TOKYO & MUNICH--(BUSINESS WIRE)--Daiichi Sankyo (TSE: 4568) and AstraZeneca’s (LSE/STO/Nasdaq: AZN) ENHERTU® (trastuzumab deruxtecan) has been recommended for support successful the European Union (EU) arsenic a monotherapy for the attraction of big patients with precocious HER2 affirmative gastric oregon gastroesophageal junction (GEJ) adenocarcinoma who person received a anterior trastuzumab-based regimen.
ENHERTU is simply a specifically engineered HER2 directed antibody cause conjugate (ADC) being jointly developed and commercialized by Daiichi Sankyo and AstraZeneca.
The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) based its affirmative sentiment connected results from the DESTINY-Gastric02 and the DESTINY-Gastric01 signifier 2 trials.
In DESTINY-Gastric02, conducted successful patients from North America and Europe, updated results showed attraction with ENHERTU resulted successful a confirmed nonsubjective effect complaint (ORR) of 41.8% (95% assurance interval [CI]: 30.8-53.4) arsenic assessed by autarkic cardinal reappraisal (ICR). Median duration of effect (DoR) was 8.1 months (95% CI: 5.9-NE). Median wide endurance (OS) was 12.1 months (95% CI: 9.4-15.4). Primary results from the DESTINY-Gastric02 signifier 2 proceedings were presented astatine the 2021 European Society for Medical Oncology (ESMO) Congress with updated information presented astatine ESMO 2022.
In DESTINY-Gastric01, conducted successful patients from Japan and South Korea, attraction with ENHERTU resulted successful an ORR of 51.3% (95% CI: 41.9-60.5) versus 14.3% (95% CI: 6.4-26.2) with chemotherapy (irinotecan oregon paclitaxel) arsenic assessed by ICR (p<0.0001). Confirmed ORR, a large efficacy outcome, was 42.0% (95% CI: 33.0-51.4) with ENHERTU versus 12.5% (95% CI: 5.2-24.1) with chemotherapy arsenic assessed by ICR. Patients treated with ENHERTU besides had a 40% simplification successful the hazard of decease versus patients treated with chemotherapy (hazard ratio [HR] = 0.60; 95% CI: 0.42-0.86, p=0.01) with a median OS of 12.5 months (95% CI: 10.3-15.2) versus 8.9 months (95% CI: 6.4-10.4). The superior investigation was published in The New England Journal of Medicine, with updated information presented astatine the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting.
The proposal volition present beryllium reviewed by the European Commission, which has the authorization to assistance selling authorizations for medicines successful the EU.
“ENHERTU is the archetypal HER2 directed medicine to show a important betterment successful wide endurance compared to chemotherapy successful patients with gastric crab pursuing archetypal attraction with a HER2 directed medicine successful the precocious oregon metastatic setting,” said Ken Takeshita, MD, Global Head, R&D, Daiichi Sankyo. “The CHMP sentiment recognizes the precocious unmet request successful this diligent colonisation and brings america 1 measurement person to bringing this medicine to patients with gastric crab successful Europe.”
“Gastric crab is usually diagnosed successful the precocious signifier successful galore European countries and patients look precocious mortality rates,” said Susan Galbraith, MBBCh, PhD, Executive Vice President, Oncology R&D, AstraZeneca. “If approved, ENHERTU would beryllium the archetypal HER2 directed medicine for patients with precocious gastric crab successful the European Union successful much than a decade.”
In DESTINY-Gastric02, the information illustration observed with patients treated with ENHERTU was accordant with that seen successful different trials of ENHERTU with nary caller information signals identified. Grade 3 oregon higher treatment-emergent adverse events (TEAEs) occurred successful 55.7% of patients receiving ENHERTU 6.4 mg/kg. The astir communal people 3 oregon higher treatment-related TEAEs occurring successful ≥10% of patients receiving ENHERTU was anemia (13.9%). There were 8 cases (10.1%) of treatment-related interstitial lung illness (ILD) oregon pneumonitis arsenic determined by an autarkic adjudication committee. The bulk (six) were debased people (grade 1 oregon 2), with 2 people 5 ILD oregon pneumonitis events reported.
In DESTINY-Gastric01, the information illustration observed successful patients treated with ENHERTU was accordant with that seen successful different trials of ENHERTU with nary caller information signals identified. Grade 3 oregon higher TEAEs occurred successful 85.6% of patients receiving ENHERTU 6.4 mg/kg. The astir communal people 3 oregon higher treatment-related TEAEs occurring successful ≥20% of patients receiving ENHERTU were decreased neutrophil number (51.2%), anemia (38.4%) and decreased achromatic humor compartment number (20.8%). There were 16 cases (12.8%) of treatment-related ILD oregon pneumonitis arsenic determined by an autarkic adjudication committee. The bulk (13) were debased people (grade 1 oregon 2), with 2 people 3 events and 1 people 4 lawsuit reported. No people 5 ILD oregon pneumonitis events occurred.
ENHERTU is not presently approved successful the EU for the attraction of precocious gastric crab and is taxable to further monitoring.
About DESTINY-Gastric02
DESTINY-Gastric02 is an open-label, single-arm signifier 2 proceedings successful Western patients evaluating the efficacy and information of ENHERTU (6.4 mg/kg) successful patients with HER2 affirmative metastatic and/or unresectable gastric oregon GEJ adenocarcinoma with illness progression connected oregon aft a trastuzumab-containing regimen.
The superior endpoint of DESTINY-Gastric02 is confirmed ORR based connected ICR. Secondary endpoints see progression-free endurance (PFS), OS, DoR and safety.
DESTINY-Gastric02 enrolled 79 patients astatine aggregate sites successful North America and Europe. For much accusation astir the trial, sojourn ClinicalTrials.gov.
About DESTINY-Gastric01
DESTINY-Gastric01 is simply a randomized, open-label signifier 2 proceedings evaluating the efficacy and information of ENHERTU (6.4 mg/kg) successful patients from Japan and South Korea with chiefly HER2 affirmative (defined arsenic immunohistochemistry (IHC) 3+ oregon IHC 2+/in-situ hybridization (ISH)+) precocious gastric crab oregon GEJ adenocarcinoma whose tumors person progressed connected 2 oregon much anterior attraction regimens including fluoropyrimidine (5-FU), platinum chemotherapy and trastuzumab. Patients were randomized 2:1 to person ENHERTU oregon physician’s prime of chemotherapy (paclitaxel oregon irinotecan monotherapy).
The superior endpoint of DESTINY-Gastric01 is ORR. Secondary endpoints see OS, PFS, DoR, illness power complaint and clip to attraction failure, arsenic good arsenic pharmacokinetic and information endpoints.
DESTINY-Gastric01 enrolled 187 patients astatine aggregate sites successful Japan and South Korea. For much accusation astir the trial, sojourn ClinicalTrials.gov.
About HER2 Positive Gastric Cancer
Gastric (stomach) crab is the 5th astir communal crab worldwide and the 4th highest starring origin of crab mortality, with a five-year planetary endurance complaint of 5% to 10% for precocious oregon metastatic disease.1,2,3 Approximately 1 cardinal caller patients were diagnosed with gastric crab successful 2020, with 768,000 deaths reported globally.4 In Europe, astir 136,000 cases of gastric crab are diagnosed annually, and Eastern Europe has the 2nd highest incidence of gastric crab worldwide aft Eastern Asia.3,4 Gastric crab is the sixth starring origin of crab decease successful Europe and is typically diagnosed successful the precocious stage. Even erstwhile diagnosed successful earlier stages of the disease, the endurance complaint remains modest.2,5,6
Approximately 1 successful 5 gastric cancers are HER2 positive.7,8 HER2 is simply a tyrosine kinase receptor maturation promoting macromolecule expressed connected the aboveground of galore types of tumors including breast, gastric, lung and colorectal cancers.7 HER2 overexpression whitethorn beryllium associated with a circumstantial HER2 cistron alteration known arsenic HER2 amplification.8
Recommended first-line attraction for HER2 affirmative precocious oregon metastatic gastric crab is operation chemotherapy positive trastuzumab, an anti-HER2 medicine, which has been shown to amended endurance outcomes erstwhile added to chemotherapy.9,10 For patients with metastatic gastric crab that progresses pursuing archetypal attraction with a trastuzumab-based regimen, attraction options are limited, and successful galore regions of the satellite determination are nary further HER2 directed medicines available.1,11,12
About ENHERTU
ENHERTU (trastuzumab deruxtecan; fam-trastuzumab deruxtecan-nxki successful the U.S. only) is a HER2 directed ADC. Designed utilizing Daiichi Sankyo’s proprietary DXd ADC technology, ENHERTU is the pb ADC successful the oncology portfolio of Daiichi Sankyo and the astir precocious programme successful AstraZeneca’s ADC technological platform. ENHERTU consists of a HER2 monoclonal antibody attached to a topoisomerase I inhibitor payload, an exatecan derivative, via a unchangeable tetrapeptide-based cleavable linker.
ENHERTU (5.4 mg/kg) is approved successful much than 35 countries for the attraction of big patients with unresectable oregon metastatic HER2 affirmative bosom crab who person received a (or 1 oregon more) anterior anti-HER2-based regimen, either successful the metastatic mounting oregon successful the neoadjuvant oregon adjuvant setting, and person developed illness recurrence during oregon wrong six months of completing therapy based connected the results from the DESTINY-Breast03 trial. ENHERTU besides is approved successful respective countries for the attraction of big patients with unresectable oregon metastatic HER2 affirmative bosom crab who person received 2 oregon much anterior anti-HER2-based regimens based connected the results from the DESTINY-Breast01 trial.
ENHERTU (5.4 mg/kg) is approved successful Brazil and the U.S. for the attraction of big patients with unresectable oregon metastatic HER2 debased (IHC 1+ oregon IHC 2+/ISH-) bosom crab who person received a anterior chemotherapy successful the metastatic mounting oregon developed illness recurrence during oregon wrong six months of completing adjuvant chemotherapy based connected the results from the DESTINY-Breast04 trial.
ENHERTU (5.4 mg/kg) is approved nether accelerated support successful the U.S. for the attraction of big patients with unresectable oregon metastatic non-small compartment lung crab (NSCLC) whose tumors person activating HER2 (ERBB2) mutations, arsenic detected by an FDA-approved test, and who person received a anterior systemic therapy based connected the results of the DESTINY-Lung02 trial. Continued support for this denotation whitethorn beryllium contingent upon verification and statement of objective payment successful a confirmatory trial.
ENHERTU (6.4 mg/kg) is approved successful respective countries for the attraction of big patients with locally precocious oregon metastatic HER2 affirmative gastric oregon gastroesophageal junction (GEJ) adenocarcinoma who person received a anterior trastuzumab-based regimen based connected the results from the DESTINY-Gastric01 trial.
About the ENHERTU Clinical Development Program
A broad planetary improvement programme is underway evaluating the efficacy and information of ENHERTU monotherapy crossed aggregate HER2 targetable cancers including breast, gastric, lung and colorectal cancers. Trials successful operation with different anticancer treatments, specified arsenic immunotherapy, are besides underway.
Regulatory applications for ENHERTU successful bosom and gastric crab are presently nether reappraisal successful respective countries based connected the DESTINY-Breast01, DESTINY-Breast03, DESTINY-Breast04, DESTINY-Gastric01 and DESTINY-Gastric02 trials, respectively.
About the Daiichi Sankyo and AstraZeneca Collaboration
Daiichi Sankyo and AstraZeneca entered into a planetary collaboration to jointly make and commercialize ENHERTU successful March 2019 and datopotamab deruxtecan (Dato-DXd) successful July 2020, but successful Japan wherever Daiichi Sankyo maintains exclusive rights for each ADC. Daiichi Sankyo is liable for the manufacturing and proviso of ENHERTU and datopotamab deruxtecan.
About Daiichi Sankyo
Daiichi Sankyo is dedicated to creating caller modalities and innovative medicines by leveraging our world-class subject and exertion for our intent “to lend to the enrichment of prime of beingness astir the world.” In summation to our existent portfolio of medicines for crab and cardiovascular disease, Daiichi Sankyo is chiefly focused connected processing caller therapies for radical with crab arsenic good arsenic different diseases with precocious unmet aesculapian needs. With much than 100 years of technological expertise and a beingness successful much than 20 countries, Daiichi Sankyo and its 16,000 employees astir the satellite gully upon a affluent bequest of innovation to recognize our 2030 Vision to go an “Innovative Global Healthcare Company Contributing to the Sustainable Development of Society.” For much information, delight sojourn www.daiichisankyo.com.
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References
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2 SEER Cancer Stat Facts: Stomach Cancer 2012-2018. Accessed November 2022.
3 Sung H, et al. Ca Cancer J Clin. 2021;71:209–249.
4 WHO. Stomach Cancer Fact Sheet. Accessed November 2022.
5 WHO. Cancer Today Europe Mortality. Accessed November 2022
6 Cancer Research UK. Stomach Cancer Survival Statistics. Accessed November 2022.
7 Iqbal N, et al. Mol Biol Int. 2014;2014:852748.
8 Abrahao-Machado LF, et al. World J Gastroenterol. 2016;22(19):4619-4625.
9 Oditura M, et al. World J Gastroenterol. 2014 Feb 21;20(7):1635-49.
10 Lordick F, et al. Annals of Oncology. 2022; 33(10):1012.
11 Thuss-Patience PC, et al. Lancet Oncol. 2017;18(5):640-653.
12 Satoh T, et al. J Clin Oncol. 2014;32(19):2039‐2049.
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