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Ref Type Journal Article
PMID (32694901)
Authors Li H, Liu R, Shao B, Ran R, Song G, Wang K, Shi Y, Liu J, Hu W, Chen F, Liu X, Zhang G, Zhao C, Jia R, Wang Q, Rugo HS, Zhang Y, Li G, Xu J
Title Phase I dose-escalation and expansion study of PARP inhibitor, fluzoparib (SHR3162), in patients with advanced solid tumors.
Journal Chinese journal of cancer research = Chung-kuo yen cheng yen chiu
Vol 32
Issue 3
Date 2020 Jun
URL
Abstract Text 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.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.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 (gBRCAMut) (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 somaticBRCAMut).The MTD of fluzoparib was 150 mg bid in advanced solid malignancies. Fluzoparib demonstrated single-agent antitumor activity in BC and OC, particularly in BRCAMut and platinum-sensitive OC.

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Molecular Profile Treatment Approach
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Drugs Efficacy Evidence Clinical Trials
Drug Name Trade Name Synonyms Drug Classes Drug Description
Fluzoparib HS10160|SHR-3162|SHR3162 PARP Inhibitor (Pan) 22 Fluzoparib (SHR3162) is a PARP inhibitor, which potentially induces DNA damage, cell cycle arrest and apoptosis, and inhibits cell proliferation and tumor growth (PMID: 30663191, PMID: 32694901).
Gene Variant Impact Protein Effect Variant Description Associated with drug Resistance
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
Unknown unknown breast cancer not applicable Fluzoparib Phase I Actionable In a Phase I trial, Fluzoparib treatment was well tolerated, and among evaluable breast cancer patients resulted in an overall response rate (ORR) of 7.7% (1/13) and stable disease at 24 weeks in 5/13, for a disease control rate of 23.1%, and a median progression-free survival (mPFS) of 3.5 months in patients dosed at >120mg/d, with 1 patient still on treatment at 28 months (PMID: 32694901; NCT03509636). 32694901
Unknown unknown ovarian cancer not applicable Fluzoparib Phase I Actionable In a Phase I trial, Fluzoparib treatment was well tolerated, and among evaluable ovarian cancer patients resulted in an overall response rate (ORR) of 8.1% (3/37) and stable disease at 24 weeks in 14/37, for a disease control rate of 45.9%, and a median progression-free survival (mPFS) of 7.2 months in patients dosed at >120mg/d, with an ORR of 30% (3/10) and mPFS of 9.3 months in platinum-sensitive patients (PMID: 32694901; NCT03509636). 32694901