Dataset Information

Phase I dose-escalation and expansion study of PARP inhibitor, fluzoparib (SHR3162), in patients with advanced solid tumors.

ABSTRACT:

Objective

Fluzoparib (SHR3162) is a novel, potent poly(ADP-ribose) polymerases (PARP)1, 2 inhibitor that showed anti-tumor activity in xenograft models. We conducted a phase I, first-in-human, dose-escalation and expansion (D-Esc and D-Ex) trial in patients with advanced solid cancer.

Methods

This was a 3+3 phase I D-Esc trial with a 3-level D-Ex at 5 hospitals in China. Eligible patients for D-Esc had advanced solid tumors refractory to standard therapies, and D-Ex enrolled patients with ovarian cancer (OC). Fluzoparib was administered orally once or twice daily (bid) at 11 dose levels from 10 to 400 mg/d. Endpoints included dose-finding, safety, pharmacokinetics, and antitumor activity.

Results

Seventy-nine patients were enrolled from March, 2015 to January, 2018 [OC (47, 59.5%); breast cancer (BC) (16, 20.3%); colorectal cancer (8, 10.1%), other tumors (8, 10.1%)]; 48 patients 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 9.14 h. Grade 3/4 adverse events included anemia (7.6%) and neutropenia (5.1%). The objective response rate (ORR) was 30% (3/10) in patients with platinum-sensitive OC and 7.7% (1/13) in patients with BC. Among patients treated with fluzoparib ≥120 mg/d, median progression-free survival (mPFS) was 7.2 [95% confidence interval (95% CI), 1.8-9.3] months in OC, 9.3 (95% CI, 7.2-9.3) months in platinum-sensitive OC, and 3.5 (range, 2.0-28.0) months in BC. In patients with germline BC susceptibility gene mutation (gBRCA ^Mut) (11/43 OC; 2/16 BC), mPFS was 8.9 months for OC (range, 1.0-23.2; 95% CI, 1.0-16.8) and 14 and 28 months for BC (those two patients both also had somaticBRCA ^Mut).

Conclusions

The MTD of fluzoparib was 150 mg bid in advanced solid malignancies. Fluzoparib demonstrated single-agent antitumor activity in BC and OC, particularly in BRCA ^Mut and platinum-sensitive OC.

SUBMITTER: Li H

PROVIDER: S-EPMC7369176 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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Publications

Phase I dose-escalation and expansion study of PARP inhibitor, fluzoparib (SHR3162), in patients with advanced solid tumors.

Li Huiping H Liu Rongrui R Shao Bin B Ran Ran R Song Guohong G Wang Ke K Shi Yehui Y Liu Jihong J Hu Wenjing W Chen Fu F Liu Xiaoran X Zhang Gairong G Zhao Chuanhua C Jia Ru R Wang Quanren Q Rugo Hope S HS Zhang Yifan Y Li Guangze G Xu Jianming J

Chinese journal of cancer research = Chung-kuo yen cheng yen chiu 20200601 3

<h4>Objective</h4>Fluzoparib (SHR3162) is a novel, potent poly(ADP-ribose) polymerases (PARP)1, 2 inhibitor that showed anti-tumor activity in xenograft models. We conducted a phase I, first-in-human, dose-escalation and expansion (D-Esc and D-Ex) trial in patients with advanced solid cancer.<h4>Methods</h4>This was a 3+3 phase I D-Esc trial with a 3-level D-Ex at 5 hospitals in China. Eligible patients for D-Esc had advanced solid tumors refractory to standard therapies, and D-Ex enrolled patie ...[more]

PMID: 32694901

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Dataset Information

Phase I dose-escalation and expansion study of PARP inhibitor, fluzoparib (SHR3162), in patients with advanced solid tumors.

Objective

Methods

Results

Conclusions

Publications

Phase I dose-escalation and expansion study of PARP inhibitor, fluzoparib (SHR3162), in patients with advanced solid tumors.

Similar Datasets

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