- Submission based on pivotal phase 2 DESTINY-Gastric01 and phase 1 trial data
- Trastuzumab deruxtecan to receive expedited review by Japan MHLW based on SAKIGAKE-designation for second potential indication in Japan
TOKYO, Japan; MUNICH, Gemrany and BASKING RIDGE, NJ, USA I May 7, 2020 – 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.
About HER2
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.8 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
About DESTINY-Gastric01
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.
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.
References:
[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.
SOURCE: Daiichi Sankyo
Post Views: 22
- Submission based on pivotal phase 2 DESTINY-Gastric01 and phase 1 trial data
- Trastuzumab deruxtecan to receive expedited review by Japan MHLW based on SAKIGAKE-designation for second potential indication in Japan
TOKYO, Japan; MUNICH, Gemrany and BASKING RIDGE, NJ, USA I May 7, 2020 – 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.
About HER2
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.8 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
About DESTINY-Gastric01
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.
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.
References:
[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.
SOURCE: Daiichi Sankyo
Post Views: 22
