Missing content? – Request curation!
Request curation for specific Genes, variants, or PubMed publications.
Have questions, comments or suggestions? - Let us know!
Email us at : firstname.lastname@example.org
|Ref Type||Journal Article|
|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|
|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.|
|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|