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
5063 - Does Nutritional Status Affect Treatment Tolarability, Response and Survival in Metastatic Gastric Cancer Patients? Results of Prospective Multicenter Study
Presenter: Senem Karabulut
Session: Poster Display session 2
Resources:
Abstract
2717 - Ramucirumab use in patients with Advanced Gastric Cancer (AGC) or gastro-oesophageal junction (GEJ) adenocarcinoma in Spain: RAMIS observational study
Presenter: Federico Longo Munoz
Session: Poster Display session 2
Resources:
Abstract
3187 - Gastrectomy plus chemotherapy versus chemotherapy alone for advanced gastric cancer with a single non-curable factor: Exploratory analysis in the patients who were enrolled in JCOG0705/KGCA01 phase III trial (REGATTA) and could continue chemotherapy
Presenter: Takaki Yoshikawa
Session: Poster Display session 2
Resources:
Abstract
4765 - A prospective observational study on the optimal maintenance strategy in HER2-positive advanced gastric cancer treated with trastuzumab based therapy
Presenter: Qian Li
Session: Poster Display session 2
Resources:
Abstract
3500 - Randomised phase 2 trial of first-line docetaxel, carboplatin, capecitabine (CTX) and epirubicin, oxaliplatin, capecitabine (EOX) in advanced esophagogastric adenocarcinoma (SEED)
Presenter: Peter Petersen
Session: Poster Display session 2
Resources:
Abstract
5197 - Ramucirumab in the treatment of refractory metastatic gastric cancer: results from the RamSelGa trial.
Presenter: Alexey Tryakin
Session: Poster Display session 2
Resources:
Abstract
2011 - Regorafenib in combination with Paclitaxel for beyond first-line treatment of advanced esophagogastric cancer (REPEAT): a phase Ib trial with expansion cohort
Presenter: Mohammed Khurshed
Session: Poster Display session 2
Resources:
Abstract
2117 - The relationship between the survival and fixed dosing of S-1 in advanced gastric cancer patients by pooled analysis using individual data from four Japanese randomized phase III trials
Presenter: Wataru Ichikawa
Session: Poster Display session 2
Resources:
Abstract
2669 - A Phase 1b Study of Oraxol in Combination with Ramucirumab in Patients with Gastric or Esophageal Cancers who failed previous chemotherapy
Presenter: Ming Huang Chen
Session: Poster Display session 2
Resources:
Abstract
3240 - Efficacy and safety of trifluridine/tipiracil (FTD/TPI) in European patients with heavily pretreated metastatic gastric cancer (mGC): an analysis of the TAGS study
Presenter: Maria Alsina
Session: Poster Display session 2
Resources:
Abstract