A Novel Multi-Kinase Inhibitor for Combination Therapies

Vorolanib is a next-generation, small-molecule, multi-kinase inhibitor designed for combination therapies1

  • Vorolanib is a highly potent, orally administered compound that provides intermittent inhibition of angiogenesis with once-daily dosing1
  • As monotherapy, vorolanib was well tolerated, with promising efficacy in a phase 1 trial in patients with advanced solid tumors (n = 59)1
    • Vorolanib showed a short half-life (≤ 8.5 hours), and no drug accumulation was observed after 21 days of dosing1
    • Vorolanib had a safety profile consistent with that of an angiogenesis inhibitor. The most common treatment-related adverse events were fatigue (29%), nausea (23%), and diarrhea (21%), mostly low grade; the most common grade 3 adverse event was proteinuria (4%)
  • Vorolanib has demonstrated promising safety and efficacy in combination with everolimus in a phase 1 study in patients with advanced renal cell cancer (RCC) in China2
  • Trials of vorolanib in combination with immuno-oncology agents in solid tumors, including non-small cell lung cancer, small cell lung cancer, melanoma, thymic carcinoma, and RCC, are ongoing
Vorolanib MOA diagram

MOA, mechanism of action; mTOR, mechanistic target of rapamycin; PD-1, programmed cell death 1; PI3K, phosphoinositide 3-kinase; PDGFR, platelet-derived growth factor receptor; RAS, RAF, MEK, ERK, mitogen-activated protein kinase pathway; VEGFR, vascular endothelial growth factor receptor.

References

  1. Bendell JC, et al. Oncologist. 2019;24:455-e121.
  2. Sheng X, et al. J Clin Oncol. 2017;35(15 suppl) [abstract 4575].

Clinical Trials

Vorolanib pipeline

IO, immuno-oncology; NSCLC, non-small cell lung cancer; PD-1, programmed cell death 1; RCC, renal cell carcinoma; SCLC, small cell lung cancer.

NCT03095040: This randomized, double blind, phase 2/3 study aims to evaluate the efficacy and safety of vorolanib in combination with everolimus in Chinese patients with advanced renal cell carcinoma.

NCT03602547: This is a phase 2 clinical study of vorolanib combined with JS001 (anti–PD-1) in the treatment of advanced mucosal melanoma.

NCT03583086: This is a phase 1/2 study to evaluate the safety and preliminary activity of nivolumab in combination with vorolanib in patients with refractory thoracic tumors.

NCT03511222: This is a phase Ib trial of vorolanib combined with checkpoint inhibitors (nivolumab and pembrolizumab) in patients with solid tumors.

 

For more information on vorolanib clinical trials, please contact .

Publications and Abstracts

Bendell JC, Patel MR, Moore KN, Chua CC, Arkenau H-T, Dukart G, Harrow K, Liang C.

Phase I, first-in-human, dose-escalation study to evaluate the safety, tolerability, and pharmacokinetics of vorolanib in patients with advanced solid tumors. Oncologist. 2019;24(4):455.e121.

Scarpelli M, Rampurwala M, Eickhoff J, Carmichael L, Heideman J, Binger K, Kolesar J, Perlman S, Harrow K, Dukart G, Liang C, Jeraj R, Liu G, Bruce JY.

Pharmacodynamic study using FLT PET/CT in advanced solid malignancies treated with a sequential combination of X-82 and docetaxel. Cancer Chemother Pharmacol. 2018;82(2):211-219.

2019 AACR Annual Meeting
March 29-April 3, 2019; Atlanta, GA

Whisenant JG, Beckerman K, Borghaei H, Owonikoko T, Patel J, Shyr Y, Harrow K, Liang C, Holzhausen A, Wakelee H, Horn L.

Phase I/II study to evaluate the safety and preliminary activity of nivolumab in combination with vorolanib in patients with refractory thoracic tumors. Presented at: AACR Annual Meeting 2019; March 29-April 3, 2019; Atlanta, GA [abstract CT171/15].

2019 ASCO Gastrointestinal Cancers Symposium
January 17-19, 2019; San Francisco, CA

Bagegni NA, Tan BR, Park H, Kraft K, Amin MA, Lim K-H, Morgensztern D, Pedersen K, Suresh R, Trikalinos N, Wang-Gillam A.

A phase Ib trial of anti-VEGFR/PDGFR vorolanib combined with immune checkpoint inhibitors (CPIs) in solid tumors. J Clin Oncol. 2019;37(4 suppl) [abstract TPS472].

2018 ASCO Annual Meeting
June 1-5, 2018; Chicago, IL

Song Y, Wang J, Zhou A-P, Zhang W, Liang C, Yang L.

Vorolanib (CM082) in Chinese patients with advanced solid tumor: a phase 1, open-label, dose escalation study. J Clin Oncol. 2018;36(15 suppl) [abstract 2580].

Guo J, Sheng X, Ye D, He Z, Zhou A-P, Yao X, Wang Z, Shi B, Tu X, Zhang Y, He C, Fu C, Ji Z, Yang B, Wu B, Qin S, Hu Z, Zhou F-J, Guo J, Tan F.

Vorolanib (CM082), everolimus, and the combination in patients with pretreated metastatic renal cell carcinoma (CONCEPT study): a randomized, phase 2/3, double-blind, multi-center trial. J Clin Oncol. 2018;36(15 suppl) [abstract TPS4605].

20th Annual Meeting of Chinese Society of Clinical Oncology
September 26-30, 2017; Xiamen, China

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

Anti-VEGFR, PDGFR, and CSF1R tyrosine kinase inhibitor CM082 (X-82) in combination with everolimus for treatment of metastatic renal cell carcinoma: a phase 1 clinical trial. Lancet Oncol. 2017;18(special issue) [abstract S8].

2017 ASCO Annual Meeting
June 2-6, 2017; Chicago, IL

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

A phase I clinical trial of CM082 (X-82) in combination with everolimus for treatment of metastatic renal cell carcinoma. J Clin Oncol. 2017;35(15 suppl) [abstract 4575].

2016 ASCO Annual Meeting
June 3-7, 2016; Chicago, IL

Tan BR, Picus J, Chan E, Lockhart AC, Roth BJ, Morton A, Liang C, Wang-Gillam A.

Phase I study of X-82, an oral dual anti-VEGFR/PDGFR tyrosine kinase inhibitor, with everolimus in solid tumors. J Clin Oncol. 2016;34(15 suppl) [abstract 2588].

2015 ASCO Annual Meeting
May 29-June 2, 2015; Chicago, IL

Rampurwala MM, Carmichael L, Eickhoff JC, Kolesar J, Binger K, Heideman J, Perlman S, Liang C, Jeraj R, Liu G, Bruce JY.

Pharmacodynamic study using FLT PET/CT in advanced solid malignancies treated with a sequential combination of X-82 and docetaxel. J Clin Oncol. 2015;33(15 suppl) [abstract TPS2601].