TOKYO & MUNICH & BASKING RIDGE, N.J.–(BUSINESS WIRE) January 15, 2021 — Daiichi Sankyo Company, Ltd. (hereafter, Daiichi Sankyo) and AstraZeneca’s Enhertu (fam-trastuzumab deruxtecan-nxki) has been approved in the U.S. for the treatment of adult patients with locally advanced or metastatic HER2 positive gastric or gastroesophageal junction (GEJ) adenocarcinoma who have received a prior trastuzumab-based regimen.
In the U.S., gastric cancer is more frequently diagnosed in the advanced stage, with only approximately 5% of patients surviving five years.1,2 Approximately one in five gastric cancers are HER2 positive.3
“Patients with metastatic HER2 positive gastric cancer with progression following first-line treatment have historically faced poor outcomes, including low response to treatment and rapid disease progression,” said Ronan Kelly, MD, MBA, Director of the Charles A. Sammons Cancer Center and the W.W. Caruth, Jr. Chair of Immunology at Baylor University Medical Center, Dallas, Texas. “This approval represents the first time a HER2 directed medicine has demonstrated a significant improvement in survival compared to chemotherapy for patients following initial treatment in the metastatic setting and it has the potential to become the new standard of care for this patient population.”
Regular approval by the U.S. Food and Drug Administration (FDA) was based on the positive results from the randomized pivotal DESTINY-Gastric01 phase 2 trial, in which Enhertu demonstrated a statistically significant and clinically meaningful improvement in overall survival (OS) and objective response rate (ORR) versus chemotherapy (irinotecan or paclitaxel) in patients with advanced gastric or GEJ adenocarcinoma who had progressed on at least two prior regimens including trastuzumab, a fluoropyrimidine and a platinum-containing chemotherapy. Enhertu is approved with Boxed WARNINGS for interstitial lung disease (ILD)/pneumonitis and embryo-fetal toxicityEnhertu
In the DESTINY-Gastric01 trial, patients (n=126) in the Enhertu treatment arm had a 41% reduction in the risk of death versus patients (n=62) treated with chemotherapy (based on a hazard ratio [HR] of 0.59; 95% confidence interval [CI] 0.39-0.88; p=0.0097) at a pre-specified interim analysis with a median OS of 12.5 months [95% CI 9.6-14.3] versus 8.4 months [95% CI 6.9-10.7] with chemotherapy.
Confirmed ORR, assessed by independent central review, was a major efficacy outcome. Results showed a confirmed ORR of 40.5% [95% CI 31.8-49.6] with Enhertu compared to 11.3% [95% CI 4.7-21.9] with chemotherapy. Patients treated with Enhertu had a 7.9% complete response rate (n=10) and a 32.5% partial response rate (n=41) compared to a complete response rate of 0% (n=0) and a partial response rate of 11.3% (n=7) for patients treated with chemotherapy. Additionally, Enhertu showed a median duration of response (DoR) of 11.3 months [95% CI 5.6-NR] versus 3.9 months [95% CI 3.0-4.9] with chemotherapy.
Enhertu also demonstrated a median progression-free survival (PFS) of 5.6 months [95% CI 4.3-6.9] compared to 3.5 months [95% CI 2.0-4.3] (HR=0.47; 95% CI 0.31-0.71) with chemotherapy.
Results from the DESTINY-Gastric01 trial were presented at the 2020 American Society of Clinical Oncology (ASCO) meeting and published in The New England Journal of Medicine.4
Enhertu is approved with Boxed WARNINGS for interstitial lung disease (ILD)/pneumonitis and embryo-fetal toxicity. The safety of Enhertu was evaluated in 187 patients with locally advanced or metastatic HER2 positive gastric or GEJ adenocarcinoma in DESTINY-Gastric01. The most common adverse reactions (≥20%), including laboratory abnormalities, were hemoglobin decreased, white blood cell count decreased, neutrophil count decreased, lymphocyte count decreased, platelet count decreased, nausea, decreased appetite, anemia, aspartate aminotransferase increased, fatigue, blood alkaline phosphatase increased, alanine aminotransferase increased, diarrhea, hypokalemia, vomiting, constipation, blood bilirubin increased, pyrexia, and alopecia. In DESTINY-Gastric01, of the 125 patients with locally advanced or metastatic HER2 positive gastric or GEJ adenocarcinoma treated with Enhertu 6.4 mg/kg, interstitial lung disease occurred in 10% of patients. Median time to first onset of ILD was 2.8 months (range: 1.2 to 21.0).
“Enhertu is the first antibody drug conjugate to receive approval in the U.S. for the treatment of patients with metastatic gastric cancer, and represents a major advance in managing this difficult-to-treat disease,” said Antoine Yver, MD, MSc, Executive Vice President and Global Head, Oncology Research and Development, Daiichi Sankyo. “This second indication in the U.S. represents an important step forward in our ambitious plan to accelerate the development of Enhertu across a broad range of HER2 targetable cancers.”
“Today’s approval of Enhertu represents the first HER2 directed medicine approved in a decade for patients with HER2 positive metastatic gastric cancer,” said Dave Fredrickson, Executive Vice President, Oncology Business Unit, AstraZeneca. “The results from the DESTINY-Gastric01 trial highlight the potential to change clinical practice, showing a forty-one percent improvement in survival and a response rate more than three times higher with Enhertu compared to chemotherapy. We are thrilled to bring this important medicine to more patients and physicians in the U.S.”
This is the second regulatory approval for Enhertu in the U.S. Enhertu is also approved in the U.S. under accelerated approval, and in Japan, under the conditional early approval system, 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 based on the DESTINY-Breast01 trial. Enhertu is also approved in Japan for HER2 positive unresectable advanced or recurrent gastric cancer that has progressed after chemotherapy based on the DESTINY-Gastric01 trial.
Enhertu previously received Priority Review and Breakthrough Therapy Designation (BTD) in the U.S. for the treatment of patients with previously treated HER2 positive metastatic gastric cancer, as well as Orphan Drug Designation (ODD) for patients with gastric cancer, including gastroesophageal junction cancer. Two additional phase 2 trials, DESTINY-Gastric02 and DESTINY-Gastric03, are underway, further evaluating the use of Enhertu in patients with HER2 positive metastatic gastric cancer.
Daiichi Sankyo and AstraZeneca are committed to ensuring that patients in the U.S. who are prescribed Enhertu can access the medication and receive necessary financial support. Provider and patient support, reimbursement and distribution for Enhertu in the U.S. will be accessible by visiting www.ENHERTU4U.com or calling 1-833-ENHERTU (1-833-364-3788).
Please visit www.ENHERTU.com for full Prescribing Information, including Boxed WARNINGS, and Medication Guide.
About Gastric Cancer
Gastric (stomach) cancer is the fifth most common cancer worldwide and the third leading cause of cancer mortality with a five-year survival rate of 5% for metastatic disease; there were approximately one million new cases reported in 2020 and more than 768,000 deaths.2,5 In the U.S., it is estimated that 27,600 new cases of gastric cancer were diagnosed in 2020 and more than 11,000 people died from the disease.6
Approximately one in five gastric cancers are HER2 positive.3 HER2 is a tyrosine kinase receptor growth-promoting protein expressed on the surface of many types of tumors including breast, gastric, lung and colorectal cancer. Gastric cancer is usually diagnosed in the advanced stage, but even when diagnosed in earlier stages of the disease, the survival rate remains modest.1 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 survival outcomes when added to chemotherapy. For patients with metastatic gastric cancer that progresses following initial treatment with a trastuzumab-based regimen, there were previously no other approved HER2 targeted medicines prior to the approval of Enhertu.3
DESTINY-Gastric01 is an open-label, multi-center, randomized, pivotal phase 2 trial evaluating the safety and efficacy of ENHERTU (6.4 mg/kg) versus investigator’s choice of chemotherapy in a primary cohort of 188 patients from Japan and South Korea with HER2 positive (defined as IHC3+ or IHC2+/ISH+), advanced gastric or GEJ adenocarcinoma who had progressed on two or more prior treatment regimens including trastuzumab, a fluoropyrimidine and platinum-containing chemotherapy. Patients were randomized 2:1 to receive Enhertu or investigator’s choice of chemotherapy (paclitaxel or irinotecan monotherapy). Patients were treated with Enhertu 6.4mg/kg once every three weeks or chemotherapy.
The main efficacy outcome measures were ORR assessed by independent central review according to RECIST v1.1 and OS in the intent-to-treat population. Additional efficacy outcome measures were PFS and DoR.
Enhertu (trastuzumab deruxtecan; fam-trastuzumab deruxtecan-nxki in the U.S.) is a HER2 directed antibody drug conjugate (ADC). Designed using Daiichi Sankyo’s proprietary DXd ADC technology, Enhertu 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. Enhertu is comprised of a humanized anti-HER2 IgG1 monoclonal antibody with the same amino acid sequence as trastuzumab attached to a topoisomerase I inhibitor payload, an exatecan derivative, via a tetrapeptide-based cleavable linker.
Enhertu (5.4 mg/kg) is approved in the U.S. under accelerated approval, and in Japan, under the conditional early approval system, 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 based on the DESTINY-Breast01 trial, and received a CHMP positive opinion in December 2020 as monotherapy 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. Enhertu (6.4 mg/kg) is also approved in the U.S. and Japan for the treatment of previously treated patients with HER2 positive metastatic gastric cancer based on the DESTINY-Gastric01 trial.
About the Enhertu Clinical Development Program
A comprehensive development program is underway globally with nine pivotal trials evaluating the efficacy and safety of ENHERTU monotherapy across multiple HER2 targetable cancers including breast, gastric and lung cancers. Trials in combination with other anticancer treatments, such as immunotherapy, are also underway.
In May 2020, Enhertu received BTD in the U.S. for the treatment of patients with metastatic non-small cell lung cancer whose tumors have a HER2 mutation and with disease progression on or after platinum-based therapy.
In March 2020, the European Medicines Agency’s CHMP granted Enhertu accelerated assessment for the treatment of adults with unresectable or metastatic HER2 positive breast cancer who have received two or more prior anti-HER2 based regimens.
About the Collaboration between Daiichi Sankyo and AstraZeneca
Daiichi Sankyo and AstraZeneca entered into a global collaboration to jointly develop and commercialize Enhertu (a HER2 directed ADC) in March 2019, and datopotamab deruxtecan (Dato-DXd; DS-1062; a TROP2 directed ADC) in July 2020, except in Japan where Daiichi Sankyo maintains exclusive rights. Daiichi Sankyo is responsible for manufacturing and supply of Enhertu and datopotamab deruxtecan.
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.
- Locally advanced or metastatic HER2-positive gastric or gastroesophageal junction adenocarcinoma who have received a prior trastuzumab-based regimen.
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.
ENHERTU® is a registered trademark of Daiichi Sankyo Company, Ltd.
- 1 Curea F.G, et al. Cancer Biotherapy & Radiopharmaceuticals. 2017;32 (10).
2 American Cancer Society. Stomach Cancer: Stomach Cancer Survival Rates. October 2020.
3 American Cancer Society. Targeted Therapies for Stomach Cancer. October 2020.
4 Shitara, K et al. N Engl J Med. 2020;382(25):2419-2430.
5 Global Cancer Observatory. World. Accessed January 2021.
6 National Cancer Institute. Cancer Stat Facts: Stomach Cancer. Accessed January 2021.
Source: Daiichi Sankyo
Posted: January 2021
Enhertu (fam-trastuzumab deruxtecan-nxki) FDA Approval History