Reference Detail

Ref Type

Journal Article

PMID

(32335374)

Authors

Sheng X, Yan X, Chi Z, Cui C, Si L, Tang B, Li S, Mao L, Lian B, Wang X, Bai X, Zhou L, Kong Y, Dai J, Ding L, Mao L, Guo J

Title

Phase 1 trial of vorolanib (CM082) in combination with everolimus in patients with advanced clear-cell renal cell carcinoma.

Journal	Vol	Issue	Date	Pages	Journal Short Title
EBioMedicine	55		2020 May	102755	EBioMedicine

URL

Abstract Text

Vorolanib (X-82, CM082) is a multi-target tyrosine kinase inhibitor. This study aimed to evaluate the tolerability, safety, pharmacokinetics and antitumor activities of vorolanib plus everolimus (an inhibitor of mammalian target of rapamycin).Patients had histologically or cytologically confirmed advanced RCC and failed with standard therapy were eligible for this study. Dose-escalated combinations of vorolanib (100, 150 or 200 mg once daily) with everolimus (5 mg once daily) were administered on 28-day cycles until disease progression or unacceptable toxicity using a conventional 3 + 3 dose-escalation design.22 patients (100 mg n = 4, 150 mg n = 3, 200 mg n = 15) were enrolled. Only one patient experienced dose-limiting toxicity (DLT, grade 4 thrombocytopenia) in the vorolanib 200 mg combination cohort, and the maximum tolerated dose (MTD) was not reached. The most common treatment-related adverse events were proteinuria (100%), leukopenia (77%), hypercholesterolaemia (77%), increased low-density lipoprotein (68%), hypertriglyceridaemia (64%), hyperglycaemia (59%), and fatigue (55%). Most treatment-related adverse events were grade 1 to 2, with grade 3 or higher toxicities mostly seen in the 200 mg cohort. Single dosing of vorolanib demonstrated dose-proportional increases in the Cmax and AUC, and observed short t1/2z ranging from 4.74±1.44 to 12.89±7.49 h. The pharmacokinetic parameters for everolimus were similar among all cohorts. Of 19 evaluable patients, the ORR and DCR was 32% (n = 6, 95% CI, 13-57%) and 100% (95% CI, 82-100%), respectively.Combination therapy of vorolanib 200 mg plus everolimus 5 mg once daily is potentially effective with potential activity. Further evaluation of the combination in advanced RCC patients is ongoing (NCT03095040).Betta Pharmaceutical Co., Ltd., Hangzhou, China.

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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
Vorolanib	Vorolanib	0	1

Drug Name	Trade Name	Synonyms	Drug Classes	Drug Description
Vorolanib		X-82\|CM-082\|CM082	PDGFR Inhibitor (Pan) 30 VEGFR Inhibitor (Pan) 36	Vorolanib (X-82) is a dual VEGFR/PDGFR inhibitor, which inhibits tumor angiogenesis and cell proliferation in tumors (PMID: 32335374, PMID: 30478190).

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