Reference Detail

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	Vol	Issue	Date	Pages	Journal Short Title
Chinese journal of cancer research = Chung-kuo yen cheng yen chiu	32	3	2020 Jun	370-382	Chin J Cancer Res

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
Fluzoparib	Fluzoparib	1	0

Drug Name	Trade Name	Synonyms	Drug Classes	Drug Description
Fluzoparib		HS10160\|SHR-3162\|SHR3162\|Fuzuloparib	PARP Inhibitor (Pan) 30	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