London: Wednesday, September 30, 2020: Hutchison China MediTech Limited (“Chi-Med”) (AIM/Nasdaq: HCM) hereby notifies the market that as at September 30, 2020, the issued share capital of Chi-Med consisted of 710,785,545 ordinary shares of US$0.10 each, with each share carrying one right to vote and with no shares held in treasury.
The above figure of 710,785,545 may be used by shareholders as the denominator for the calculations by which they could determine if they are required to notify their interest in, or a change to their interest in, Chi-Med under the Financial Conduct Authority’s Disclosure Rules and Transparency Rules.
For illustrative purposes only, the 710,785,545 ordinary shares would be equivalent to 710,785,545 CREST depositary interests (each equating to one ordinary share) which are traded on AIM or, if the CREST depositary interests were converted in their entirety, equivalent to 142,157,109 American depositary shares (each equating to five ordinary shares) which are traded on Nasdaq.
About Chi-Med
Chi-Med (Nasdaq/AIM: HCM) is an innovative, commercial-stage, biopharmaceutical company committed, over the past twenty years, to the discovery and global development of targeted therapies and immunotherapies for the treatment of cancer and immunological diseases. It has a portfolio of nine cancer drug candidates currently in clinical studies around the world and extensive commercial infrastructure in its home market of China. For more information, please visit: www.chi-med.com.
Investor Enquiries |
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Mark Lee, Senior Vice President | +852 2121 8200 |
Annie Cheng, Vice President | +1 (973) 567 3786 |
Media Enquiries |
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Americas | |
Brad Miles, Solebury Trout | +1 (917) 570 7340 (Mobile) bmiles@troutgroup.com |
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Ben Atwell / Alex Shaw, FTI Consulting | +44 20 3727 1030 / +44 7771 913 902 (Mobile) / +44 7779 545 055 (Mobile) Chi-Med@fticonsulting.com |
Asia | |
Joseph Chi Lo, Brunswick | +852 9850 5033 (Mobile) jlo@brunswickgroup.com |
Zhou Yi, Brunswick | +852 9783 6894 (Mobile) yzhou@brunswickgroup.com |
Nominated Advisor |
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Freddy Crossley / Atholl Tweedie, Panmure Gordon (UK) Limited |
+44 (20) 7886 2500 |
Jianming Xu*, Lin Shen*, Chunmei Bai*, Wei Wang*, Jie Li, Xianjun Yu, Zhiping Li, Enxiao Li, Xianglin Yuan, Yihebali Chi, Yongmei Yin, Wenhui Lou, Nong Xu, Yuxian Bai, Tao Zhang, Dianrong Xiu, Xiuwen Wang, Ying Yuan, Jia Chen, Shukui Qin, Ru Jia, Ming Lu, Yuejuan Cheng, Zhiwei Zhou, Jing Li, James He, Weiguo Su
Background
Surufatinib showed superior efficacy in extrapancreatic neuroendocrine tumours (NETs) in the phase 3 SANET-ep study. In SANET-p, we aimed to assess the efficacy and safety of surufatinib in patients with advanced pancreatic NETs.
Methods
SANET-p was a multicentre, randomised, double-blind, placebo-controlled, phase 3 study, done in 21 hospitals across China. Eligible patients were adults (aged 18 years or older) with progressive, advanced, well differentiated pancreatic NETs, Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, and progression on up to two kinds of previous systemic regimens for advanced disease. Patients were randomly assigned (2:1) via an interactive web response system to receive 300 mg of surufatinib or placebo, taken orally once per day in consecutive 4-week treatment cycles until disease progression, intolerable toxicity, withdrawal of consent, poor compliance, use of other antitumour medication, pregnancy, loss to follow-up, or if the investigator deemed discontinuation in the patient’s best interest. Randomisation was done centrally using stratified block randomisation (block size three), stratified by pathological grade, previous systemic antitumour treatment, and ECOG performance status score. Patients, investigators, research staff, and the sponsor study team were masked to treatment allocation. Crossover to surufatinib was permitted for patients in the placebo group with disease progression. The primary endpoint was investigator-assessed progression-free survival in the intention-to-treat population, which included all patients in randomisation. A pre-planned interim analysis was done at 70% of the predicted progression-free survival events. This study is registered at ClinicalTrials.gov, NCT02589821.
Findings
Between Feb 18, 2016, and Nov 11, 2019, of 264 patients who were screened, 172 (65%) patients were randomly assigned to receive surufatinib (n=113) or placebo (n=59). The median follow-up was 19·3 months (95% CI 9·3–19·4) in the surufatinib group and 11·1 months (5·7–35·9) in the placebo group. The median investigator-assessed progression-free survival was 10·9 months (7·5–13·8) for surufatinib versus 3·7 months (2·8–5·6) for placebo (hazard ratio 0·49, 95% CI 0·32–0·76; p=0·0011). The trial met the early stopping criteria at the interim analysis and was terminated on recommendation from the independent data monitoring committee. The most common grade 3 or worse treatment-related adverse events were hypertension (43 [38%] of 113 with surufatinib vs four [7%] of 59 with placebo), proteinuria (11 [10%] vs one [2%]), and hypertriglyceridaemia (eight [7%] vs none). Treatment-related serious adverse events were reported in 25 (22%) patients in the surufatinib group and four (7%) patients in the placebo group. There were three on-treatment deaths in the surufatinib group, including two deaths due to adverse events (gastrointestinal haemorrhage [possibly treatment-related] and cerebral haemorrhage [unlikely to be treatment-related]), and one death attributed to disease progression. One on-treatment death in the placebo group was attributed to disease progression.
Interpretation
Surufatinib significantly improves progression-free survival and has an acceptable safety profile in patients with progressive, advanced pancreatic NETs, and could be a potential treatment option in this patient population.
Funding: Hutchison MediPharma.
Trial Registration: ClinicalTrials.gov Identifier: NCT02589821.
Please follow the link below to access the publication:
Lancet Oncol. 2020; S1470-2045(20)30493-9. [published online ahead of print, 2020 Sep 20]
DOI: 10.1016/S1470-2045(20)30493-9
Jianming Xu*, Lin Shen*, Zhiwei Zhou, Jie Li, Chunmei Bai, Yihebali Chi, Zhiping Li, Nong Xu, Enxiao Li, Tianshu Liu, Yuxian Bai, Ying Yuan, Xingya Li, Xiuwen Wang, Jia Chen, Jieer Ying, Xianjun Yu, Shukui Qin, Xianglin Yuan, Tao Zhang, Yanhong Deng, Dianrong Xiu, Ying Cheng, Min Tao, Ru Jia, Wei Wang, Jing Li, Songhua Fan, Mengye Peng, Weiguo Su
Background
Therapeutic options for advanced neuroendocrine tumours (NETs) are limited. We investigated the efficacy and safety of surufatinib (HMPL-012, sulfatinib) in patients with extrapancreatic NETs.
Methods
SANET-ep was a randomised, double-blind, placebo-controlled, phase 3 trial undertaken at 24 hospitals across China. Patients (aged 18 years or older) with unresectable or metastatic, well differentiated, extrapancreatic NETs, with an Eastern Cooperative Oncology Group performance status of 0 or 1, and progression on no more than two types of previous systemic regimens were enrolled. Patients were centrally randomly assigned (2:1) using stratified block randomisation (block size 3) via an interactive web response system to receive oral surufatinib at 300 mg per day or matching placebo. Randomisation was stratified by tumour origin, pathological grade, and previous treatment. Patients, investigators, research staff and the sponsor study team were masked to treatment allocation. Crossover to the surufatinib group was allowed for patients in the placebo group at disease progression. The primary endpoint was investigator-assessed progression-free survival, which was analysed in the intention-to-treat population. A preplanned interim analysis was done at 70% of predicted progression-free survival events. This study was registered with ClinicalTrials.gov, NCT02588170. Follow-up is ongoing.
Findings
Between Dec 9, 2015, and March 31, 2019, 198 patients were randomly assigned to surufatinib (n=129) or placebo (n=69). Median follow-up was 13·8 months (95% CI 11·1–16·7) in the surufatinib group and 16·6 months (9·2–not calculable) in the placebo group. Investigator-assessed median progression-free survival was 9·2 months (95% CI 7·4–11·1) in the surufatinib group versus 3·8 months (3·7–5·7) in the placebo group (hazard ratio 0·33; 95% CI 0·22–0·50; p<0·0001). As the trial met the predefined criteria for early discontinuation of the study at the interim analysis, the study was terminated early, as recommended by the independent data monitoring committee. The most common treatment-related adverse events of grade 3 or worse were hypertension (47 [36%] of 129 patients in the surufatinib group vs nine [13%] of 68 patients in the placebo group) and proteinuria (25 [19%] vs zero). Treatment-related serious adverse events were reported in 32 (25%) of 129 patients in the surufatinib group and nine (13%) of 68 patients in the placebo group. Treatment-related deaths occurred in three patients in the surufatinib group (disseminated intravascular coagulation and hepatic encephalopathy, liver injury, and death with unknown reason) and one patient in the placebo group (cachexia and respiratory failure).
Interpretation
Progression-free survival was significantly longer in patients given surufatinib compared with patients given placebo, and surufatinib has a favourable benefit-to-risk profile in patients with progressive, advanced, well differentiated extrapancreatic NETs. Our results suggest that surufatinib might be a new treatment option for this population.
Funding: Hutchison MediPharma.
Trial Registration: ClinicalTrials.gov Identifier: NCT02588170.
Please follow the link below to access the publication:
Lancet Oncol. 2020;S1470-2045(20)30496-4. [published online ahead of print, 2020 Sep 20]
DOI: 10.1016/S1470-2045(20)30496-4
Title: | Surufatinib (S) for patients (Pts) with advanced pancreatic neuroendocrine tumors (SANET-p): a randomized, double-blind, placebo (P)-controlled Phase III trial (NCT02589821) |
Lead Author: | Jianming Xu, Head of the Department of Gastrointestinal Oncology, The Fifth Medical Center, General Hospital of the PLA |
Session: | Proffered Paper – NETs |
Abstract Number: | 1156O |
Date & Time: | Sunday, September 20, 2020 2:25 PM CEST |
Room: | Channel 3 |
Surufatinib, a kinase inhibitor targeting vascular endothelial growth factor receptors, fibroblast growth factor receptor 1 and colony stimulating factor-1 receptor, has demonstrated superior efficacy in extra-pancreatic neuroendocrine tumors (NETs) in a prior phase III study (ESMO 2019 Abs. LBA76). Here we report results from a parallel study of surufatinib in pancreatic NETs (pNETs).
The study evaluated the efficacy and safety of S in Pts with well-differentiated (pathological grade 1 or 2), progressive, unresectable or metastatic pNETs. Pts were randomized in a 2:1 ratio to receive S or P, 300 mg, orally, once daily, until disease progression or intolerable adverse events. Crossover at disease progression was allowed. The primary endpoint was investigator-assessed progression-free survival (PFS).
By the cutoff date on 11 November 2019 for the pre-planned interim analysis, 172 Pts were randomized, 113 pts to S and 59 to P. Baseline characteristics were well balanced. The study met the primary endpoint; investigator-assessed median PFS was 10.9 vs. 3.7 months in S and P arms, respectively, with hazard ratio (HR)=0.491; 95% confidence interval [CI]: 0.319–0.755; p=0.0011. Analysis by a blinded independent radiology committee confirmed PFS improvement (13.9 vs. 4.6 months; HR=0.339; 95% CI: 0.209–0.549; p<0.0001). The investigator-assessed objective response rate was 19.2% with S and 1.9% with P (p=0.0021). Most common (≥5% in either arm) grade ≥3 treatment-emergent adverse events (TEAEs) were hypertension (38.9% in S arm vs. 8.5% in P arm), proteinuria (9.7% vs. 1.7%), hypertriglyceridaemia (7.1% vs. 0), alanine aminotransferase increased and gamma-glutamyltransferase increased (both 2.7% vs. 5.1%). TEAEs leading to drug discontinuation occurred in 10.6% pts vs. 6.8% pts in S and P arm respectively.
Surufatinib significantly improved the PFS in Pts with progressive, well-differentiated advanced pNETs. The safety profile was manageable and consistent with observations in prior studies. Surufatinib represents a promising treatment option in the armamentarium against pNETs.
Clinical trial identification: NCT02589821.
Legal entity responsible for the study: Hutchison MediPharma Limited.
Funding: Hutchison MediPharma Limited.
J. Li, S. Fan: Full/Part-time employment: Hutchison MediPharma Limited. W. Su: Shareholder/Stockholder/Stock options, Full/Part-time employment: Hutchison MediPharma Limited. All other authors have declared no conflicts of interest.
― Phase III SANET-p demonstrated surufatinib reduces the risk of disease progression or death by 51% in patients with pancreatic neuroendocrine tumors (“NET”) ―
― SANET-p results complement previously presented positive Phase III SANET-ep results in patients with non-pancreatic NET, including across multiple subgroups ―
― Results of both SANET-p and SANET-ep studies published in The Lancet Oncology –
Hong Kong, Shanghai, & Florham Park, NJ: Sunday, September 20, 2020: Hutchison China MediTech Limited (“Chi-Med”) (Nasdaq/AIM: HCM) today announces that positive results of the Phase III study of surufatinib in advanced neuroendocrine tumors – pancreatic (“SANET-p”) were presented as a proffered paper session at the European Society for Medical Oncology (“ESMO”) Virtual Congress 2020 (Abstract Number 1156O). Results from SANET-p, in addition to previously presented results from Phase III study of surufatinib in advanced neuroendocrine tumors – extra-pancreatic (“SANET-ep”), are published today in The Lancet Oncology.
“Surufatinib demonstrated statistically significant and clinically meaningful benefits in patients with advanced pancreatic NET. These results, combined with positive results from the parallel study of surufatinib in patients with non-pancreatic NET, support surufatinib as a promising treatment option for well-differentiated NET patients regardless of tumor origin,” commented Dr. Jianming Xu, lead investigator for the SANET-p study, Head of the Department of Gastrointestinal Oncology, The Fifth Medical Center, General Hospital of the PLA in Beijing.
As announced in January 2020, the Independent Data Monitoring Committee (“IDMC”) for the SANET-p trial recommended that the study stop early because it had met the pre-defined primary endpoint of progression free survival (“PFS”) during a planned interim analysis. At data cut-off as of November 11, 2019, 172 patients were randomized 2:1 to treatment with either 300 mg of surufatinib orally daily (N=113) or placebo control (N=59), on a 28-day cycle. Median PFS was 10.9 months for patients treated with surufatinib, as compared to 3.7 months for patients in the placebo group (hazard ratio [“HR”] 0.491; 95% confidence interval [“CI”] 0.391-0.755; p=0.0011). Benefit was observed across most major subgroups of pNET patients. Objective response rates (ORR) were 19.2%[1] for the 104 efficacy evaluable patients in the surufatinib group versus 1.9%[2] for the 53 efficacy evaluable patients in the placebo group, with a disease control rate (DCR) of 80.8% versus 66.0%, respectively. Most patients in the trial had Grade 2 disease with heavy tumor burden, including liver metastasis and multiple organ involvement. Efficacy was also supported by Blinded Independent Image Review Committee (BIIRC) assessment, with a median PFS of 13.9 months for surufatinib as compared to 4.6 months for placebo (HR 0.339; 95% CI 0.209-0.549; p<0.0001).
The safety profile of surufatinib was manageable and consistent with observations in prior studies. Treatment was well tolerated for most patients, with discontinuation rates as a result of treatment emergent adverse events of 10.6% in the surufatinib group as compared to 6.8% in the placebo group.
In the U.S., the Food and Drug Administration (“FDA”) granted surufatinib two Fast Track Designations, for both the non-pancreatic NET and pancreatic NET development programs, and Orphan Drug Designation for pancreatic NET development. A rolling new drug application (“NDA”) submission is being prepared, to be followed by a marketing authorization application (“MAA”) submission to the European Medicines Agency (“EMA”) in Europe, based on the robust data from the two studies and the ongoing multi-cohort Phase Ib study in the U.S. In December 2019, an NDA for surufatinib for the treatment of patients with advanced non-pancreatic NET was granted Priority Review status by the China National Medical Products Administration (“NMPA”). A second NDA for surufatinib for the treatment of patients with advanced pancreatic NET has also been accepted by the NMPA.
NET form in cells that interact with the nervous system or in glands that produce hormones. They can originate in various parts of the body, most often in the gut or the lungs and can be benign or malignant. NET are typically classified as pancreatic NET or non-pancreatic NET. Approved targeted therapies include Sutent® and Afinitor® for pancreatic NET, or well-differentiated, non-functional gastrointestinal or lung NET.
According to Frost and Sullivan, there were 19,000 newly diagnosed cases of NET in the U.S. in 2018. Importantly, NET are associated with a relatively long duration of survival compared to other tumors. As a result, there were approximately 141,000 estimated patients living with NET in the U.S. in 2018.
In China, there were approximately 67,600 newly diagnosed NET patients in 2018 and, considering the current incidence to prevalence ratio in China, potentially as many as 300,000 patients living with the disease in the country.[3]
Surufatinib is a novel, oral angio-immuno kinase inhibitor that selectively inhibits the tyrosine kinase activity associated with vascular endothelial growth factor receptor (VEGFR) and fibroblast growth factor receptor (FGFR), which both inhibit angiogenesis, and colony stimulating factor-1 receptor (CSF-1R), which regulates tumor-associated macrophages, promoting the body’s immune response against tumor cells. Its unique dual mechanism of action may be very suitable for possible combinations with other immunotherapies, where there may be synergistic anti-tumor effects.
Chi-Med currently retains all rights to surufatinib worldwide.
NET in the U.S. and Europe: In the U.S., surufatinib was granted Fast Track Designations for development in pancreatic and non-pancreatic (extra-pancreatic) NET in April 2020, and Orphan Drug Designation for pancreatic NET in November 2019. A U.S. FDA NDA submission is being prepared, to be followed by a MAA submission to the EMA in Europe. The basis to support these filings includes the completed SANET-ep and SANET-p studies, along with existing data from surufatinib in U.S. non-pancreatic and pancreatic NET patients (clinicaltrials.gov identifier: NCT02549937).
Non-pancreatic NET in China: In November 2019, a NDA for surufatinib for the treatment of patients with advanced non-pancreatic NET was accepted for review by the NMPA and granted Priority Review status in December 2019. The NDA is supported by data from the successful SANET-ep study, a Phase III study of surufatinib in patients with advanced non-pancreatic NET in China for whom there is no effective therapy. A 198-patient interim analysis was conducted in June 2019, leading the IDMC to determine that the study met the pre-defined primary endpoint of PFS and should be stopped early. The positive results of this trial were highlighted in an oral presentation at the 2019 ESMO Congress (clinicaltrials.gov identifier: NCT02588170) and published in The Lancet Oncology in September 2020.[4] Median PFS was 9.2 months for patients treated with surufatinib, as compared to 3.8 months for patients in the placebo group (HR 0.334; 95% CI: 0.223-0.499; p<0.0001).
Pancreatic NET in China: In 2016, we initiated the SANET-p study, which is a pivotal Phase III study in patients with low- or intermediate-grade, advanced pancreatic NET in China. Following an interim analysis review conducted in January 2020 by the IDMC that recommended the registrational study be terminated early as the pre-defined primary endpoint of PFS had already been met (clinicaltrials.gov identifier: NCT02589821), leading to a second NDA accepted by the China NMPA. The results of this study were presented at the ESMO Virtual Congress 2020 and published simultaneously in The Lancet Oncology.[5]
Biliary tract cancer in China: In March 2019, we initiated a Phase IIb/III study comparing surufatinib with capecitabine in patients with advanced biliary tract cancer whose disease progressed on first-line chemotherapy. The primary endpoint is overall survival (OS) (clinicaltrials.gov identifier NCT03873532).
Immunotherapy combinations: We have entered into collaboration agreements to evaluate the safety, tolerability and efficacy of surufatinib in combination with anti-PD-1 monoclonal antibodies, including with tislelizumab (BGB-A317, developed by BeiGene, Ltd.), Tuoyi® (toripalimab, developed by Shanghai Junshi Biosciences Co. Ltd.) and Tyvyt® (sintilimab, developed by Innovent Biologics, Inc.), which are approved in China.
Chi-Med (Nasdaq/AIM: HCM) is an innovative, commercial-stage, biopharmaceutical company committed, over the past twenty years, to the discovery and global development of targeted therapies and immunotherapies for the treatment of cancer and immunological diseases. It has a portfolio of nine cancer drug candidates currently in clinical studies around the world and extensive commercial infrastructure in its home market of China. For more information, please visit: www.chi-med.com.
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 regarding the submission of an NDA for surufatinib for the treatment of NET in the U.S., China and other jurisdictions, the therapeutic potential of surufatinib for the treatment of patients with NET, the further clinical development for surufatinib in this and other indications, 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 the sufficiency of the clinical data to support NDA approval of surufatinib for the treatment of patients with NET in the U.S. and China or other jurisdictions, its potential to gain expeditious approvals from regulatory authorities, the safety profile of surufatinib, 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 surufatinib, including as a combination therapy, to meet the primary or secondary endpoint of a study, its ability to fund, implement and complete its further clinical development and commercialization plans for surufatinib, the timing of these events, and the impact of the COVID-19 pandemic on general economic, regulatory and political conditions.. In addition, as certain studies rely on the use of capecitabine, tislelizumab, Tuoyi®, and Tyvyt® as combination therapeutics with surufatinib, such risks and uncertainties include assumptions regarding the safety, efficacy, supply and continued regulatory approval of these therapeutics. 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.
Investor Enquiries |
|
Mark Lee, Senior Vice President | +852 2121 8200 |
Annie Cheng, Vice President | +1 (973) 567 3786 |
Media Enquiries |
|
Americas | |
Brad Miles, Solebury Trout | +1 (917) 570 7340 (Mobile) bmiles@troutgroup.com |
Europe | |
Ben Atwell / Alex Shaw, FTI Consulting | +44 20 3727 1030 / +44 7771 913 902 (Mobile) / +44 7779 545 055 (Mobile) Chi-Med@fticonsulting.com |
Asia | |
Joseph Chi Lo, Brunswick | +852 9850 5033 (Mobile) jlo@brunswickgroup.com |
Zhou Yi, Brunswick | +852 9783 6894 (Mobile) yzhou@brunswickgroup.com |
Nominated Advisor |
|
Freddy Crossley / Atholl Tweedie, Panmure Gordon (UK) Limited |
+44 (20) 7886 2500 |
Title: | Phase (Ph) 1/1b Trial of Fruquintinib (Fru) in Patients (Pts) with Advanced Solid Tumors: Preliminary Results of the Dose Expansion (Exp) Cohort in Refractory Metastatic Colorectal Cancer (mCRC) |
Lead Author: | N. Arvind Dasari, Associate Professor, Department of Gastrointestinal (GI) Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center |
Session: | e-Poster Display Session |
Abstract Number: | 458P |
Date available: | Thursday, September 17, 2020 |
Fru is a highly selective, novel vascular endothelial growth factor receptor (VEGFR) -1, -2, and -3 tyrosine kinase inhibitor (TKI). In the ph 3 FRESCO study (NCT02314819) that led to its approval in China, Fru 5mg daily, 3 weeks (wks) on 1 wk off, improved the median overall survival in pts with mCRC in third line and beyond when compared to placebo (9.3 v 6.6 months); hazard ratio 0.65 (P < 0.001).
This is an ongoing ph 1/1b open-label, dose escalation (esc)/exp study conducted in the US. The dose esc was previously reported with confirmation of the approved dose/schedule in China. Here we present the preliminary safety and efficacy data from pts with refractory mCRC (exp) who progressed on all standard therapies including TAS-102 and/or regorafenib (rego).
To date, 24 pts have been treated; age <65 years (62.5%), Caucasian (75%), female (54.2%), and ECOG PS 1 (62.5%). Median number of prior therapies was 4 (range: 1-7), and 7 pts (29.2%) received rego, 11 (45.8%) received TAS-102 and 6 (25.0%) received both rego and TAS-102. 16 pts remain on treatment. The median duration of Fru treatment was 2.8 months (range: 0.7– 10.4). The most frequently reported treatment-related (TR) treatment emergent adverse events (TEAEs) of any grade (Gr)(≥20% of pts) were hypertension (37.5%), proteinuria (29.2%), fatigue (29.2%), hand-foot syndrome (HFS)(29.2%), diarrhea (25.0%), headache (20.8%), stomatitis (20.8%), and elevated alk phos (20.8%). 8 (33.3%) pts reported Gr ≥3 TR TEAEs. Those that occurred in ≥5% of pts were hypertension (25%), proteinuria (8.3%) and fatigue (8.3%). No Gr ≥3 HFS was seen. Preliminary efficacy in pts who had a post-baseline scan and at least 3 months of follow up or discontinued treatment early (n=14) showed stable disease in 11 pts, with a disease control rate of 78.6%.
Fru is generally well-tolerated in heavily pretreated pts with refractory mCRC, with less HFS compared to other VEGFR TKIs. Evidence of anticancer activity was also observed in these pts. The multi-cohort dose exp is ongoing. Fru is being further investigated in refractory mCRC in a global Ph 3 study (NCT04322539).
Clinical trial identification: NCT03251378 (first posted 16 Aug 2017).
Editorial acknowledgement: Sarah Milner, PhD (Synchrogenix) provided editorial assistance.
Legal entity responsible for the study: Hutchison MediPharma Limited.
Funding: Hutchison MediPharma Limited.
N.A. Dasari: Advisory/Consultancy, Research grant/Funding (institution): Hutchison MediPharma Ltd. A. Wang-Gillam: Honoraria (self), Advisory/Consultancy: Bayer; Honoraria (self), Advisory/Consultancy: AstraZeneca; Honoraria (self), Advisory/Consultancy: Esai; Honoraria (self), Advisory/Consultancy: Merck; Honoraria (self), Advisory/Consultancy: Bristol Myer Squibb; Honoraria (self), Advisory/Consultancy: Tyme; Honoraria (self), Advisory/Consultancy: Merrimack; Honoraria (self), Advisory/Consultancy: Jacobio; Research grant/Funding (institution): Barns Jewish Foundation; Research grant/Funding (institution): Pancreatic Cancer Action Network. J.M. Hubbard: Research grant/Funding (institution): Merck; Research grant/Funding (institution): Boston Biomedical; Research grant/Funding (institution): Treos Bio; Research grant/Funding (institution): Taiho; Research grant/Funding (institution): Senhwa Pharmaceuticals; Research grant/Funding (institution): Bayer; Research grant/Funding (institution): Incyte; Research grant/Funding (institution): TriOncology; Research grant/Funding (institution): Seattle Genetics; Research grant/Funding (institution): Hutchison MediPharma. A. Fernandez: Full/Part-time employment: Hutchison MediPharma International, Inc; Shareholder/Stockholder/Stock options: Hutchison China Meditech Ltd. S. Nanda: Full/Part-time employment: Hutchison MediPharma International, Inc; Shareholder/Stockholder/Stock options: Hutchison China Meditech Ltd. M. Kania: Full/Part-time employment: Hutchison MediPharma International, Inc; Shareholder/Stockholder/Stock options: Hutchison China Meditech Ltd. W.R. Schelman: Full/Part-time employment: Hutchison MediPharma International, Inc; Shareholder/Stockholder/Stock options: Hutchison China Meditech Ltd. T.S. Bekaii-Saab: Research grant/Funding (institution): Boston Biomedical; Advisory/Consultancy, Research grant/Funding (institution): Bayer; Research grant/Funding (institution): Amgen; Advisory/Consultancy, Research grant/Funding (institution): Merck; Research grant/Funding (institution): Celgene; Advisory/Consultancy, Research grant/Funding (institution), IDMC/DSMB: Eli Lilly; Advisory/Consultancy, Research grant/Funding (institution): Ipsen; Research grant/Funding (institution): Clovis; Advisory/Consultancy, Research grant/Funding (institution): Seattle Genetics; Advisory/Consultancy, Research grant/Funding (institution): Array Biopharma; Advisory/Consultancy, Research grant/Funding (institution): Genentech; Research grant/Funding (institution): Abgenomics; Advisory/Consultancy, Research grant/Funding (institution): Incyte; Research grant/Funding (institution): Bristol Myers Squibb; Advisory/Consultancy: Boehringer Ingelheim; Advisory/Consultancy: Treosbio; Advisory/Consultancy: Sobi; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy, IDMC/DSMB: Exelixis; Advisory/Consultancy, IDMC/DSMB: PanCan; Advisory/Consultancy, IDMC/DSMB: 1Globe; Advisory/Consultancy: Imugene; Advisory/Consultancy: Immuneering; Advisory/Consultancy: Sun Biopharma.
Title: | Subgroup analysis by Ki-67 and primary tumor origins of the randomized, placebo-controlled phase 3 study of surufatinib in advanced well-differentiated extrapancreatic neuroendocrine tumors (SANET-ep) |
Lead Author: | Zhiwei Zhou, Director, Department of Gastric and Pancreatic Surgery, Sun Yat-sen University Cancer Center |
Session: | e-Poster Display Session |
Abstract Number: | 1165P |
Date available: | Thursday, September 17, 2020 |
Surufatinib, a tyrosine kinase inhibitor targeting vascular endothelial growth factor receptors (1,2,3), fibroblast growth factor receptor 1 and colony stimulating factor 1 receptor, has demonstrated superior efficacy in extrapancreatic neuroendocrine tumors (NETs) in a phase III study (SANET-ep, ESMO 2019 Abs. LBA76). The proliferation marker Ki-67 and primary tumor origins are the major prognostic factors in NETs.
The post-hoc efficacy analysis of surufatinib versus placebo was conducted by Ki-67 subcategory (<3%, 3-10%, >10%) and primary tumor origins (foregut, midgut, hindgut, others or unknown) in patients (pts) with advanced well-differentiated (grade 1 or 2) extrapancreatic NETs. The primary endpoint (progression-free survival [PFS]) and secondary endpoint (objective response rate [ORR]) both by investigator assessment (RECIST1.1) were analyzed.
Median PFS was significantly prolonged with surufatinib compared to placebo in subgroups of Ki-67 3-10% (7.6 vs 4.6 months [mo], hazard ratio [HR] 0.47, P=0.0012), Ki-67 >10% (8.3 vs 2.1 mo, HR 0.14, P<0.0001), foregut (8.4 vs 4.6 mo, HR 0.29, P=0.0001) and hindgut (8.3 vs 2.1 mo, HR 0.35, P=0.0014). There was numerical PFS improvement with surufatinib compared to placebo in the rest subgroups: Ki 67 <3% (13.9 vs 7.4 mo, HR 0.43, P=0.0557), midgut (19.2 vs 8.9 mo, HR not analyzed due to small sample size) and unknown origin (9.2 vs 5.5 mo, HR 0.56, P=0.2943). ORR in the subgroups of Ki-67 <3%, 3-10%, >10% with surufatinib were 4.8%, 7.7%% and 20.0% respectively. There was no objective response in the placebo arm. ORR in the subgroups of foregut, midgut and unknown origin with surufatinib was 18.4%, 16.7% and 10.0% respectively while no response was observed in subgroups of hindgut or other origins.
Surufatinib demonstrated clinically significant benefits for pts with advanced well-differentiated extrapancreatic NETs compared to placebo. Results of this exploratory analysis were consistent with those reported for the SANET-ep primary analysis, and improved outcomes were observed across major subgroups.
Clinical trial identification: NCT02588170.
Legal entity responsible for the study: Hutchison MediPharma Limited.
Funding: Hutchison MediPharma Limited.
J. Li, J. He: Full/Part-time employment: Hutchison MediPharma Limited. W. Su: Shareholder/Stockholder/Stock options, Full/Part-time employment: Hutchison MediPharma Limited. All other authors have declared no conflicts of interest.
Hong Kong, Shanghai, & Florham Park, NJ: Thursday, September 17, 2020: Hutchison China MediTech Limited (“Chi-Med”) (Nasdaq/AIM: HCM) today announces that its New Drug Application (“NDA”) for surufatinib for the treatment of patients with advanced pancreatic neuroendocrine tumors (“NET”) has been accepted for review by the China National Medical Products Administration (“NMPA”).
The NDA is supported by data from the successful SANET-p study, a Phase III pivotal study of surufatinib in advanced neuroendocrine tumors – pancreatic patients in China for whom there is no effective therapy. The study was terminated early following positive interim analysis completed in January 2020. The positive results of the study demonstrating improvement in progression free survival (“PFS”) will be presented at the 2020 European Society for Medical Oncology Congress (“ESMO”) (Abstract Number 1156O). This is the second NDA acceptance for surufatinib. The first NDA for non-pancreatic NET was accepted by the NMPA in November 2019 and was granted priority review status in December 2019.
Chi-Med currently retains all worldwide rights to surufatinib. This drug candidate is under investigation in multiple solid tumors in China and the U.S., both as a monotherapy and in combination with immunotherapies.
In the U.S., the Food and Drug Administration (“FDA”) granted Fast Track Designation status to surufatinib for both the non-pancreatic NET and pancreatic NET development programs in April 2020. Chi-Med has initiated preparatory work for the U.S. NDA and intends to utilize a rolling submission, which is expected to start in late 2020. In addition, the Marketing Authorization Application (“MAA”) submission in Europe is planned for 2021.
NETs form in cells that interact with the nervous system or in glands that produce hormones. They can originate in various parts of the body, most often in the gut or the lungs and can be benign or malignant. NET are typically classified as pancreatic NET or non-pancreatic NET. Approved targeted therapies include Sutent® and Afinitor® for pancreatic NET, or well-differentiated, non-functional gastrointestinal or lung NET.
According to Frost and Sullivan, there were 19,000 newly diagnosed cases of NET in the U.S. in 2018. Importantly, NETs are associated with a relatively long duration of survival compared to other tumors. As a result, there were approximately 141,000 estimated patients living with NET in the U.S. in 2018.
In China, there were approximately 67,600 newly diagnosed NET patients in 2018 and, considering the current incidence to prevalence ratio in China, potentially as many as 300,000 patients living with the disease in the country.
Surufatinib is a novel, oral angio-immuno kinase inhibitor that selectively inhibits the tyrosine kinase activity associated with vascular endothelial growth factor receptor (VEGFR) and fibroblast growth factor receptor (FGFR), which both inhibit angiogenesis, and colony stimulating factor-1 receptor (CSF-1R), which regulates tumor-associated macrophages, promoting the body’s immune response against tumor cells. Its unique dual mechanism of action may be very suitable for possible combinations with other immunotherapies, where there may be synergistic anti-tumor effects.
Chi-Med currently retains all rights to surufatinib worldwide.
NET in the U.S. and Europe: In the U.S., surufatinib was granted Fast Track Designations for development in pancreatic and non-pancreatic (extra-pancreatic) NET in April 2020, and Orphan Drug Designation for pancreatic NET in November 2019. A U.S. FDA NDA submission is being prepared, to be followed by a MAA submission to the EMA in Europe. The basis to support these filings includes the completed SANET-ep and SANET-p studies, along with existing data from surufatinib in U.S. non-pancreatic and pancreatic NET patients (clinicaltrials.gov identifier: NCT02549937).
Non-pancreatic NET in China: In November 2019, a NDA for surufatinib for the treatment of patients with advanced non-pancreatic NET was accepted for review by the NMPA and granted Priority Review status in December 2019. The NDA is supported by data from the successful SANET-ep study, a Phase III study of surufatinib in patients with advanced non-pancreatic NET in China for whom there is no effective therapy. A 198-patient interim analysis was conducted in June 2019, leading the Independent Data Monitoring Committee (“IDMC”) to determine that the study met the pre-defined primary endpoint of progression-free survival (“PFS”) and should be stopped early. The positive results of this trial were highlighted in an oral presentation at ESMO 2019 (clinicaltrials.gov identifier: NCT02588170).
Pancreatic NET in China: In 2016, we initiated the SANET-p study, which is a pivotal Phase III study in patients with low- or intermediate-grade, advanced pancreatic NET in China. Following an interim analysis review conducted in January 2020 by the IDMC that recommended the registrational study be terminated early as the pre-defined primary endpoint of PFS had already been met (clinicaltrials.gov identifier: NCT02589821), leading to a second NDA accepted by the China NMPA. The results of this study will be presented at ESMO 2020.
Biliary tract cancer in China: In March 2019, we initiated a Phase IIb/III study comparing surufatinib with capecitabine in patients with advanced biliary tract cancer whose disease progressed on first-line chemotherapy. The primary endpoint is overall survival (OS) (clinicaltrials.gov identifier NCT03873532).
Immunotherapy combinations: We have entered into collaboration agreements to evaluate the safety, tolerability and efficacy of surufatinib in combination with anti-PD-1 monoclonal antibodies, including with tislelizumab (BGB-A317, developed by BeiGene, Ltd.), Tuoyi® (toripalimab, developed by Shanghai Junshi Biosciences Co., Ltd.) and Tyvyt® (sintilimab, developed by Innovent Biologics, Inc.), which are approved in China.
Chi-Med (Nasdaq/AIM: HCM) is an innovative, commercial-stage, biopharmaceutical company committed, over the past twenty years, to the discovery and global development of targeted therapies and immunotherapies for the treatment of cancer and immunological diseases. It has a portfolio of nine cancer drug candidates currently in clinical studies around the world and extensive commercial infrastructure in its home market of China. For more information, please visit: www.chi-med.com.
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 regarding the therapeutic potential of surufatinib for the treatment of patients with pancreatic NET, the further clinical development of surufatinib in this and other indications, its expectations as to whether clinical studies of surufatinib 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 the sufficiency of its data to support NDA approval of surufatinib for the treatment of patients with pancreatic NET in China, its potential to gain expeditious approvals for surufatinib in other jurisdictions such as the U.S., E.U. or Japan, the safety profile of surufatinib, the potential for surufatinib to become a new standard of care for pancreatic NET patients, its ability to implement and complete its further clinical development plans for surufatinib, its potential commercial launch of surufatinib in China and other jurisdictions, the timing of these events, and the impact of the COVID-19 pandemic on general economic, regulatory and political conditions. 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.
Investor Enquiries |
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Mark Lee, Senior Vice President | +852 2121 8200 |
Annie Cheng, Vice President | +1 (973) 567 3786 |
Media Enquiries |
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Americas | |
Brad Miles, Solebury Trout | +1 (917) 570 7340 (Mobile) bmiles@troutgroup.com |
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Ben Atwell / Alex Shaw, FTI Consulting | +44 20 3727 1030 / +44 7771 913 902 (Mobile) / +44 7779 545 055 (Mobile) Chi-Med@fticonsulting.com |
Asia | |
Joseph Chi Lo, Brunswick | +852 9850 5033 (Mobile) jlo@brunswickgroup.com |
Zhou Yi, Brunswick | +852 9783 6894 (Mobile) yzhou@brunswickgroup.com |
Nominated Advisor |
|
Freddy Crossley / Atholl Tweedie, Panmure Gordon (UK) Limited |
+44 (20) 7886 2500 |
Hong Kong, Shanghai, & Florham Park, NJ: Friday, September 4, 2020: Hutchison China MediTech Limited (“Chi-Med”) (Nasdaq/AIM: HCM) has initiated FRESCO-2, a Phase III registration study of fruquintinib for the treatment of patients with metastatic colorectal cancer (“CRC”) in the U.S., Europe and Japan. The first patient was dosed on September 3, 2020, in the U.S.
FRESCO-2 is a randomized, double-blind, placebo-controlled, multicenter trial being conducted in patients with metastatic CRC. The primary endpoint of the study is overall survival. This large phase III trial will be enrolled in approximately 130 sites in 10 countries. Additional details of the study may be found at clinicaltrials.gov, using identifier NCT04322539.
The U.S. Food and Drug Administration (“FDA”) granted Fast Track Designation for the development of fruquintinib for the treatment of patients with metastatic CRC in June 2020. Clinical data including the completed Phase III FRESCO study in Chinese patients and this FRESCO-2 global study, if positive, would support a future New Drug Application (NDA) for the treatment of patients with advanced metastatic CRC (third-line and above), based on our agreement with the FDA. The FRESCO-2 study design was also reviewed and endorsed by the European Medicines Agency (EMA) and the Japanese Pharmaceuticals and Medical Devices Agency (PMDA).
CRC is cancer that starts in either the colon or rectum. CRC is the third most common cancer worldwide, causing more than 860,000 deaths in 2018.[1] In the U.S., it is estimated that 150,000 people will be diagnosed with CRC and 53,000 people will die from CRC in 2020.[2] In Europe, CRC is the second most common cancer, with an estimated 490,000 new cases and 240,000 deaths in 2018.[3] In Japan, CRC is the most common cancer, with an estimated 150,000 new cases and 57,000 deaths in 2018.[4]
Fruquintinib is a highly selective and potent oral inhibitor of vascular endothelial growth factor receptor (“VEGFR”) 1/2/3. VEGFR inhibitors play a pivotal role in blocking tumor angiogenesis. Fruquintinib was designed to improve kinase selectivity to minimize off-target toxicities, improve tolerability and provide more consistent target coverage. The generally good tolerability in patients to date, along with fruquintinib’s low potential for drug-drug interaction based on preclinical assessment, suggests that it may also be highly suitable for combinations with other anti-cancer therapies.
Chi-Med retains all rights to fruquintinib outside of China and is partnered with Eli Lilly and Company (“Lilly”) in China.
Fruquintinib was approved for marketing by the China National Medical Products Administration (NMPA) in September 2018 and commercially launched by Lilly in late November 2018 under the brand name Elunate®. Elunate® is for the treatment of patients with metastatic CRC that have been previously treated with fluoropyrimidine, oxaliplatin and irinotecan, including those who have previously received anti-VEGF therapy and/or anti-EGFR therapy (RAS wild type). Results of the FRESCO study, a Phase III pivotal registration trial of fruquintinib in 416 patients with metastatic CRC in China, were published in The Journal of the American Medical Association, JAMA, in June 2018 (clinicaltrials.gov identifier: NCT02314819).
In December 2017, Chi-Med initiated a multi-center, open-label, Phase I/Ib clinical study to evaluate the safety, tolerability and pharmacokinetics of fruquintinib in U.S. patients with advanced solid tumors (clinicaltrials.gov identifier: NCT03251378). Proof-of-concept cohorts in patients with metastatic CRC and metastatic breast cancer were added in 2019.
Gastric Cancer in China: In October 2017, Chi-Med initiated the FRUTIGA study, a randomized, double-blind, Phase III trial evaluating the efficacy and safety of fruquintinib combined with paclitaxel for second-line treatment of advanced gastric or esophagogastric junction (“GEJ”) adenocarcinoma. The trial is designed to enroll patients who did not respond to first-line standard chemotherapy. Subjects will receive either fruquintinib combined with paclitaxel or placebo combined with paclitaxel. Patients will be randomized at a 1:1 ratio and stratified according to factors such as stomach vs. GEJ tumor type and performance status. The primary efficacy endpoint is overall survival. Secondary efficacy endpoints include progression-free survival (as defined by RECIST 1.1), objective response rate, disease control rate, duration of response, and quality-of-life score (EORTC QLQ-C30, version 3.0). Biomarkers related to the antitumor activity of fruquintinib will also be explored (clinicaltrials.gov identifier NCT03223376). In June 2020, Chi-Med completed a planned interim data review. Based on the preset criteria, the Independent Data Monitoring Committee (IDMC) recommended that the trial continue.
Immunotherapy combinations: Chi-Med has entered into three collaboration agreements to evaluate the safety, tolerability and efficacy of fruquintinib in combination with programmed death-1 (PD-1) monoclonal antibodies, including with tislelizumab (BGB-A317, developed by BeiGene, Ltd.), Tyvyt® (sintilimab, IBI308, developed by Innovent Biologics, Inc.) and geptanolimab (GB226, developed by Genor Biopharma Co. Ltd.).
Chi-Med (Nasdaq/AIM: HCM) is an innovative, commercial-stage, biopharmaceutical company committed, over the past twenty years, to the discovery and global development of targeted therapies and immunotherapies for the treatment of cancer and immunological diseases. It has a portfolio of nine cancer drug candidates currently in clinical studies around the world and extensive commercial infrastructure in its home market of China. For more information, please visit: www.chi-med.com.
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 regarding the clinical development of fruquintinib in CRC in the United States, Europe and Japan, the potential therapeutic benefits of fruquintinib in CRC, Chi-Med’s clinical development plans for fruquintinib in other jurisdictions and indications as well as the growth of Chi-Med. 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 fruquintinib, including as a combination therapy, to meet the primary or secondary endpoint of a study, its ability to fund, implement and complete its further clinical development and commercialization plans for fruquintinib, the timing of these events, and the impact of the COVID-19 pandemic on general economic, regulatory and political conditions. In addition, as certain studies rely on the use of combination therapeutics with fruquintinib, such risks and uncertainties include assumptions regarding the safety, efficacy, supply and continued regulatory approval of such combination therapeutics. 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.
Investor Enquiries |
|
Mark Lee, Senior Vice President | +852 2121 8200 |
Annie Cheng, Vice President | +1 (973) 567 3786 |
Media Enquiries |
|
Americas | |
Brad Miles, Solebury Trout | +1 (917) 570 7340 (Mobile) bmiles@troutgroup.com |
Europe | |
Ben Atwell / Alex Shaw, FTI Consulting | +44 20 3727 1030 / +44 7771 913 902 (Mobile) / +44 7779 545 055 (Mobile) Chi-Med@fticonsulting.com |
Asia | |
Joseph Chi Lo, Brunswick | +852 9850 5033 (Mobile) jlo@brunswickgroup.com |
Zhou Yi, Brunswick | +852 9783 6894 (Mobile) yzhou@brunswickgroup.com |
Nominated Advisor |
|
Freddy Crossley / Atholl Tweedie, Panmure Gordon (UK) Limited |
+44 (20) 7886 2500 |
[1] Ferlay J, Ervik M, Lam F, Colombet M, Mery L, Piñeros M, Znaor A, Soerjomataram I, Bray F (2018). Global Cancer Observatory: Cancer Today. Lyon, France: International Agency for Research on Cancer. Available from: https://gco.iarc.fr/today
[2] SEER, Cancer Stat Facts: Colorectal Cancer. seer.cancer.gov/statfacts/html/colorect.html
[3] The Global Cancer Observatory, Europe fact sheet. gco.iarc.fr/today/data/factsheets/populations/908-europe-fact-sheets.pdf
[4] The Global Cancer Observatory, Japan fact sheet. gco.iarc.fr/today/data/factsheets/populations/392-japan-fact-sheets.pdf
Hong Kong, Shanghai, & Florham Park, NJ: Thursday, September 3, 2020: Hutchison China MediTech Limited (“Chi-Med”) (Nasdaq/AIM: HCM) has initiated a Phase II study of HMPL-453, its novel small molecule inhibitor targeting fibroblast growth factor receptors (“FGFR”), in patients with advanced intrahepatic cholangiocarcinoma (“IHCC”), which is a type of liver cancer.
The clinical study is a single-arm, multi-center, open-label study, evaluating the efficacy, safety and pharmacokinetics of HMPL-453 in patients with advanced IHCC with FGFR2 fusion that had failed at least one line of systemic therapy.
The primary outcome measure is objective response rate (ORR). Secondary outcome evaluations include preliminary efficacy measures, such as disease control rate (DCR), time to response (TTR), duration of response (DoR), progression-free survival (PFS), and overall survival (OS). Additional details may be found at clinicaltrials.gov, using identifier NCT04353375.
IHCC is a cancer that develops in the cells within the bile ducts[1]. With over 390,000 new cases every year, China accounted almost 50% of the world’s annual incidence of liver cancer in 2018.[2],[3] After hepatocellular carcinoma (“HCC”), IHCC is the second most common primary hepatic malignancy accounting for 10% to 20% of newly diagnosed liver cancers[4]. Approximately 10-15% of IHCC patients have tumors that harbor FGFR2 fusion[5],[6]. Long-term survival for patients with IHCC is worse than for HCC, which may be related to a high propensity for regional and distant metastases as well as the lack of effective systemic therapy options[4].
FGFRs are a sub‑family of receptor tyrosine kinases. Activation of FGFR signaling pathways is central to several biological processes. In normal physiology, FGF/FGFR signaling is involved in embryonic development (organogenesis and morphogenesis), tissue repair, angiogenesis, neuroendocrine and metabolism homeostasis. Given its complexity and critical role in a number of important physiological processes, aberrant FGFR signaling has been found to be a driving force in tumor growth, promotion of angiogenesis, as well as conferring resistance to anti‑tumor therapies.
HMPL‑453 is a novel, highly selective and potent small molecule inhibitor targeting FGFR 1, 2 and 3. In pre‑clinical studies, HMPL‑453 demonstrated superior potency and better kinase selectivity as compared to other drugs in the same class, as well as a favorable safety profile. Enrollment has been completed for the dose escalation of the Phase I study of HMPL-453 in China (clinicaltrials.gov identifier NCT03160833). Enrollment of a Phase II study is ongoing in patients with advanced malignant mesothelioma in China (clinicaltrials.gov identifier NCT04290325).
Chi-Med (Nasdaq/AIM: HCM) is an innovative, commercial-stage, biopharmaceutical company committed, over the past twenty years, to the discovery and global development of targeted therapies and immunotherapies for the treatment of cancer and immunological diseases. It has a portfolio of nine cancer drug candidates currently in clinical studies around the world and extensive commercial infrastructure in its home market of China. For more information, please visit: www.chi-med.com.
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-453, including plans to initiate clinical studies for HMPL-453, 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-453 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-453 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.
Investor Enquiries |
|
Mark Lee, Senior Vice President | +852 2121 8200 |
Annie Cheng, Vice President | +1 (973) 567 3786 |
Media Enquiries |
|
Americas | |
Brad Miles, Solebury Trout | +1 (917) 570 7340 (Mobile) bmiles@troutgroup.com |
Europe | |
Ben Atwell / Alex Shaw, FTI Consulting | +44 20 3727 1030 / +44 7771 913 902 (Mobile) / +44 7779 545 055 (Mobile) Chi-Med@fticonsulting.com |
Asia | |
Joseph Chi Lo, Brunswick | +852 9850 5033 (Mobile) jlo@brunswickgroup.com |
Zhou Yi, Brunswick | +852 9783 6894 (Mobile) yzhou@brunswickgroup.com |
Nominated Advisor |
|
Freddy Crossley / Atholl Tweedie, Panmure Gordon (UK) Limited |
+44 (20) 7886 2500 |
[1] NIH. Genetic & Rare Diseases Information Center. rarediseases.info.nih.gov/diseases/6042/intrahepatic-cholangiocarcinoma.
[2] Global Cancer Observatory. China Fact Sheet. gco.iarc.fr/today/data/factsheets/populations/160-china-fact-sheets.pdf.
[3] Global Cancer Observatory. Liver Cancer Fact Sheet. gco.iarc.fr/today/data/factsheets/cancers/11-Liver-fact-sheet.pdf.
[4] Epidemiology of Hepatocellular Carcinoma and Intrahepatic Cholangiocarcinoma. Cancer Control. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5937247.
[5] Lowery et al. Comprehensive Molecular Profiling of Intrahepatic and Extrahepatic Cholangiocarcinomas: Potential Targets for Intervention. Clin Cancer Res September 1 2018 (24) (17) 4154-4161. DOI: 10.1158/1078-0432.CCR-18-0078.
[6] Cleary et al. Therapeutic targeting of extracellular FGFR2 activating deletions in intrahepatic cholangiocarcinoma. J Clin Oncol 38, 2020 (suppl 4; abstr 567). DOI: 10.1200/JCO.2020.38.4_suppl.567.
Date: Sep 15, 2020 (Tuesday) |
Time: 8:40am EDT (1:40pm BST/8:40pm HKT) |