Shanghai: Wednesday, November 23, 2016: Hutchison MediPharma Limited (“HMP”) today announces that results from two non-small cell lung cancer (“NSCLC”) clinical studies will be presented at WCLC in Vienna, Austria, from December 4 to 7, 2016. Results from the positive Phase II third-line NSCLC clinical trial of fruquintinib, a highly selective and potent oral inhibitor of vascular endothelial growth factor receptors (“VEGFR”), will be detailed in an oral presentation. Results from the ongoing Phase Ib first-line NSCLC clinical trial of epitinib, a highly selective inhibitor of the epidermal growth factor receptor (“EGFR”) designed to optimize brain penetration, will also be presented.
In September 2015, HMP announced that the fruquintinib Phase II NSCLC clinical trial had successfully achieved its primary endpoint. The oral and poster presentations will include more mature data than those included in the following fruquintinib and epitinib study abstracts.
The results of the two studies will be presented in detail at WCLC as follows:
|Title:||A Randomized, Multi-Center, Double-Blind Phase II Study of Fruquintinib in Patients with Advanced Non-Small Cell Lung Cancer|
|Session:||OA11 – Angiogenesis in Advanced Lung Cancer, Oral Session|
|Date & Time:||Tuesday, December 6, 2016 (11:00 AM – 12:30 PM)|
|Title:||A Phase I Dose Expansion Study of Epitinib to Evaluate Efficacy and Safety in EGFR Mutation Positive (EGFRm+) NSCLC Patients with Brain Metastasis|
|Authors:||Qing Zhou, et al.|
|1st Session:||JCES01 Joint IASLC–Chinese Society for Clinical Oncology /Chinese Alliance Against Lung Cancer Session (ID 413)
|Date & Time:||Sunday, December 4, 2016 (10:30 AM – 11:30 AM)|
|2nd Session:||07. Advanced NSCLCP2.03b – Poster Session with Presenters Present (ID 465)
|Date & Time:||Tuesday, December 6, 2016 (2:30 PM – 3:45 PM)|
The WCLC presentations will be made available for download at www.chi-med.com/news on the following day.
Organized by the International Association for the Study of Lung Cancer (IASLC) and held annually, WCLC is a global, multidisciplinary scientific forum for sharing current knowledge and research progress in lung cancer. For more information, please visit: wclc2016.iaslc.com.
About NSCLC and TKIs to address EGFR-driven NSCLC
At an advanced stage, tumors secrete large amounts of vascular endothelial growth factors (“VEGF”), a protein ligand, to stimulate formation of excessive vasculature (angiogenesis) around the tumor in order to provide greater blood flow, oxygen, and nutrients to the tumor. VEGF and VEGFR play a pivotal role in tumor-related angiogenesis, and inhibition of the VEGF/VEGFR pathway. This represents an important therapeutic strategy in blocking the development of new blood vessels essential for tumors to grow and invade.
Every year, it is estimated that approximately 1.7 million new patients around the world are diagnosed with NSCLC, according to Frost & Sullivan. Lung cancer is the leading cause of cancer death among both men and women, accounting for about one-third of all cancer deaths, and more than breast, prostate and colorectal cancers combined. TKIs are used in many cancer therapies and act by blocking the cell signaling pathways that drive the growth of tumor cells. The very high prevalence of lung cancer in China as compared to the rest of the world is thought to be linked in part to the high incidence of cigarette smoking in the country. To date, several anti-VEGF/VEGFR agents have shown clinical efficacy against a number of tumor types. Given the scale and growth in the China oncology market, the market for VEGF/VEGFR inhibitors in China is expected to develop quickly in the next few years.
Patients who have the EGFRm+ form of NSCLC, which occurs in an estimated 10-15% of NSCLC patients in Europe and 30-40% of NSCLC patients in Asia, are particularly sensitive to treatment with currently available EGFR-TKIs. However, tumors almost always develop resistance to treatment leading to disease progression.
Brain metastasis has been identified in 10-30% EGFRm+ NSCLC patients at initial diagnosis and is one of the most devastating complications of lung cancer with poor life expectancy around 5-10 months. However, currently marketed EGFR-TKIs are unable to penetrate the blood-brain barrier with sufficient concentrations to provide clinical benefit in the brain, leaving the majority of patients with brain metastasis without an effective targeted therapy.
Fruquintinib (HMPL-013) is a highly selective small molecule drug candidate that has been shown to inhibit VEGFR 24 hours a day via an oral dose, without known off-target toxicities. It is currently under the joint development in China by HMP and its partner Eli Lilly and Company. Two late stage, pivotal Phase III registration studies are ongoing in lung cancer and colorectal cancer. In addition, fruquintinib is also in clinical development for gastric cancer.
Lung: The FALUCA trial is a randomized, double-blind, placebo-controlled, multi-center, Phase III registration study targeted at treating patients with advanced non-squamous NSCLC, who have failed two lines of systemic chemotherapy. Enrollment began in December 2015. Patients are randomized at a 2:1 ratio to receive either: 5mg of fruquintinib orally once per day, on a three-weeks-on / one-week-off cycle, plus BSC; or placebo plus BSC. The primary endpoint is OS, with secondary endpoints including PFS, ORR, DCR and duration of response. HMP plans to enroll approximately 520 patients in about 45 centers across China. Additional details about this study may be found at clinicaltrials.gov, using identifier NCT02691299.
Colorectal: The FRESCO trial is a randomized, double-blind, placebo-controlled, multicenter, Phase III pivotal trial in patients with locally advanced or metastatic colorectal cancer who have failed at least two prior systemic antineoplastic therapies, including fluoropyrimidine, oxaliplatin and irinotecan. Enrollment was completed in May 2016. 416 patients were randomized at a 2:1 ratio to receive either: 5mg of fruquintinib orally once per day, on a three-weeks-on / one-week-off cycle, plus BSC; or placebo plus BSC. The primary endpoint is OS, with secondary endpoints including PFS, objective response rate, disease control rate and duration of response. Once a pre-specified number of OS events (deaths) have occurred, data analysis will commence. Additional details of the FRESCO study may be found at clinicaltrials.gov, using identifier NCT02314819.
Gastric: HMP completed a Phase Ib dose finding study of fruquintinib in combination with paclitaxel, which established a combination regimen that was well tolerated. HMP continues to enroll patients in this Phase Ib to expand the data-set. Additional details about this study may be found at clinicaltrials.gov, using identifier NCT02415023.
EGFR inhibitors have revolutionized the treatment of NSCLC with EGFR activating mutations. However, existing EGFR inhibitors cannot penetrate the blood-brain barrier effectively, leaving the majority of patients with brain metastasis without an effective therapy. In contrast, epitinib (HMPL-813) is a potent and highly selective oral EGFR inhibitor designed to optimize brain penetration and has demonstrated brain penetration and efficacy in pre-clinical studies. Should epitinib be able to provide clinical benefit to NSCLC patients with brain metastasis, subject to regulatory approval, it may be well positioned to address a major global unmet medical need. Additional details about this study may be found at clinicaltrials.gov, using identifier NCT02590952.