1stOncology™: Cancer Intelligence Service – Page 11735 – 1stOncology is recognized as a Top 10 Global Pharma Analytic Provider

Castle Biosciences Announces Study Establishing the Value of Integrating DecisionDx-SCC Test into Management of High-Risk Cutaneous Squamous Cell Carcinoma

On January 20, 2020 Castle Biosciences, Inc. (Nasdaq: CSTL), a skin cancer diagnostics company providing personalized genomic information to improve cancer treatment decisions, reported the presentation of clinical utility data for its cutaneous squamous cell carcinoma (SCC) prognostic test, DecisionDx-SCC, for patients diagnosed with high-risk cutaneous SCC (Press release, Castle Biosciences, JAN 20, 2020, View Source [SID1234553344]). The test is expected to be launched commercially in the second half of 2020.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

Schedule Your 30 min Free Demo!

The poster titled, "Integrating the 40-Gene Expression Profile (40-GEP) Test into Management of High-Risk Cutaneous Squamous Cell Carcinoma," was presented during the 2020 Winter Clinical Dermatology Conference, January 17-22 in Hawaii.

The data presented support a framework for integration of DecisionDx-SCC into risk-appropriate management of high-risk cutaneous SCC patients (as defined by the National Comprehensive Cancer Network [NCCN]).

Disease and Study Background

Approximately 1 million patients are diagnosed with cutaneous SCC in the U.S. each year, and the incidence continues to grow.
As with other cancer types, NCCN guidelines define treatment pathways based on risk of metastasis. In the case of cutaneous SCC, there are two clinicopathologically defined categories: low-risk and high-risk.
The Company believes two important issues exist in implementing a high-risk treatment pathway. First, the NCCN risk criteria, as well as available staging systems, have low positive predictive value (PPV) – meaning that the majority of high-risk patients do not develop metastasis; and, second, the high-risk treatment pathways are broad.
The clinical implication being that many patients categorized as high risk, but who have a low biological risk of metastasis, may be overtreated with radiation, chemotherapy or other interventions; and those patients categorized as high risk and who also have a high biological risk of metastasis may be undertreated if clinical decisions are to follow a conservative treatment plan within the broad boundaries of NCCN high-risk pathways.
The Company believes improved stratification for implementation of risk-appropriate treatment plans for patients within NCCN-defined high-risk cutaneous SCC is needed. NCCN defines high risk as cutaneous SCC patients with a single high-risk feature, e.g., immunodeficiency; tumor diameter greater than or equal to 2cm; any tumor of the mask area, genitals, hands, or feet; or poor tumor differentiation.
DecisionDx-SCC was developed and validated to stratify risk of regional or distant metastasis at three years after diagnosis in high-risk cutaneous SCC patients, classifying patients as low (Class 1), high (Class 2A) or highest (Class 2B) risk of metastasis.
This study was designed to evaluate the integration of DecisionDx-SCC (40-GEP test) with AJCC and Brigham and Women’s Hospital (BWH) T stage criteria into management of 300 NCCN high-risk cutaneous SCC patients.
Within the broad framework of NCCN recommendations for high-risk cutaneous SCC, the aim is to identify those high-risk patients who would be eligible for a conservative, reduced treatment plan, thus avoiding unnecessary adjuvant interventions, and identifying those patients who would most benefit from aggressive adjuvant treatment strategies.
Study Findings

Integration of DecisionDx-SCC for NCCN-defined high-risk cutaneous SCC patients with T staging identified a group of 159 patients (Class 1, T1-T2) with a 7.5% rate of metastasis, which approaches that of the general cutaneous SCC patient population. A low intensity management strategy, within the broad NCCN high-risk guidelines, could spare this patient group unnecessary adjuvant procedures and potential adverse effects.
Conversely, those patients (n=24) with rates of metastasis surpassing 50% (Class 2B), regardless of AJCC or BWH T stage, would warrant a high intensity strategy, also within the broad NCCN high-risk guidelines, that increases follow-up visits, utilizes imaging and/or biopsies for nodal assessment, and offers adjuvant treatments and clinical trials for probable metastatic events.
The data support a framework for risk-aligned treatment plans when DecisionDx-SCC is incorporated into management of NCCN high-risk cutaneous SCC patients.
"There is a clear need to improve identification of true high-risk and lower-risk patients diagnosed with high-risk cutaneous SCC, so that risk-directed treatment plans can be implemented," said Aaron Farberg, M.D., study investigator, Icahn School of Medicine at Mount Sinai, New York and Arkansas Dermatology Skin Cancer Center, Little Rock, Arkansas. "Clinical use of DecisionDx-SCC, along with current staging systems, may better identify patients with cutaneous SCC at high risk for metastasis and enable more informed clinical decisions regarding adjuvant therapy and other management options."

The DecisionDx-SCC test is the second skin cancer test discovered, developed and validated by Castle Biosciences.

About Cutaneous Squamous Cell Carcinoma

Cutaneous squamous cell carcinoma (SCC), a nonmelanoma skin cancer, is one of the most common cancers. Approximately 1,000,000 patients are diagnosed with cutaneous SCC each year in the U.S. Most patients have a favorable prognosis, but a subset of patients will develop metastasis, and up to 15,000 patients each year die from their disease, exceeding the number of deaths from cutaneous melanoma. As current staging parameters have a low positive predictive value, many more patients are considered high risk than actually develop metastatic disease. Conversely, many patients who develop metastatic disease are misidentified as low risk. This may lead to over and undertreatment of a substantial number of cutaneous SCC patients. To address this clinical need, Castle Biosciences has developed a gene expression profile test designed to improve upon current staging systems and identify patients with cutaneous SCC at high risk for metastasis or recurrence, in order to enable more informed clinical decisions regarding adjuvant therapy and other management options.

Janssen Seeks Expanded Use of IMBRUVICA® (ibrutinib) in Combination with Rituximab for Patients with Previously Untreated Chronic Lymphocytic Leukaemia (CLL)

On January 20, 2020 The Janssen Pharmaceutical Companies of Johnson & Johnson reported the submission of a Type II variation application to the European Medicines Agency (EMA) seeking to expand the label of IMBRUVICA (ibrutinib) to include ibrutinib in combination with rituximab for the first-line treatment of patients with chronic lymphocytic leukaemia (CLL) (Press release, Johnson & Johnson, JAN 20, 2020, View Source [SID1234553343]).

The submission is supported by data from the Phase 3 E1912 study, designed and conducted in the United States (U.S.) by the ECOG-ACRIN Cancer Research Group (ECOG-ACRIN) and sponsored by the National Cancer Institute (NCI), which is part of the U.S. National Institutes of Health. The study evaluated 529 patients with previously untreated CLL aged 70 years or younger, who were randomly assigned in a 2:1 ratio to receive ibrutinib plus rituximab (n=354) or the chemo-immunotherapy FCR (n=175). The primary endpoint was progression-free survival (PFS) and one of the secondary endpoints was overall survival (OS).1 The primary study results were previously published in The New England Journal of Medicine, and the extended four-year median follow-up results were presented at the 2019 American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting.1,2

"The ECOG-ACRIN’s E1912 study demonstrated that ibrutinib in combination with rituximab has shown superior PFS and OS versus FCR, a chemotherapy-based standard of care for younger patients with newly diagnosed CLL," said Dr Patrick Laroche, Haematology Therapy Area Lead, Europe, Middle East and Africa (EMEA), Janssen-Cilag. "We look forward to working with regulatory authorities to bring ibrutinib to more patients with CLL who may benefit from treatment."

"The E1912 study demonstrated the important clinical benefit of ibrutinib in combination with rituximab in the frontline setting," said Craig Tendler, M.D., Vice President, Clinical Development and Global Medical Affairs, Janssen Research & Development, LLC. "We remain committed to replacing long-standing use of chemotherapy with ibrutinib-based combination regimens for the treatment of patients with CLL in the frontline setting."

About ibrutinib

Ibrutinib is a once-daily, first-in-class Bruton’s tyrosine kinase (BTK) inhibitor that is administered orally.3 Ibrutinib blocks the BTK protein; the BTK protein sends important signals that tell B cells to mature and produce antibodies. BTK signaling is needed by specific cancer cells to multiply and spread.4 By blocking BTK, ibrutinib may help move abnormal B cells out of their nourishing environments in the lymph nodes, bone marrow, and other organs.5

Ibrutinib is currently approved in Europe for:3

Chronic lymphocytic leukaemia (CLL): As a single agent or in combination with obinutuzumab for the treatment of adult patients with previously untreated CLL, and as a single agent or in combination with bendamustine and rituximab (BR) for the treatment of adult patients with CLL who have received at least one prior therapy
Mantle cell lymphoma (MCL): As a single agent for the treatment of adult patients with relapsed or refractory MCL
Waldenström’s macroglobulinemia (WM): As a single agent for the treatment of adult patients who have received at least one prior therapy or in first-line treatment for patients unsuitable for chemo-immunotherapy, and in combination with rituximab for the treatment of adult patients
Ibrutinib is approved in more than 95 countries for at least one indication, and to date, has been used to treat more than 170,000 patients worldwide across its approved indications.6

The most common adverse reactions seen with ibrutinib include diarrhoea, neutropenia, haemorrhage (e.g., bruising), musculoskeletal pain, nausea, rash, and pyrexia.3

For a full list of side effects and information on dosage and administration, contraindications and other precautions when using ibrutinib please refer to the Summary of Product Characteristics for further information.

About chronic lymphocytic leukaemia

Chronic lymphocytic leukaemia (CLL) is typically a slow-growing blood cancer of the white blood cells.7 The overall incidence of CLL in Europe is approximately 4.92 cases per 100,000 persons per year and is about 1.5 times more common in men than in women.8 CLL is predominantly a disease of the elderly, with a median age of 72 years at diagnosis.9

The disease eventually progresses in the majority of patients, and they are faced with fewer treatment options with each relapse. Patients are often prescribed multiple lines of therapy as they relapse or become resistant to treatments.

Genmab Announces European Marketing Authorization for DARZALEX® (Daratumumab) in Combination with Bortezomib, Thalidomide and Dexamethasone in Frontline Multiple Myeloma

On January 20, 2020 Genmab A/S (Nasdaq: GMAB) reported that the European Commission (EC) has granted marketing authorization for DARZALEX (daratumumab) in combination with bortezomib, thalidomide and dexamethasone for the treatment of adult patients with newly diagnosed multiple myeloma who are eligible for autologous stem cell transplant (ASCT) (Press release, Genmab, JAN 20, 2020, View Source [SID1234553341]). The EC approval follows a positive opinion issued for DARZALEX by the CHMP of the European Medicines Agency (EMA) in December 2019. In August 2012, Genmab granted Janssen Biotech, Inc. (Janssen) an exclusive worldwide license to develop, manufacture and commercialize daratumumab.

"With this approval, newly diagnosed patients with multiple myeloma who are eligible for ASCT may have the opportunity for treatment with a DARZALEX-containing regimen. We are extremely pleased that DARZALEX has received this latest approval and we look forward to the combination of DARZALEX plus bortezomib, thalidomide and dexamethasone being launched in Europe," said Jan van de Winkel, Ph.D., Chief Executive Officer of Genmab.

The approval was based on the Phase III CASSIOPEIA (MMY3006) study sponsored by the French Intergroupe Francophone du Myelome (IFM) in collaboration with the Dutch-Belgian Cooperative Trial Group for Hematology Oncology (HOVON) and Janssen R&D, LLC. Data from this study was published in The Lancet and presented at the 2019 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting.

About the CASSIOPEIA (MMY3006) study
This Phase III study is a randomized, open-label, multicenter study, run by the French Intergroupe Francophone du Myelome (IFM) in collaboration with the Dutch-Belgian Cooperative Trial Group for Hematology Oncology (HOVON) and Janssen R&D, LLC, including 1,085 newly diagnosed subjects with previously untreated symptomatic multiple myeloma who are eligible for high dose chemotherapy and stem cell transplant. In the first part of the study, patients were randomized to receive induction and consolidation treatment with daratumumab combined with bortezomib, thalidomide (an immunomodulatory agent) and dexamethasone (a corticosteroid) or treatment with bortezomib, thalidomide and dexamethasone alone. The primary endpoint is the proportion of patients that achieve a stringent Complete Response (sCR). In the second part of the study, patients that achieved a response will undergo a second randomization to either receive maintenance treatment of daratumumab 16 mg/kg every 8 weeks for up to 2 years versus no further treatment (observation). The primary endpoint of this part of the study is progression free survival (PFS).

About multiple myeloma
Multiple myeloma is an incurable blood cancer that starts in the bone marrow and is characterized by an excess proliferation of plasma cells.1 Approximately 16,830 new patients were expected to be diagnosed with multiple myeloma and approximately 10,480 people were expected to die from the disease in the Western Europe in 2018.2 Globally, it was estimated that 160,000 people were diagnosed and 106,000 died from the disease in 2018.3 While some patients with multiple myeloma have no symptoms at all, most patients are diagnosed due to symptoms which can include bone problems, low blood counts, calcium elevation, kidney problems or infections.4

About DARZALEX(daratumumab)
DARZALEX (daratumumab) intravenous infusion is indicated for the treatment of adult patients in the United States: in combination with bortezomib, thalidomide and dexamethasone as treatment for patients newly diagnosed with multiple myeloma who are eligible for autologous stem cell transplant; in combination with lenalidomide and dexamethasone for the treatment of patients with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplant; in combination with bortezomib, melphalan and prednisone for the treatment of patients with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplant; in combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone, for the treatment of patients with multiple myeloma who have received at least one prior therapy; in combination with pomalidomide and dexamethasone for the treatment of patients with multiple myeloma who have received at least two prior therapies, including lenalidomide and a proteasome inhibitor (PI); and as a monotherapy for the treatment of patients with multiple myeloma who have received at least three prior lines of therapy, including a PI and an immunomodulatory agent, or who are double-refractory to a PI and an immunomodulatory agent.5 DARZALEX is the first monoclonal antibody (mAb) to receive U.S. Food and Drug Administration (U.S. FDA) approval to treat multiple myeloma. DARZALEX intravenous infusion is indicated for the treatment of adult patients in Europe: in combination with bortezomib, thalidomide and dexamethasone as treatment for patients newly diagnosed with multiple myeloma who are eligible for autologous stem cell transplant; in combination with lenalidomide and dexamethasone for the treatment of patients with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplant; in combination with bortezomib, melphalan and prednisone for the treatment of adult patients with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplant; for use in combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone, for the treatment of adult patients with multiple myeloma who have received at least one prior therapy; and as monotherapy for the treatment of adult patients with relapsed and refractory multiple myeloma, whose prior therapy included a PI and an immunomodulatory agent and who have demonstrated disease progression on the last therapy6. The option to split the first infusion of DARZALEX over two consecutive days has been approved in both Europe and the U.S. In Japan, DARZALEX intravenous infusion is approved for the treatment of adult patients: in combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone for the treatment of relapsed or refractory multiple myeloma; in combination with bortezomib, melphalan and prednisone for the treatment of patients with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplant; in combination with lenalidomide and dexamethasone for the treatment of patients with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplant. DARZALEX is the first human CD38 monoclonal antibody to reach the market in the United States, Europe and Japan. For more information, visit www.DARZALEX.com.

Daratumumab is a human IgG1k monoclonal antibody (mAb) that binds with high affinity to the CD38 molecule, which is highly expressed on the surface of multiple myeloma cells. Daratumumab triggers a person’s own immune system to attack the cancer cells, resulting in rapid tumor cell death through multiple immune-mediated mechanisms of action and through immunomodulatory effects, in addition to direct tumor cell death, via apoptosis (programmed cell death).5,6,7,8,9,10

Daratumumab is being developed by Janssen Biotech, Inc. under an exclusive worldwide license to develop, manufacture and commercialize daratumumab from Genmab. A comprehensive clinical development program for daratumumab is ongoing, including multiple Phase III studies in smoldering, relapsed and refractory and frontline multiple myeloma settings. Additional studies are ongoing or planned to assess the potential of daratumumab in other malignant and pre-malignant diseases in which CD38 is expressed, such as amyloidosis, NKT-cell lymphoma and B-cell and T-cell ALL. Daratumumab has received two Breakthrough Therapy Designations from the U.S. FDA for certain indications of multiple myeloma, including as a monotherapy for heavily pretreated multiple myeloma and in combination with certain other therapies for second-line treatment of multiple myeloma.

Evotec SE: Increase of profitability guidance for financial year 2019

On January 20, 2020 Evotec SE (Frankfurt Stock Exchange; EVT, MDAX/TecDAX, ISIN: DE0005664809, WKN 566480) reported an increase in its profitability guidance for the financial year 2019 after the preliminary completion of the latest evaluation of the Company’s financial performance (Press release, Evotec, JAN 20, 2020, View Source;announcements/ad-hoc-releases/p/evotec-se-increase-of-profitability-guidance-for-financial-year-2019-5901 [SID1234553340]).

Based on the preliminary unaudited consolidated results for the financial year 2019, the Company now expects an increase of the adjusted Group EBITDA* by more than 25% (previously: improve by approx. 15%) for 2019 compared to previous year (2018: € 92.0 m). The positive adjustment of the guidance is primarily due to a strong operating performance in the fourth quarter of 2019 and unexpectedly high milestone revenues from long-term partnerships such as those with Celgene, Bayer and Sanofi in December 2019, which in particular needed to be clarified in terms of revenue recognition and the corresponding allocation to the 2019 or 2020 financial year.

All other elements of the Company’s financial guidance are confirmed.

*(EBITDA excludes contingent considerations, income from bargain purchase and excl. impairments on goodwill, other intangible and tangible assets as well as the total non-operating result)

Chi-Med Announces that Surufatinib Phase III SANET-p Study Has Already Achieved its Primary Endpoint in Advanced Pancreatic Neuroendocrine Tumors in China and Will Stop Early

On January 20, 2020 Hutchison China MediTech Limited ("Chi-Med") (AIM/Nasdaq: HCM) reported that the independent Data Monitoring Committee ("IDMC") of the Phase III pivotal study of surufatinib in advanced neuroendocrine tumors – pancreatic ("SANET-p") has completed a pre-planned interim analysis (Press release, Hutchison China MediTech, JAN 20, 2020, https://www.chi-med.com/surufatinib-phase-iii-sanet-p-study-achieved-primary-endpoint/ [SID1234553338]). The IDMC recommended that the study stops early as the pre-defined primary endpoint of progression free survival ("PFS") had already been met.

Following the early success of this study, Chi-Med now plans to arrange a pre-New Drug Application ("NDA") meeting with the China National Medical Products Administration ("NMPA") to discuss the preparation of the NDA for surufatinib for this indication. Chi-Med intends to submit the results of the SANET-p study for presentation at an upcoming scientific conference.

Christian Hogg, Chief Executive Officer of Chi-Med, said, "This positive data is a further important milestone for Chi-Med. Following surufatinib’s NDA submission for the treatment of non-pancreatic neuroendocrine tumors, these positive results for pancreatic neuroendocrine tumors reinforce that surufatinib has the unique opportunity to address all advanced neuroendocrine tumors. We believe that no targeted therapies are approved in China or globally for such a broad spectrum of neuroendocrine tumor disease."

In November 2019, the U.S. Food and Drug Administration ("FDA") granted Orphan Drug designation to surufatinib for the treatment of pancreatic neuroendocrine tumors. The China NDA for surufatinib for the treatment of advanced non-pancreatic neuroendocrine tumors was accepted for review by the NMPA, and was subsequently granted Priority Review status in December. Currently Chi-Med is building an oncology-focused sales and marketing team to launch surufatinib if approved in China.

About SANET-p
SANET-p is a Phase III study in China of surufatinib in patients with low-grade or intermediate-grade advanced pancreatic neuroendocrine tumor patients for whom there is no effective therapy. In this study, patients are randomized at a 2:1 ratio to receive either 300 mg of surufatinib orally daily or placebo, on a 28-day treatment cycle. The primary endpoint of the study is to evaluate the PFS, with secondary endpoints including objective response rate (ORR), disease control rate (DCR), time to response (TTR), duration of response (DoR), overall survival (OS), safety, and tolerability. Additional details may be found at clinicaltrials.gov, using identifier NCT02589821.

About Neuroendocrine Tumors
Neuroendocrine tumors 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. Neuroendocrine tumors are typically classified as pancreatic neuroendocrine tumors or non-pancreatic neuroendocrine tumors. Approved targeted therapies include Sutent and Afinitor for pancreatic neuroendocrine tumors, or well-differentiated, non-functional gastrointestinal or lung neuroendocrine tumors.

According to Frost and Sullivan, there were 19,000 newly diagnosed cases of neuroendocrine tumors in the U.S. in 2018. Importantly, neuroendocrine tumors 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 neuroendocrine tumors in the U.S. in 2018 of which over 90%, or approximately 132,000, were non-pancreatic neuroendocrine tumor patients.

In China, there were approximately 67,600 newly diagnosed neuroendocrine tumor 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[1]. It is estimated that approximately 80% of the patients living with neuroendocrine tumors in China are non-pancreatic neuroendocrine tumor patients.

About Surufatinib
Surufatinib (previously known as HMPL-012 or sulfatinib) 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. Surufatinib is in several late-stage and proof-of-concept clinical trials in China and proof-of-concept clinical trials in the U.S.

According to Frost & Sullivan, the market for anti-angiogenesis VEGF/VEGFR inhibitors in China has grown from US$500 million in 2015 to over US$1.5 billion in 2019 and is expected to reach US$5 billion by 2026.

Chi-Med currently retains all rights to surufatinib worldwide.

Non-pancreatic neuroendocrine tumors in China: In November 2019, an NDA for surufatinib for the treatment of patients with advanced non-pancreatic neuroendocrine tumors was accepted for review by the China NMPA. The NDA is supported by data from the successful SANET-ep study, a Phase III study of surufatinib in advanced neuroendocrine tumors – extra-pancreatic patients 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 European Society for Medical Oncology Congress on September 29, 2019. (clinicaltrials.gov identifier: NCT02588170).

Pancreatic neuroendocrine tumors 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 neuroendocrine tumors in China. The primary endpoint is PFS (clinicaltrials.gov identifier: NCT02589821).

Pancreatic neuroendocrine tumors in the U.S. and Europe: We are planning a U.S. registration study in neuroendocrine tumor patients based on the encouraging data from the Phase II and Phase III studies of surufatinib in neuroendocrine tumors in China (clinicaltrials.gov identifier: NCT02267967), and the ongoing Phase Ib study in the U.S. (clinicaltrials.gov identifier: NCT02549937). This program was granted Orphan Drug designation by the U.S. FDA.

Biliary tract cancer in China: In March 2019, we initiated a Phase IIb/III study comparing surufatinib (HMPL-012 or sulfatinib) with capecitabine in patients with advanced biliary tract cancer whose disease progressed on first-line chemotherapy. The primary endpoint is OS (clinicaltrials.gov identifier NCT03873532).

Immunotherapy combinations: In November 2018 and September 2019, we entered into collaboration agreements to evaluate the safety, tolerability and efficacy of surufatinib in combination with anti-programmed cell death protein 1 (PD-1) monoclonal antibodies. This included global collaborations to evaluate the combination of surufatinib with Tuoyi, approved in China by Shanghai Junshi Biosciences Co. Ltd, and with Tyvyt, approved in China by Innovent Biologics, Inc.