Daiichi Sankyo Submits Supplemental New Drug Application for Trastuzumab Deruxtecan in Japan for Treatment of Patients with HER2 Positive Metastatic Gastric Cancer
Daiichi Sankyo Company, Limited (hereafter, Daiichi Sankyo) today announced that it has submitted a supplemental New Drug Application (sNDA) to Japan’s Ministry of Health, Labour and Welfare (MHLW) for trastuzumab deruxtecan (DS-8201), a HER2 directed antibody drug conjugate (ADC), for the treatment of patients with HER2 positive metastatic gastric cancer.
Trastuzumab deruxtecan has previously received SAKIGAKE designation for this second potential indication and will receive an expedited review time of six months. Currently, there are no HER2 directed treatment options approved for patients with HER2 positive metastatic gastric cancer who have progressed after trastuzumab.
"Today’s submission by Daiichi Sankyo brings us closer to bringing trastuzumab deruxtecan to a population of patients with unmet medical need in Japan,” said Wataru Takasaki, PhD, Executive Officer, Head of R&D Division in Japan, Daiichi Sankyo. “If approved, trastuzumab deruxtecan has the potential to meaningfully advance the treatment of patients with HER2 positive metastatic gastric cancer as the first ever antibody drug conjugate approved to treat this type of cancer.”
The Japan sNDA is based on data from the pivotal phase 2 DESTINY-Gastric01 trial and phase 1 trial published in The Lancet Oncology. In DESTINY-Gastric01, patients treated with trastuzumab deruxtecan demonstrated a statistically significant and clinically meaningful improvement in objective response rate (ORR) as assessed by an independent review committee as well as in overall survival (OS) compared to patients treated with investigator’s choice of chemotherapy (irinotecan or paclitaxel monotherapy). The full results of DESTINY-Gastric01 will be presented at the 2020 American Society of Clinical Oncology Annual Meeting.
The overall safety and tolerability profile of trastuzumab deruxtecan in DESTINY-Gastric01 was consistent with that seen in the phase 1 trial in which the most common adverse events (≥30 percent, any grade) were hematologic and gastrointestinal including neutrophil count decrease, anemia, nausea and decreased appetite. There were cases of drug-related interstitial lung disease (ILD) and pneumonitis, the majority of which were grade 1 and 2 with two grade 3 and one grade 4. No ILD-related deaths (grade 5) occurred in patients with gastric cancer in the phase 1 trial or in the DESTINY-Gastric01 trial.
Accelerated approval in the U.S. and approval in Japan under the conditional early approval system were recently received for trastuzumab deruxtecan for the treatment of adult patients with unresectable or metastatic HER2 positive breast cancer who have received two or more prior anti-HER2 based regimens.
HER2 is a cell growth-promoting tyrosine kinase receptor protein expressed on the surface of many types of tumors including gastric, breast and lung cancers. HER2 overexpression is associated with a specific HER2 gene alteration known as HER2 amplification and is often associated aggressive disease and poorer prognosis.1
About Gastric Cancer
Gastric (stomach) cancer is the fifth most common cancer worldwide and the third leading cause of cancer mortality; there were approximately one million new cases reported in 2018 and 783,000 deaths.2 Incidence rates for gastric cancer are markedly higher in eastern Asia, where approximately half of all cases occur.2 South Korea and Japan have the first and third highest incidence rates of gastric cancer worldwide, respectively; in 2018, the age-standardized rate in Japan was 27.5 per 100,000 and in South Korea it was 39.6 per 100,000.3
Approximately one in five gastric cancers are HER2 positive.4 Gastric cancer is usually diagnosed in the advanced stage, but even when diagnosed in earlier stages of the disease the survival rate remains modest.5 Recommended first-line treatment for HER2 positive advanced or metastatic gastric cancer is combination chemotherapy plus trastuzumab, an anti-HER2 medicine, which has been shown to improve outcomes when added to chemotherapy.6 For gastric cancer that progresses on first line treatment, trastuzumab has not shown any further benefit and there are no other approved HER2 targeting medicines.6
DESTINY-Gastric01 is a pivotal phase 2, open-label, multi-center study assessing the safety and efficacy of trastuzumab deruxtecan in 189 patients from Japan and South Korea with HER2 expressing advanced gastric cancer or gastroesophageal junction adenocarcinoma (defined as IHC3+ or IHC2+/ISH+) who have progressed on two or more prior regimens including fluoropyrimidine (5-FU), platinum chemotherapy and trastuzumab. Patients were randomized 2:1 to receive trastuzumab deruxtecan or investigator’s choice of chemotherapy (paclitaxel or irinotecan monotherapy). Patients were treated with trastuzumab deruxtecan 6.4 mg/kg once every three weeks or chemotherapy given on the same schedule. The primary endpoint of the study is ORR. Secondary endpoints include OS, progression-free survival, duration of response, disease control rate and time to treatment failure.
About Trastuzumab Deruxtecan
Trastuzumab deruxtecan (formerly known as DS-8201; trastuzumab deruxtecan outside the U.S.; fam- trastuzumab deruxtecan-nxki in the U.S. only) is a HER2 directed ADC and is the lead ADC in the oncology portfolio of Daiichi Sankyo and the most advanced program in AstraZeneca’s ADC Scientific platform.
ADCs are targeted cancer medicines that deliver cytotoxic chemotherapy (“payload”) to cancer cells via a linker attached to a monoclonal antibody that binds to a specific target expressed on cancer cells. Designed using Daiichi Sankyo’s proprietary DXd ADC technology, trastuzumab deruxtecan is comprised of a HER2 monoclonal antibody attached to a novel topoisomerase I inhibitor payload by a tetrapeptide-based linker.
Trastuzumab deruxtecan has not been approved in the EU, or countries outside of Japan and the United States, for any indication. It is an investigational agent globally for various indications. Safety and effectiveness have not been established for the subject proposed use.
About the Trastuzumab Deruxtecan Clinical Development Program
A comprehensive development program for trastuzumab deruxtecan is underway globally with six pivotal trials evaluating the efficacy and safety of trastuzumab deruxtecan monotherapy across multiple HER2 driven cancers including breast, gastric, colorectal and lung cancers. Trials in combination with other anticancer treatments, such as immunotherapy, also are underway.
About the Collaboration between Daiichi Sankyo and AstraZeneca
In March 2019, Daiichi Sankyo and AstraZeneca entered into a global collaboration to jointly develop and commercialize trastuzumab deruxtecan worldwide, except in Japan where Daiichi Sankyo maintains exclusive rights. Daiichi Sankyo is solely responsible for the manufacturing and supply.
U.S. FDA-Approved Indication for ENHERTU
ENHERTU is a HER2-directed antibody and topoisomerase inhibitor conjugate indicated for the treatment of adult patients with unresectable or metastatic HER2-positive breast cancer who have received two or more prior anti-HER2-based regimens in the metastatic setting.
This indication is approved under accelerated approval based on tumor response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.
WARNING: INTERSTITIAL LUNG DISEASE and EMBRYO-FETAL TOXICITY
WARNINGS AND PRECAUTIONS
Interstitial Lung Disease / Pneumonitis
Severe, life-threatening, or fatal interstitial lung disease (ILD), including pneumonitis, can occur in patients treated with ENHERTU. In clinical studies, of the 234 patients with unresectable or metastatic HER2- positive breast cancer treated with ENHERTU, ILD occurred in 9% of patients. Fatal outcomes due to ILD and/or pneumonitis occurred in 2.6% of patients treated with ENHERTU. Median time to first onset was 4.1 months (range: 1.2 to 8.3).
Advise patients to immediately report cough, dyspnea, fever, and/or any new or worsening respiratory symptoms. Monitor patients for signs and symptoms of ILD. Promptly investigate evidence of ILD. Evaluate patients with suspected ILD by radiographic imaging. Consider consultation with a pulmonologist. For asymptomatic ILD/pneumonitis (Grade 1), interrupt ENHERTU until resolved to Grade 0, then if resolved in ≤28 days from date of onset, maintain dose. If resolved in >28 days from date of onset, reduce dose one level. Consider corticosteroid treatment as soon as ILD/pneumonitis is suspected (e.g., ≥0.5 mg/kg prednisolone or equivalent). For symptomatic ILD/pneumonitis (Grade 2 or greater), permanently discontinue ENHERTU. Promptly initiate corticosteroid treatment as soon as ILD/pneumonitis is suspected (e.g., ≥1 mg/kg prednisolone or equivalent). Upon improvement, follow by gradual taper (e.g., 4 weeks).
Severe neutropenia, including febrile neutropenia, can occur in patients treated with ENHERTU. Of the 234 patients with unresectable or metastatic HER2-positive breast cancer who received ENHERTU, a decrease in neutrophil count was reported in 30% of patients and 16% had Grade 3 or 4 events. Median time to first onset was 1.4 months (range: 0.3 to 18.2). Febrile neutropenia was reported in 1.7% of patients.
Monitor complete blood counts prior to initiation of ENHERTU and prior to each dose, and as clinically indicated. Based on the severity of neutropenia, ENHERTU may require dose interruption or reduction. For Grade 3 neutropenia (Absolute Neutrophil Count [ANC] <1.0 to 0.5 x>9/L) interrupt ENHERTU until resolved to Grade 2 or less, then maintain dose. For Grade 4 neutropenia (ANC <0.5 x>9/L) interrupt ENHERTU until resolved to Grade 2 or less. Reduce dose by one level. For febrile neutropenia (ANC <1.0 x>9/L and temperature >38.3ºC or a sustained temperature of ≥38ºC for more than 1 hour), interrupt ENHERTU until resolved. Reduce dose by one level. 1.0>0.5>1.0>
Left Ventricular Dysfunction
Patients treated with ENHERTU may be at increased risk of developing left ventricular dysfunction. Left ventricular ejection fraction (LVEF) decrease has been observed with anti-HER2 therapies, including ENHERTU. In the 234 patients with unresectable or metastatic HER2-positive breast cancer who received ENHERTU, two cases (0.9%) of asymptomatic LVEF decrease were reported. Treatment with ENHERTU has not been studied in patients with a history of clinically significant cardiac disease or LVEF <50% prior to initiation of treatment. p>
Assess LVEF prior to initiation of ENHERTU and at regular intervals during treatment as clinically indicated. Manage LVEF decrease through treatment interruption. Permanently discontinue ENHERTU if LVEF of <40% or absolute decrease from baseline of>20% is confirmed. When LVEF is >45% and absolute decrease from baseline is 10-20%, continue treatment with ENHERTU. When LVEF is 40-45% and absolute decrease from baseline is <10%, 3 continue treatment with enhertu and repeat lvef assessment within weeks. when is 40-45% absolute decrease from baseline 10-20%, interrupt if has not recovered to 10% baseline, permanently discontinue enhertu. recovers resume at the same dose. or>20%, interrupt ENHERTU and repeat LVEF assessment within 3 weeks. If LVEF of <40% or absolute decrease from baseline of>20% is confirmed, permanently discontinue ENHERTU. Permanently discontinue ENHERTU in patients with symptomatic congestive heart failure. 40%>10%,>40%>
ENHERTU can cause fetal harm when administered to a pregnant woman. Advise patients of the potential risks to a fetus. Verify the pregnancy status of females of reproductive potential prior to the initiation of ENHERTU. Advise females of reproductive potential to use effective contraception during treatment and for at least 7 months following the last dose of ENHERTU. Advise male patients with female partners of reproductive potential to use effective contraception during treatment with ENHERTU and for at least 4 months after the last dose of ENHERTU.
The safety of ENHERTU was evaluated in a pooled analysis of 234 patients with unresectable or metastatic HER2-positive breast cancer who received at least one dose of ENHERTU 5.4 mg/kg in DESTINY- Breast01 and Study DS8201-A-J101. ENHERTU was administered by intravenous infusion once every three weeks. The median duration of treatment was 7 months (range: 0.7 to 31).
Serious adverse reactions occurred in 20% of patients receiving ENHERTU. Serious adverse reactions in >1% of patients who received ENHERTU were interstitial lung disease, pneumonia, vomiting, nausea, cellulitis, hypokalemia, and intestinal obstruction. Fatalities due to adverse reactions occurred in 4.3% of patients including interstitial lung disease (2.6%), and the following events occurred in one patient each (0.4%): acute hepatic failure/acute kidney injury, general physical health deterioration, pneumonia, and hemorrhagic shock.
ENHERTU was permanently discontinued in 9% of patients, of which ILD accounted for 6%. Dose interruptions due to adverse reactions occurred in 33% of patients treated with ENHERTU. The most frequent adverse reactions (>2%) associated with dose interruption were neutropenia, anemia, thrombocytopenia, leukopenia, upper respiratory tract infection, fatigue, nausea, and ILD. Dose reductions occurred in 18% of patients treated with ENHERTU. The most frequent adverse reactions (>2%) associated with dose reduction were fatigue, nausea, and neutropenia.
The most common adverse reactions (frequency ≥20%) were nausea (79%), fatigue (59%), vomiting (47%), alopecia (46%), constipation (35%), decreased appetite (32%), anemia (31%), neutropenia (29%), diarrhea (29%), leukopenia (22%), cough (20%), and thrombocytopenia (20%).
Use in Specific Populations
- Pregnancy: ENHERTU can cause fetal harm when administered to a pregnant woman. Advise patients of the potential risks to a fetus. There are clinical considerations if ENHERTU is used in pregnant women, or if a patient becomes pregnant within 7 months following the last dose of ENHERTU.
- Lactation: There are no data regarding the presence of ENHERTU in human milk, the effects on the breastfed child, or the effects on milk production. Because of the potential for serious adverse reactions in a breastfed child, advise women not to breastfeed during treatment with ENHERTU and for 7 months after the last dose.
- Females and Males of Reproductive Potential: Pregnancy testing: Verify pregnancy status of females of reproductive potential prior to initiation of ENHERTU. Contraception: Females: ENHERTU can cause fetal harm when administered to a pregnant woman. Advise females of reproductive potential to use effective contraception during treatment with ENHERTU and for at least 7 months following the last dose. Males: Advise male patients with female partners of reproductive potential to use effective contraception during treatment with ENHERTU and for at least 4 months following the last dose. Infertility: ENHERTU may impair male reproductive function and fertility.
- Pediatric Use: Safety and effectiveness of ENHERTU have not been established in pediatric patients.
- Geriatric Use: Of the 234 patients with HER2-positive breast cancer treated with ENHERTU 5.4 mg/kg, 26% were ≥65 years and 5% were ≥75 years. No overall differences in efficacy were observed between patients ≥65 years of age compared to younger patients. There was a higher incidence of Grade 3-4 adverse reactions observed in patients aged ≥65 years (53%) as compared to younger patients (42%).
- Hepatic Impairment: In patients with moderate hepatic impairment, due to potentially increased exposure, closely monitor for increased toxicities related to the topoisomerase inhibitor.
To report SUSPECTED ADVERSE REACTIONS, contact Daiichi Sankyo, Inc. at 1-877-437-7763 or FDA at 1-800-FDA-1088 or fda.gov/medwatch.
About Daiichi Sankyo Cancer Enterprise
The mission of Daiichi Sankyo Cancer Enterprise is to leverage our world-class, innovative science and push beyond traditional thinking to create meaningful treatments for patients with cancer. We are dedicated to transforming science into value for patients, and this sense of obligation informs everything we do. Anchored by our DXd antibody drug conjugate (ADC) technology, our powerful research engines include biologics, medicinal chemistry, modality and other research laboratories in Japan, and Plexxikon Inc., our small molecule structure-guided R&D center in Berkeley, CA. For more information, please visit: www.DSCancerEnterprise.com.
About Daiichi Sankyo
Daiichi Sankyo Group is dedicated to the creation and supply of innovative pharmaceutical therapies to improve standards of care and address diversified, unmet medical needs of people globally by leveraging our world-class science and technology. With more than 100 years of scientific expertise and a presence in more than 20 countries, Daiichi Sankyo and its 15,000 employees around the world draw upon a rich legacy of innovation and a robust pipeline of promising new medicines to help people. In addition to a strong portfolio of medicines for cardiovascular diseases, under the Group’s 2025 Vision to become a “Global Pharma Innovator with Competitive Advantage in Oncology,” Daiichi Sankyo is primarily focused on providing novel therapies in oncology, as well as other research areas centered around rare diseases and immune disorders. For more information, please visit: www.daiichisankyo.com.
1 Iqbal N, et al. Mol Biol Int. 2014; 2014: 852748.
2 Bray F et al. CA: Cancer J. Clin 2018;68:394–424.
3 World Cancer Research Fund International. Stomach Cancer Statistics. 2018.
4 American Cancer Society. Tests for Stomach Cancer. 2017.
5 Curea et al. Cancer Biotherapy & Radiopharmaceuticals. 2017;32 (10).
6 NCCN Guidelines® Gastric Cancer. Version 4.2019. December 20, 2019: MS-22-36.
Daiichi Sankyo, Inc.
+1 908 992 6631 (office)
+1 201 709 9309 (mobile)
Daiichi Sankyo, Co., Ltd.
+81 3 6225 1126 (office)
Investor Relations Contact:
About Business Wire
Subscribe to releases from Business Wire
Subscribe to all the latest releases from Business Wire by registering your e-mail address below. You can unsubscribe at any time.
Latest releases from Business Wire
Spirit of Wipro Run Brings Together Thousands of Participants Globally27.9.2020 08:52:00 CEST | Press release
Wipro Limited (NYSE: WIT, BSE: 507685, NSE: WIPRO), a leading global information technology, consulting and business process services company, today organized the 15th edition of the ‘Spirit of Wipro’ (SOW) Run globally with thousands of participants across 35 countries, running separately, yet together in spirit, at a time of their choosing. The theme for this year’s Run was “United. Unstoppable”, which celebrated camaraderie, resilience and a shared sense of community among several thousands of Wipro employees, their friends and families, alumni, customers, partners and suppliers. The SOW Run is an annual, global tradition at Wipro and has been held every year since its inception. This year too, the Run was organized on schedule despite the pandemic induced constraints. The runners strictly adhered to the local COVID-19 guidelines and safety protocols in various countries while participating in the event. Commenting on the Run, Thierry Delaporte, Chief Executive Officer and Managing
BCG Collaborates with Tencent Marketing Insight to Release 2020 BCG x Tencent Digital Luxury Report25.9.2020 12:21:00 CEST | Press release
Since early 2020 when the COVID-19 pandemic broke out worldwide, the luxury market has been hit hard and is expected to decline 25% to 45% compared to the previous year. The Chinese luxury market, however, which has benefitted from successful domestic control of the pandemic and has taken the lead in recovery against a depressed global market environment, is forecast to grow from 20% to 30% in the whole year of 2020. Thanks to its stunning market performance, China has become the main battleground of each major luxury brand. In was in this environment that Boston Consulting Group (BCG) joined hands with Tencent Marketing Insight (TMI) to release the 2020 BCG x Tencent Digital Luxury Report, drawing on deep insights into post COVID-19 trends in the luxury market and consumers based on BCG and TMI’s quantitative consumer research and industry experience, as well as TMI’s marketing and big data capabilities. Crystal Hao, Managing Director & Partner of BCG said, “The luxury market in China
U.S. MRTP Authorization Pathway Explored in PMI’s Latest Scientific Update25.9.2020 12:15:00 CEST | Press release
Philip Morris International (PMI) (NYSE: PM) has released the 11th edition of its Scientific Update, a regularly issued publication on its research efforts to develop and scientifically assess a range of smoke-free alternatives to cigarettes. The latest edition features an overview of the historic decision made by the U.S. Food and Drug Administration (FDA) to authorize the marketing of the IQOS Tobacco Heating System with reduced exposure information. The Scientific Update explains the various MRTP decisions under U.S. law; the steps, processes, and timeline PMI undertook; and the ongoing post-market surveillance and studies that will monitor the impact of the orders on consumer perceptions, behavior, and health. “The FDA undertook a scientific and regulatory evaluation of IQOS and determined that it is ‘appropriate for the promotion of public health’” said Dr. Gizelle Baker, director of Global Scientific Engagement at PMI. “In this edition of our Scientific Update, we describe how th
Palladio Completes $20 Million Series B Financing25.9.2020 12:09:00 CEST | Press release
Palladio Biosciences, Inc. (Palladio), a privately-held, clinical stage biopharmaceutical company developing medicines for orphan diseases of the kidney, announced today the completion of a $20 million Series B investment. The financing was led by new investor, Samsara BioCapital, with participation from new investor, the Roche Venture Fund and existing investors, Medicxi and Osage University Partners. Proceeds from the financing will fund Palladio’s Phase 3 ALERT Study and advance operations. Srinivas Akkaraju M.D, Ph.D, Managing General Partner of Samsara BioCapital, stated, "We are very excited about our investment in Palladio to support the development of lixivaptan, a drug that has the potential to deliver a meaningful therapeutic advancement in the treatment of Autosomal Dominant Polycystic Kidney Disease (ADPKD). The ALERT Study is an important step in assessing the safety differential of lixivaptan.” “We are very pleased that Samsara and the Roche Venture Fund recognize the opp
Ant Group Launches “Trusple,” an AntChain-Powered Global Trade and Financial Services Platform for SMEs and Financial Institutions25.9.2020 09:54:00 CEST | Press release
Ant Group, a leading provider in the development of open platforms for technology-driven inclusive financial services, and the parent company of China’s largest digital payment platform Alipay, today unveiled Trusple, an international trade and financial service platform powered by AntChain, the company’s blockchain-based technology solutions. Trusple aims to make it easier and less costly for all participants – especially Small-to-Medium Enterprises (SMEs) – to sell their products and services to customers around the world. It also reduces costs for financial institutions so they can better serve SMEs in need. This press release features multimedia. View the full release here: https://www.businesswire.com/news/home/20200925005110/en/ (Photo: Business Wire) Based on the concept of “Trust Made Simple,” Trusple works by generating a smart contract once a buyer and a seller upload a trading order on the platform. As the order is executed, the smart contract is automatically updated with k
Ipsen Appoints Philippe Lopes-Fernandes as Executive Vice President, Chief Business Officer25.9.2020 07:00:00 CEST | Press release
Regulatory News: This press release features multimedia. View the full release here: https://www.businesswire.com/news/home/20200924005822/en/ Philippe Lopes-Fernandes, Executive Vice President, Chief Business Officer, Ipsen (Photo: Business Wire) Ipsen (Euronext: IPN; ADR: IPSEY) today announced the appointment of Philippe Lopes-Fernandes as Executive Vice President, Chief Business Officer, effective 1 October 2020. Based in Cambridge, Massachusetts, USA, he will be responsible for business development and alliance management, reporting directly to David Loew, CEO, Ipsen. Philippe will serve on the Executive Leadership Team. “As Chief Business Officer, Philippe will play a crucial role in our external innovation strategy. The ELT and I are delighted to welcome Philippe to Ipsen and look forward to working closely with him. His extensive and impressive track record in international business development, his outstanding reputation and his ability to work closely with the scientific comm
In our pressroom you can read all our latest releases, find our press contacts, images, documents and other relevant information about us.Visit our pressroom