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A Phase I/II Trial of Fruquintinib in Combination with Paclitaxel for Second-line Treatment in Patients with Advanced Gastric Cancer
Ruihua Xu, Dongsheng Zhang, Lin Shen, Jin Li, Jing Huang, Yang Zhang, Jifang Gong, Weijian Guo, Songhua Fan, Ke Li, Ye Hua and Weiguo Su
Event: ASCO GI
Title: A Phase I/II Trial of Fruquintinib in Combination with Paclitaxel for Second-line Treatment in Patients with Advanced Gastric Cancer
Abstract number: 128
Session: Poster Session A: Cancers of the Esophagus and Stomach
Date & Time: Thursday, January 19, 2017, 12:30 PM-6:30 PM (PST)
Safety and efficacy of fruquintinib in patients with previously treated metastatic colorectal cancer: a phase Ib study and a randomized double-blind phase II study
Authors: Rui-Hua Xu, Jin Li, Yuxian Bai, Jianming Xu, Tianshu Liu, Lin Shen, Liwei Wang, Hongming Pan, Junning Cao, Dongsheng Zhang, Songhua Fan, Ye Hua and Weiguo Su
Citation: Journal of Hematology & Oncology 2017 Jan 19; 10(1):22
DOI: 10.1186/s13045-016-0384-9
PubMed ID: 28103904
Background: To assess the efficacy and safety of fruquintinib, a vascular endothelial growth factor receptor (VEGFR) inhibitor, in metastatic colorectal cancer (mCRC) patients.
Methods: A phase Ib open-label study and phase II randomized, placebo-controlled trial compared the efficacy of fruquintinib plus best supportive care (BSC) with placebo plus BSC in mCRC patients with ≥2 lines of prior therapies. The primary endpoint was progression-free survival (PFS).
Results: In the phase Ib study, 42 patients took fruquintinib 5 mg for 3 weeks on/1 week off. The median PFS was 5.80 months, and the median overall survival (OS) was 8.88 months. In the phase II study, 71 patients were randomized (47 to fruquintinib, 24 to placebo). PFS was significantly improved with fruquintinib plus BSC (4.73 months; 95% confidence interval [CI] 2.86–5.59) versus placebo plus BSC (0.99 months; 95% CI 0.95–1.58); (hazard ratio [HR] 0.30; 95% CI 0.15–0.59; P < 0.001). The median OS was 7.72 versus 5.52 months (HR 0.71; 95% CI 0.38–1.34). The most common grade 3–4 adverse events were hypertension and hand-foot skin reaction.
Conclusions: Fruquintinib showed a significant PFS benefit of 3.7 months in patients with treatment-refractory mCRC. The safety profile was consistent with that of VEGFR tyrosine kinase inhibitors. A randomized phase III confirmatory study in mCRC is underway.
Trial registration: NCT01975077 and NCT02196688
Intercontinental Barclay, New York, NY
Change of Directors
London: Monday, January 16, 2017: Hutchison China MediTech Limited (“Chi-Med”) (AIM/Nasdaq: HCM) today announces with effect from February 1, 2017, Mr Paul Rutherford Carter has been appointed as Senior Independent Non-Executive Director and member of the Audit Committee, Remuneration Committee and Technical Committee of Chi-Med; and Mr Shigeru Endo tendered his resignation as Non-executive Director and Mr Christopher Nash tendered his resignation as Senior Independent Non-executive Director and member of Audit Committee and Remuneration Committee effective on the same date.
Mr Carter, aged 56, has more than 25 years of experience in the pharmaceutical industry. From 2006 to 2016, Mr Carter served in various senior executive roles at Gilead Sciences, Inc. (“Gilead”), a research-based biopharmaceutical company, with the last position as Executive Vice President, Commercial Operations. In this role Mr Carter headed the worldwide commercial organization responsible for the launch and commercialization of all of Gilead’s products. Prior to joining Gilead, he spent 14 years with GlaxoSmithKline PLC (GSK) and its group companies, with the last position as a Regional Head of the International business in Asia.
Mr Carter is currently a director of Alder Biopharmaceuticals, Inc. He was previously a director of Gilead Sciences Ltd, Gilead Sciences International Ltd. and Gilead Sciences Europe Ltd. within the past five years.
Mr Carter holds a degree in Business Studies from the Ealing School of Business and Management (now merged into University of West London) and is a Fellow of the Chartered Institute of Management Accountants in the UK.
He does not have any shareholdings in Chi-Med. Save for the information disclosed above, there is no other information in relation to Mr Carter that is required to be disclosed pursuant to Rule 17 and Schedule 2(g) of the AIM Rules for Companies.
Mr Simon To, Chairman of Chi-Med said “We thank Mr Shigeru Endo and Mr Christopher Nash for their invaluable contributions to the Company during their tenure and welcome Mr Carter to the Board whose experience in the global biopharmaceutical industry will be important to the Company.”
About Chi-Med
Chi-Med is an innovative biopharmaceutical company which researches, develops, manufactures and sells pharmaceuticals and healthcare products. Its Innovation Platform, Hutchison MediPharma Limited, focuses on discovering and developing innovative therapeutics in oncology and autoimmune diseases for the global market. Its Commercial Platform manufactures, markets, and distributes prescription drugs and consumer health products in China.
Chi-Med is majority owned by the multinational conglomerate CK Hutchison Holdings Limited (SEHK: 0001). For more information, please visit: www.chi-med.com.
Forward-Looking Statements
This announcement contains forward-looking statements within the meaning of the “safe harbor” provisions of the U.S. Private Securities Litigation Reform Act of 1995. These forward-looking statements reflect Chi-Med’s current expectations regarding future events. Forward-looking statements involve risks and uncertainties. Such risks and uncertainties include, among other things, the risk that current or future appointees to Chi-Med’s board of directors are not effective in their respective positions, the difficulty in locating and recruiting suitable candidates for its board of directors and the management difficulties which may arise from changes in Chi-Med’s board of directors. Existing and prospective investors are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date hereof. For further discussion of these and other risks, see Chi-Med’s filings with the U.S. Securities and Exchange Commission and on AIM. Chi-Med undertakes no obligation to update or revise the information contained in this announcement, whether as a result of new information, future events or circumstances or otherwise.
Contacts
| Investor Enquiries | ||
| Christian Hogg, CEO | +852 2121 8200 | |
| International Media Enquiries | ||
| Anthony Carlisle, Citigate Dewe Rogerson | +44 7973 611 888 (Mobile) | anthony.carlisle@cdrconsultancy.co.uk |
| U.S. Based Media Enquiries | ||
| Brad Miles, BMC Communications | +1 (917) 570 7340 (Mobile) | bmiles@bmccommunications.com |
| Susan Duffy, BMC Communications | +1 (917) 499 8887 (Mobile) | sduffy@bmccommunications.com |
| Investor Relations | ||
| Matt Beck, The Trout Group | +1 (917) 415 1750 (Mobile) | mbeck@troutgroup.com |
| David Dible, Citigate Dewe Rogerson | +44 7967 566 919 (Mobile) | david.dible@citigatedr.co.uk |
| Panmure Gordon (UK) Limited | ||
| Richard Gray / Andrew Potts | +44 (20) 7886 2500 |
London: Monday, January 16, 2017: Hutchison China MediTech Limited (“Chi-Med”) (AIM/Nasdaq:HCM) today announces that it has initiated a Phase II study of a combination therapy using fruquintinib and Iressa® in the first-line setting for patients with advanced or metastatic non-small cell lung cancer (“NSCLC”) in China. Fruquintinib is a highly selective and potent oral inhibitor of vascular endothelial growth factor receptors (“VEGFR”). The first drug dose was administered on January 9, 2017.
This Phase II combination therapy study is a multi-center, single-arm, open-label study. The objectives are to evaluate the safety and tolerability as well as preliminary efficacy of the combination therapy in the first-line setting for advanced or metastatic non-squamous NSCLC patients with epidermal growth factor receptor (“EGFR”) activating mutations. Treatment will be continued until disease progression or intolerable toxicity occurs. Additional details about this study may be found at clinicaltrials.gov, using identifier NCT02976116.
About NSCLC and Tyrosine Kinase Inhibitors (“TKIs”) to address EGFR-driven NSCLC
At an advanced stage, tumors secrete large amounts of vascular endothelial growth factors (“VEGF”), which are protein ligandsthat 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. Inhibition of the VEGF/VEGFR pathway 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-quarter of all cancer deaths (American Cancer Society), and more than breast, prostate and colorectal cancers combined.
NSCLC patients with EGFR activating mutations, which are an estimated 10-15% of NSCLC patients in the United States and 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. Combining therapies that inhibit different signaling pathways has the potential to be more effective than inhibition of a single pathway and to overcome tumor resistance.
About Fruquintinib
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 Chi-Med and its partner Eli Lilly and Company. Two late-stage, pivotal Phase III registration studies are ongoing in colorectal cancer (FRESCO) and lung cancer (FALUCA). In addition, fruquintinib is also in clinical development for gastric cancer.
Colorectal: The FRESCO trial is a randomized, double-blind, placebo-controlled, multi-center, 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: 5 mg of fruquintinib orally once per day, on a three-weeks-on / one-week-off cycle, plus best supportive care (“BSC”); or placebo plus BSC. The primary endpoint is overall survival (“OS”), with secondary endpoints including progression free survival (“PFS”), objective response rate, disease control rate and duration of response. Additional details of the FRESCO study may be found at clinicaltrials.gov, using identifier NCT02314819.
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: 5 mg 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. Chi-Med plans to enroll approximately 520 patients in about 45 centers across China. Additional details about FALUCA study may be found at clinicaltrials.gov, using identifier NCT02691299.
Gastric: Chi-Med completed a Phase Ib dose finding study of fruquintinib in combination with paclitaxel, which established a combination regimen that was well tolerated. Additional details about this study may be found at clinicaltrials.gov, using identifier NCT02415023.
About Iressa®, an EGFR-TKI
Iressa® (gefitinib) is a targeted monotherapy developed by AstraZeneca for the treatment of patients with advanced or metastatic EGFR activating mutation positive NSCLC. Iressa® acts by inhibiting the tyrosine kinase enzyme in the EGFR, thus blocking the transmission of signals involved in the growth and spread of tumors. Iressa® is approved in 91 countries worldwide.
About Chi-Med
Chi-Med is an innovative biopharmaceutical company which researches, develops, manufactures and sells pharmaceuticals and healthcare products. Its Innovation Platform, Hutchison MediPharma Limited, focuses on discovering and developing innovative therapeutics in oncology and autoimmune diseases for the global market. Its Commercial Platform manufactures, markets, and distributes prescription drugs and consumer health products in China.
Chi-Med is majority owned by the multinational conglomerate CK Hutchison Holdings Limited (SEHK: 0001). For more information, please visit: www.chi-med.com.
Forward-Looking Statements
This press release contains forward-looking statements within the meaning of the “safe harbor” provisions of the U.S. Private Securities Litigation Reform Act of 1995. These forward-looking statements reflect Chi-Med’s current expectations regarding future events, including its expectations for the clinical development of fruquintinib, plans to initiate clinical studies for fruquintinib, its expectations as to whether such studies would meet their primary or secondary endpoints, and its expectations as to the timing of the completion and the release of results from such studies. Forward-looking statements involve risks and uncertainties. Such risks and uncertainties include, among other things, assumptions regarding enrollment rates, timing and availability of subjects meeting a study’s inclusion and exclusion criteria, changes to clinical protocols or regulatory requirements, unexpected adverse events or safety issues, the ability of drug candidate fruquintinib to meet the primary or secondary endpoint of a study, to obtain regulatory approval in different jurisdictions, to gain commercial acceptance after obtaining regulatory approval, the potential market of fruquintinib for a targeted indication and the sufficiency of funding. In addition, as certain studies rely on the use of Iressa® as a combination therapeutic with fruquintinib, such risks and uncertainties include assumptions regarding the safety, efficacy, supply and continued regulatory approval of Iressa®. Existing and prospective investors are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date hereof. For further discussion of these and other risks, see Chi-Med’s filings with the U.S. Securities and Exchange Commission and on AIM. Chi-Med undertakes no obligation to update or revise the information contained in this press release, whether as a result of new information, future events or circumstances or otherwise.
Contacts
| Investor Enquiries | ||
| Christian Hogg, CEO | +852 2121 8200 | |
| International Media Enquiries | ||
| Anthony Carlisle, Citigate Dewe Rogerson | +44 7973 611 888 (Mobile) | anthony.carlisle@cdrconsultancy.co.uk |
| U.S. Based Media Enquiries | ||
| Brad Miles, BMC Communications | +1 (917) 570 7340 (Mobile) | bmiles@bmccommunications.com |
| Susan Duffy, BMC Communications | +1 (917) 499 8887 (Mobile) | sduffy@bmccommunications.com |
| Investor Relations | ||
| Matt Beck, The Trout Group | +1 (917) 415 1750 (Mobile) | mbeck@troutgroup.com |
| David Dible, Citigate Dewe Rogerson | +44 7967 566 919 (Mobile) | david.dible@citigatedr.co.uk |
| Panmure Gordon (UK) Limited | ||
| Richard Gray / Andrew Potts | +44 (20) 7886 2500 |
London: Monday, January 16, 2017: Hutchison China MediTech Limited (“Chi-Med”) (AIM/Nasdaq: HCM) today announces that it has initiated a Phase II study of sulfatinib in second-line biliary tract cancer (“BTC”) patients in China. Sulfatinib is an oral, novel angio-immunokinase inhibitor that selectively targets vascular endothelial growth factor receptor (“VEGFR”), fibroblast growth factor receptor (“FGFR”) and colony-stimulating factor-1 receptor (“CSF-1R”), three key tyrosine kinase receptors involved in tumor angiogenesis and immune evasion. The first drug dose was administered on January 9, 2017.
This Phase II study is a multi-center, single-arm, open-label study to evaluate the efficacy and safety of sulfatinib as a monotherapy in treating advanced or metastatic BTC patients who failed one prior systemic therapy. The primary endpoint is progression free survival (“PFS”) at 16 weeks, with secondary endpoints including objective response rate (“ORR”), disease control rate (“DCR”), duration of response, PFS, overall survival (“OS”) and safety. Additional details about this study may be found at clinicaltrials.gov, using identifier NCT02966821.
About BTC
BTC, also known as cholangiocarcinoma, is a heterogeneous group of rare but fatal malignancies arising from the biliary tract epithelia, including intrahepatic cholangiocarcinoma and extrahepatic cholangiocarcinoma. BTC is the second most frequently occurring type of liver cancer in the world, after hepatocellular carcinoma (HCC), accounting for approximately 15% of all liver cancer cases[1]. In 2017, there will be approximately 18,000 new BTC cases in the United States, according to the National Cancer Institute. However, in China, the incidence can be up to 40 times the rate observed in the Western world[2].
Gemcitabine is the current first-line therapy for BTC patients, either as a monotherapy or in combination with cisplatin, and there is no established second-line therapy for this fatal disease worldwide. The median life expectancy is less than 12 months for patients with unresectable or metastatic disease at diagnosis. Accordingly, we see a high unmet medical need for new targeted treatment options.
About Sulfatinib
Sulfatinib is an oral, novel angio-immunokinase inhibitor that selectively inhibits the tyrosine kinase activity associated with VEGFR, FGFR and CSF-1R, three key tyrosine kinase receptors involved in tumor angiogenesis and immune evasion. Inhibition of the VEGFR signaling pathway can act to stop angiogenesis, the growth of the vasculature around the tumor, and thereby starve the tumor of the nutrients and oxygen it needs to grow rapidly. Aberrant activation of the FGFR signaling pathway, which can be increased by anti-VEGFR therapy treatment, is shown to be associated with cancer progression by promoting tumor growth, angiogenesis and formation of the myeloid derived suppressor cells. Inhibition of the CSF-1R signaling pathway blocks the activation of tumor-associated macrophages, which are involved in suppressing immune responses against tumors.
In addition to the BTC trial, six sulfatinib clinical trials are underway in China and the United States, including two Phase III studies in neuroendocrine tumor patients (SANET-p and SANET-ep) and a Phase II study in thyroid cancer patients.
The SANET-p trial is a randomized, double-blind, placebo-controlled, multi-center, Phase III pivotal registration trial to treat about 190 pathologically low or intermediate grade pancreatic NET patients in China whose disease has progressed, locally advanced or distant metastasized and for whom there is no effective therapy. The primary endpoint is PFS, with secondary endpoints including ORR, DCR, duration of response, time to response and OS. Additional details of the SANET-p study may be found at clinicaltrials.gov, using identifier NCT02589821. The SANET-ep trial is similar to the SANET-p trial and is targeted at treating about 270 non-pancreatic NET patients in China. Additional details of the SANET-ep study may be found at clinicaltrials.gov, using identifier NCT02588170.
Chi-Med is conducting an open-label Phase II clinical trial to evaluate the efficacy and safety of sulfatinib in about 50 patients with locally advanced or metastatic radioactive iodine-refractory differentiated thyroid cancer or medullary thyroid cancer in China. The primary endpoint is ORR, with secondary endpoints including the safety and tolerability, DCR, time to response and PFS. Additional details of this study may be found at clinicaltrials.gov, using identifier NCT02614495.
[1] A Ananthakrishnan et al; Epidemiology of Primary and Secondary Liver Cancers; Semin Intervent Radiol. 2006 Mar; 23(1): 47–63.
[2] JA Bridgewater et al; Biliary Tract Cancer: Epidemiology, Radiotherapy, and Molecular Profiling; Am Soc Clin Oncol Educ Book. 2016;35:e194-203.
About Chi-Med
Chi-Med is an innovative biopharmaceutical company which researches, develops, manufactures and sells pharmaceuticals and healthcare products. Its Innovation Platform, Hutchison MediPharma Limited, focuses on discovering and developing innovative therapeutics in oncology and autoimmune diseases for the global market. Its Commercial Platform manufactures, markets, and distributes prescription drugs and consumer health products in China.
Chi-Med is majority owned by the multinational conglomerate CK Hutchison Holdings Limited (SEHK: 0001). For more information, please visit: www.chi-med.com.
Forward-Looking Statements
This press release contains forward-looking statements within the meaning of the “safe harbor” provisions of the U.S. Private Securities Litigation Reform Act of 1995. These forward-looking statements reflect Chi-Med’s current expectations regarding future events, including its expectations for the clinical development of sulfatinib, plans to initiate clinical studies for sulfatinib, its expectations as to whether such studies would meet their primary or secondary endpoints, and its expectations as to the timing of the completion and the release of results from such studies. Forward-looking statements involve risks and uncertainties. Such risks and uncertainties include, among other things, assumptions regarding enrollment rates, timing and availability of subjects meeting a study’s inclusion and exclusion criteria, changes to clinical protocols or regulatory requirements, unexpected adverse events or safety issues, the ability of drug candidate sulfatinib to meet the primary or secondary endpoint of a study, to obtain regulatory approval in different jurisdictions, to gain commercial acceptance after obtaining regulatory approval, the potential market of sulfatinib for a targeted indication and the sufficiency of funding. Existing and prospective investors are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date hereof. For further discussion of these and other risks, see Chi-Med’s filings with the U.S. Securities and Exchange Commission and on AIM. Chi-Med undertakes no obligation to update or revise the information contained in this press release, whether as a result of new information, future events or circumstances or otherwise.
Contacts
| Investor Enquiries | ||
| Christian Hogg, CEO | +852 2121 8200 | |
| International Media Enquiries | ||
| Anthony Carlisle, Citigate Dewe Rogerson | +44 7973 611 888 (Mobile) | anthony.carlisle@cdrconsultancy.co.uk |
| U.S. Based Media Enquiries | ||
| Brad Miles, BMC Communications | +1 (917) 570 7340 (Mobile) | bmiles@bmccommunications.com |
| Susan Duffy, BMC Communications | +1 (917) 499 8887 (Mobile) | sduffy@bmccommunications.com |
| Investor Relations | ||
| Matt Beck, The Trout Group | +1 (917) 415 1750 (Mobile) | mbeck@troutgroup.com |
| David Dible, Citigate Dewe Rogerson | +44 7967 566 919 (Mobile) | david.dible@citigatedr.co.uk |
| Panmure Gordon (UK) Limited | ||
| Richard Gray / Andrew Potts | +44 (20) 7886 2500 |
London: Monday, January 16, 2017: Hutchison China MediTech Limited (“Chi-Med”) (AIM/Nasdaq: HCM) today announces that data from the ongoing Phase I/II clinical trial of fruquintinib in combination with paclitaxel (Taxol®) in second-line patients with advanced gastric cancer will be presented at the 2017 Gastrointestinal Cancers Symposium sponsored by the American Society of Clinical Oncology (“ASCO-GI”), being held in San Francisco, California from January 19 to 21, 2017. Fruquintinib is a highly selective and potent oral inhibitor of vascular endothelial growth factor receptors (“VEGFR”).
Chi-Med completed a Phase Ib dose finding study of fruquintinib in combination with paclitaxel, which established a combination regimen that was well tolerated, and continued to enroll patients in this trial to expand the data-set. Additional details about this study may be found at clinicaltrials.gov, using identifier NCT02415023.
The most recent results of the study will be presented in detail as follows:
| Presentation Title: |
A Phase I/II trial of Fruquintinib in Combination with Paclitaxel for Second-line Treatment in Patients with Advanced Gastric Cancer
|
| Authors: |
Ruihua Xu, Dongsheng Zhang, Lin Shen, Jin Li, Jing Huang, Yang Zhang, Jifang Gong, Weijian Guo, Songhua Fan, Ke Li, Ye Hua and Weiguo Su
|
| Abstract No: |
128
|
| Session: |
Poster Session A: Cancers of the Esophagus and Stomach
|
| Date & Time: | Thursday, January 19, 2017, 12:30 PM-6:30 PM (PST) |
Once presented, the presentation will be available at www.chi-med.com/news. Further information about ASCO-GI is available at gicasym.org.
ABSTRACT
A Phase I/II Trial of Fruquintinib in Combination with Paclitaxel for Second-line Treatment in Patients with Advanced Gastric Cancer
Ruihua Xu, Dongsheng Zhang, Lin Shen, Jin Li, Jing Huang, Yang Zhang, Jifang Gong, Weijian Guo, Songhua Fan, Ke Li, Ye Hua and Weiguo Su
Background
Advanced gastric cancer is a major public health problem, particularly in Asian countries. The treatment options are limited in patients who failed standard first-line chemotherapy. This Phase I/II study is aimed to evaluate the tolerability, pharmacokinetics (“PK”) and preliminary efficacy of fruquintinib, a selective oral VEGFR inhibitor, combined with paclitaxel as second-line therapy in Chinese patients with advanced gastric cancer.
Patients and methods
This open arm Phase I/II trial (NCT02415023) consisted of dose finding and dose expansion stages. In the dose finding stage, three dose levels of fruquintinib (2, 3, 4mg once daily; three-weeks-on and one-week-off) were evaluated in combination with standard 80mg/m2 paclitaxel (once weekly on day 1, 8 and 15) in a 28-day cycle until the maximum tolerated dose (“MTD”) or recommended phase II dose (“RP2D”) was reached. Additional patients were enrolled at dose expansion phase with fruquintinib RP2D regimen to assess further the efficacy, safety and PK profile.
Results
As of September 10, 2016, a total of 32 patients were enrolled and dosed with fruquintinib in combination with weekly paclitaxel. The RP2D of fruquintinib was determined to be 4 mg daily.
Two patients at 4 mg experienced dose-limiting toxicity, both with febrile neutropenia. Grade 3 or 4 treatment emergent adverse events (“TEAE”) were neutropenia (40.6%), leukopenia (28.1%), decreased hemoglobin (6.25%), hand-foot skin reaction (6.25%), neurophlegmon (6.25%), and hypertension (6.25%), with higher frequencies in the 4mg cohort as compared with lower doses.
At steady state, fruquintinib drug exposure, i.e. the area under the curve (AUCss), increased dose-proportionally and was within the same range as given as a single agent. Paclitaxel exposure at fruquintinib RP2D (4mg) however, increased by approximately 30% as compared to that of single agent.
28 of 32 patients were evaluable for tumor response, and of these, 10 patients achieved confirmed partial response (objective response rate, (“ORR”) = 35.7%), 9 patients experienced stable disease for at least 8 weeks (disease control rate, (“DCR”) = 67.9%). At fruquintinib RP2D, ≥16w progression free survival (“PFS”) = 50% and ≥7m overall survival (“OS”) = 50%.
Conclusion
Combination therapy of fruquintinib and paclitaxel appeared to be generally well-tolerated with promising tumor response in the second-line setting in advanced gastric cancer. Further evaluation of fruquintinib in a randomized control trial is warranted.
About Gastric Cancer
Every year, it is estimated that approximately one million new patients around the world are diagnosed with gastric cancer, according to Frost & Sullivan, and in 2015 China represented approximately 44% of all newly diagnosed gastric cancer cases worldwide. The very high prevalence of gastric cancer in China as compared to the rest of the world is thought to be linked in part to food preparation habits, such as the use of certain preservatives. In 2015 there were an estimated 679,100 incidence gastric cancer cases and 498,000 mortality cases in China, according to the National Central Cancer Registry of China.
Gastric cancer is the third of most lethal cancer worldwide. As it is often diagnosed at an advanced stage, prognosis is poor with a median OS of less than 12 months. Although targeted therapy is under development in China, chemotherapy remains the mainstay of treatment for gastric cancer patients and confers only a moderate survival advantage. Accordingly, we see a high medical need for new targeted treatment options.
About Fruquintinib
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 Chi-Med and its partner Eli Lilly and Company. Two late-stage, pivotal Phase III registration studies are ongoing in colorectal cancer (FRESCO) and lung cancer (FALUCA) along with the currently reported gastric cancer trial.
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 best supportive care (“BSC”); or placebo plus BSC. The primary endpoint is OS, with secondary endpoints including PFS, ORR, DCR and duration of response. Additional details of the FRESCO study may be found at clinicaltrials.gov, using identifier NCT02314819.
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. Chi-Med 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.
About Chi-Med
Chi-Med is an innovative biopharmaceutical company which researches, develops, manufactures and sells pharmaceuticals and healthcare products. Its Innovation Platform, Hutchison MediPharma Limited, focuses on discovering and developing innovative therapeutics in oncology and autoimmune diseases for the global market. Its Commercial Platform manufactures, markets, and distributes prescription drugs and consumer health products in China.
Chi-Med is majority owned by the multinational conglomerate CK Hutchison Holdings Limited (SEHK: 0001). For more information, please visit: www.chi-med.com.
Forward-Looking Statements
This press release contains forward-looking statements within the meaning of the “safe harbor” provisions of the U.S. Private Securities Litigation Reform Act of 1995. These forward-looking statements reflect Chi-Med’s current expectations regarding future events, including its expectations for the clinical development of fruquintinib, plans to initiate clinical studies for fruquintinib, its expectations as to whether such studies would meet their primary or secondary endpoints, and its expectations as to the timing of the completion and the release of results from such studies. Forward-looking statements involve risks and uncertainties. Such risks and uncertainties include, among other things, assumptions regarding enrollment rates, timing and availability of subjects meeting a study’s inclusion and exclusion criteria, changes to clinical protocols or regulatory requirements, unexpected adverse events or safety issues, the ability of drug candidate fruquintinib to meet the primary or secondary endpoint of a study, to obtain regulatory approval in different jurisdictions, to gain commercial acceptance after obtaining regulatory approval, the potential market of fruquintinib for a targeted indication and the sufficiency of funding. In addition, as certain studies rely on the use of paclitaxel as a combination therapeutic with fruquintinib, such risks and uncertainties include assumptions regarding the safety, efficacy, supply and continued regulatory approval of paclitaxel. Existing and prospective investors are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date hereof. For further discussion of these and other risks, see Chi-Med’s filings with the U.S. Securities and Exchange Commission and on AIM. Chi-Med undertakes no obligation to update or revise the information contained in this press release, whether as a result of new information, future events or circumstances or otherwise.
Contacts
| Investor Enquiries | ||
| Christian Hogg, CEO | +852 2121 8200 | |
| International Media Enquiries | ||
| Anthony Carlisle, Citigate Dewe Rogerson | +44 7973 611 888 (Mobile) | anthony.carlisle@cdrconsultancy.co.uk |
| U.S. Based Media Enquiries | ||
| Brad Miles, BMC Communications | +1 (917) 570 7340 (Mobile) | bmiles@bmccommunications.com |
| Susan Duffy, BMC Communications | +1 (917) 499 8887 (Mobile) | sduffy@bmccommunications.com |
| Investor Relations | ||
| Matt Beck, The Trout Group | +1 (917) 415 1750 (Mobile) | mbeck@troutgroup.com |
| David Dible, Citigate Dewe Rogerson | +44 7967 566 919 (Mobile) | david.dible@citigatedr.co.uk |
| Panmure Gordon (UK) Limited | ||
| Richard Gray / Andrew Potts | +44 (20) 7886 2500 |
London: Tuesday, January 10, 2017: Hutchison China MediTech Limited (“Chi-Med”) (AIM/Nasdaq: HCM) today announces that it has initiated a Phase I trial of its novel spleen tyrosine kinase (“Syk”) inhibitor, HMPL-523, in patients with hematological malignancies in China. The first patient was dosed on December 27, 2016. This study complements the ongoing Phase I trial in patients in Australia with hematological malignancies, which is expected to complete dose-escalation in the first half of 2017.
Syk, a non-receptor type of tyrosine kinase, plays a pivotal role in the regulation of the B-cell receptor (BCR) signaling pathway, which regulates proliferation, differentiation and survival of B lymphocytes. The abnormal activation of BCR signaling is closely related to transformation and development of B-cell lymphoma. Data from a recent pre-clinical study investigating the in vitro and in vivo anti-tumor activities of HMPL-523 was presented at the annual meeting of the American Society of Hematology held in San Diego, CA on December 5, 2016. The presentation is available at www.chi-med.com/wp-content/uploads/2016/12/pre161206_523ash.pdf.
Additional details about this study may be found at clinicaltrials.gov, using identifier NCT02857998.
Clinical development in immunology
HMPL-523 is also being studied in immunological indications. Clinical data for HMPL-523 in a Phase I dose-escalating study in healthy volunteers in Australia was recently presented at the 2016 annual meeting of the American College of Rheumatology/Association of Rheumatology Health Professionals, which was held in November 2016. The detailed poster presentation can be viewed at www.chi-med.com/wp-content/uploads/2016/11/pre1611141.png. The Company plans to initiate proof-of-concept clinical trials in the United States in 2017.
About B-cell signaling
The BCR signaling pathway regulates proliferation, differentiation and survival of B lymphocytes, a major cellular component of the immune system. The abnormal activation of BCR signaling is closely related to transformation and development of hematological cancers (i.e. B-cell malignancies), including lymphoma and leukemia, as well as autoimmune diseases, such as rheumatoid arthritis. Targeted BCR signaling therapies, including monoclonal antibodies and small molecules, have been proven to be clinically effective for the treatment of B-cell malignancies, leading to scientific and commercial success.
Syk is a key protein involved in the BCR signaling pathway.
About Chi-Med
Chi-Med is an innovative biopharmaceutical company which researches, develops, manufactures and sells pharmaceuticals and healthcare products. Its Innovation Platform, Hutchison MediPharma Limited, focuses on discovering and developing innovative therapeutics in oncology and autoimmune diseases for the global market. Its Commercial Platform manufactures, markets, and distributes prescription drugs and consumer health products in China.
Chi-Med is majority owned by the multinational conglomerate CK Hutchison Holdings Limited (SEHK: 0001). For more information, please visit: www.chi-med.com.
Forward-Looking Statements
This press release contains forward-looking statements within the meaning of the “safe harbor” provisions of the U.S. Private Securities Litigation Reform Act of 1995. These forward-looking statements reflect Chi-Med’s current expectations regarding future events, including its expectations for the clinical development of HMPL-523, plans to initiate clinical studies for HMPL-523 (including proof-of-concept trials in the United States), its expectations as to whether such studies would meet their primary or secondary endpoints, and its expectations as to the timing of the completion and the release of results from such studies. Forward-looking statements involve risks and uncertainties. Such risks and uncertainties include, among other things, assumptions regarding enrollment rates, timing and availability of subjects meeting a study’s inclusion and exclusion criteria, changes to clinical protocols or regulatory requirements, unexpected adverse events or safety issues, the ability of drug candidate HMPL-523 to meet the primary or secondary endpoint of a study, to obtain regulatory approval in different jurisdictions, to gain commercial acceptance after obtaining regulatory approval, the potential market of HMPL-523 for a targeted indication and the sufficiency of funding. Existing and prospective investors are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date hereof. For further discussion of these and other risks, see Chi-Med’s filings with the U.S. Securities and Exchange Commission and on AIM. Chi-Med undertakes no obligation to update or revise the information contained in this press release, whether as a result of new information, future events or circumstances or otherwise.
Contacts
| Investor Enquiries | ||
| Christian Hogg, CEO | +852 2121 8200 | |
| International Media Enquiries | ||
| Anthony Carlisle, Citigate Dewe Rogerson | +44 7973 611 888 (Mobile) | anthony.carlisle@cdrconsultancy.co.uk |
| U.S. Based Media Enquiries | ||
| Brad Miles, BMC Communications | +1 (917) 570 7340 (Mobile) | bmiles@bmccommunications.com |
| Susan Duffy, BMC Communications | +1 (917) 499 8887 (Mobile) | sduffy@bmccommunications.com |
| Investor Relations | ||
| Matt Beck, The Trout Group | +1 (917) 415 1750 (Mobile) | mbeck@troutgroup.com |
| David Dible, Citigate Dewe Rogerson | +44 7967 566 919 (Mobile) | david.dible@citigatedr.co.uk |
| Panmure Gordon (UK) Limited | ||
| Richard Gray / Andrew Potts | +44 (20) 7886 2500 |
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