, safety, tolerability, pharmacokinetics, and estimation of preliminary antitumor activity.
Results
79 pts with advanced solid tumors: (OC) [47; 59.5%]; breast cancer (BC) [16; 20.3%]; colorectal cancer [8; 10.1%], other tumors: [8; 10·1%]) were enrolled from 3/2015 to 3/2019. 48 pts were treated in the D-Esc arm and 31 in the D-Ex arm. The maximum tolerated dose (MTD) was 150 mg BID, with a half-life of 9 hours. Hematologic adverse events (AEs; all grades) included anemia (53.2%), thrombocytopenia (17.7%) and neutropenia (24.1%); main non-hematologic AEs (all grades) were fatigue (48.1%), vomiting (17.7%), nausea (34.2%) and decreased appetite (29.1%). Grade 3/4 AEs included anemia (7.6%) and neutropenia (5.1%). Objective responses were observed in 3 of 10 (30%) patients with platinum-sensitive OC and 1 of 13 (7·7%) with BC. Among patients treated with FLU ≥120 mg/day, median progression free survival (mPFS, range) was 4.4 mo (1–24) in OC; 10.2 mo (2–24) in platinum-sensitive OC; 3.5 mo (2–28) in BC. 11/43 OC and 2/16 BC had BRCAMut. In patients with BRCAMut, mPFS was 14 mo (one pt with BC at 160 mg/d) and 8.5 mo (range 1-24; 95%CI 0-17.1; 11 pts with OC). As of 3/1/2019, one pt with BC (BRCA wild type, 60 mg BID,28+mo) and 3 pts with BRCAMut OC (one at 80 mg BID, +21 mo; two at 150 mg BID, +15 and +14mo) continue on FLU.
Conclusions
The MTD of FLU was 150mg BID in advanced solid malignancies. FLU demonstrated single-agent antitumour activity in BC and OC, particularly in platinum-sensitive and BRCAMut OC.
Clinical trial identification
NCT03509636.
Editorial acknowledgement
Legal entity responsible for the study
Huiping Li.
Funding
Jiangsu Hengrui Medicine Co.
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
3425 - Feasibility and impact of prospective DPYD screening in the Irish population
Presenter: Mohammed Zameer
Session: Poster Display session 2
Resources:
Abstract
1972 - Diet-derived metabolites and the risk of colorectal cancer: a nested case-control study in a population-based cohort, the Singapore Chinese Health Study
Presenter: Dawn Chong
Session: Poster Display session 2
Resources:
Abstract
4103 - Loss of subcutaneous adipose tissue during chemotherapy predicts reduced survival in patients with incurable colorectal cancer undergoing palliative therapy
Presenter: Erin Stella Sullivan
Session: Poster Display session 2
Resources:
Abstract
4309 - Obese and overweight is associated with better prognosis in metastatic colorectal cancer patients treated with bevacizumab.
Presenter: Bozena Cybulska-Stopa
Session: Poster Display session 2
Resources:
Abstract
3554 - Patient characteristics associated with poor performance status, ECOG 2-3, and effect on survival in 1086 Finnish metastatic colorectal cancers (mCRC) nationwide (prospective RAXO study)
Presenter: Pia Österlund
Session: Poster Display session 2
Resources:
Abstract
4572 - Discovery and Diagnosis of Metastatic Colorectal Cancer (mCRC) in the Real World: Final Results from a European Survey
Presenter: Iga Rawicka
Session: Poster Display session 2
Resources:
Abstract
4783 - Adherence to recommended intake of calcium and colorectal cancer risk in the HEXA study
Presenter: Jeeyoo Lee
Session: Poster Display session 2
Resources:
Abstract
5106 - Body size, sex and sidedness of incident colorectal cancer in a prospective Swedish cohort study
Presenter: Christina Siesing
Session: Poster Display session 2
Resources:
Abstract
3364 - Middle East & North Africa Registry to characterize RAS mutation status and tumor specifications in recently diagnosed patients with metastatic colorectal cancer (MORE-RAS Study)
Presenter: Mohamed Oukkal
Session: Poster Display session 2
Resources:
Abstract
3668 - Patient Demographics and Management Landscape of Metastatic Colorectal Cancer in the Third Line Setting: real-world data in an Australian Population
Presenter: Sandy Tun Min
Session: Poster Display session 2
Resources:
Abstract