DESTINY-Gastric05 Phase 3 Trial of ENHERTU® Initiated in Patients with Previously Untreated HER2 Positive Advanced Gastric Cancer
DESTINY-Gastric05, a new phase 3 trial, has commenced with the first patient dosed to evaluate ENHERTU® (trastuzumab deruxtecan) in combination therapy for previously untreated HER2 positive advanced gastric cancer. The study will test ENHERTU with fluoropyrimidine chemotherapy and KEYTRUDA® versus the current standard treatment.
The trial focuses on patients with unresectable, locally advanced or metastatic HER2 positive gastric or gastroesophageal junction cancer with PD-L1 CPS ≥1. An exploratory cohort with PD-L1 CPS <1 will also be included. This initiative follows positive survival results from DESTINY-Gastric04 in second-line treatment.
ENHERTU, a HER2 directed DXd antibody drug conjugate jointly developed by Daiichi Sankyo and AstraZeneca, is currently approved in over 65 countries for second-line or third-line metastatic HER2 positive gastric cancer treatment.
DESTINY-Gastric05, un nuovo studio di fase 3, è iniziato con il primo paziente trattato per valutare ENHERTU® (trastuzumab deruxtecan) in terapia combinata per il carcinoma gastrico avanzato HER2 positivo precedentemente non trattato. Lo studio testerà ENHERTU con chemioterapia fluoropirimidinica e KEYTRUDA® rispetto al trattamento standard attuale.
La sperimentazione si concentra su pazienti con carcinoma gastrico o della giunzione gastroesofagea HER2 positivo, localmente avanzato o metastatico, non resecabile, con PD-L1 CPS ≥1. Sarà inclusa anche una coorte esplorativa con PD-L1 CPS <1. Questa iniziativa segue risultati positivi di sopravvivenza dallo studio DESTINY-Gastric04 nel trattamento di seconda linea.
ENHERTU, un coniugato farmaco anticorpo DXd diretto contro HER2, sviluppato congiuntamente da Daiichi Sankyo e AstraZeneca, è attualmente approvato in oltre 65 paesi per il trattamento del carcinoma gastrico metastatico HER2 positivo in seconda o terza linea.
DESTINY-Gastric05, un nuevo ensayo de fase 3, ha comenzado con el primer paciente tratado para evaluar ENHERTU® (trastuzumab deruxtecan) en terapia combinada para el cáncer gástrico avanzado HER2 positivo previamente no tratado. El estudio probará ENHERTU con quimioterapia fluoropirimidina y KEYTRUDA® en comparación con el tratamiento estándar actual.
El ensayo se centra en pacientes con cáncer gástrico o de la unión gastroesofágica HER2 positivo, localmente avanzado o metastásico, irresecable, con PD-L1 CPS ≥1. También se incluirá una cohorte exploratoria con PD-L1 CPS <1. Esta iniciativa sigue a los resultados positivos de supervivencia del DESTINY-Gastric04 en el tratamiento de segunda línea.
ENHERTU, un conjugado de fármaco anticuerpo DXd dirigido a HER2, desarrollado conjuntamente por Daiichi Sankyo y AstraZeneca, está actualmente aprobado en más de 65 países para el tratamiento del cáncer gástrico metastásico HER2 positivo en segunda o tercera línea.
DESTINY-Gastric05, 새로운 3상 시험이 시작되었으며, 첫 번째 환자가 ENHERTU® (트라스투주맙 데룩스테칸)를 평가하기 위해 투여되었습니다. 이 시험은 이전에 치료받지 않은 HER2 양성 진행성 위암에 대한 병합 요법을 평가합니다. 연구는 ENHERTU와 플루오로피리미딘 화학요법 및 KEYTRUDA®를 현재 표준 치료와 비교합니다.
시험은 PD-L1 CPS ≥1인 절제 불가능한, 국소 진행성 또는 전이성 HER2 양성 위암 또는 위식도 접합암 환자에 초점을 맞춥니다. PD-L1 CPS <1인 탐색적 집단도 포함될 것입니다. 이 이니셔티브는 두 번째 치료에서 DESTINY-Gastric04의 긍정적인 생존 결과를 따릅니다.
ENHERTU는 Daiichi Sankyo와 AstraZeneca가 공동 개발한 HER2 표적 DXd 항체 약물 접합체로, 현재 65개국 이상에서 HER2 양성 전이성 위암 치료를 위한 2차 또는 3차 치료로 승인되었습니다.
DESTINY-Gastric05, un nouvel essai de phase 3, a commencé avec le premier patient traité pour évaluer ENHERTU® (trastuzumab deruxtecan) dans le cadre d'une thérapie combinée pour le cancer gastrique avancé HER2 positif précédemment non traité. L'étude testera ENHERTU avec une chimiothérapie fluoropyrimidine et KEYTRUDA® par rapport au traitement standard actuel.
L'essai se concentre sur les patients atteints de cancer gastrique ou de la jonction gastro-œsophagienne HER2 positif, localement avancé ou métastatique, non résécable, avec un PD-L1 CPS ≥1. Un groupe exploratoire avec PD-L1 CPS <1 sera également inclus. Cette initiative fait suite à des résultats de survie positifs de DESTINY-Gastric04 dans le traitement de deuxième ligne.
ENHERTU, un conjugué d'anticorps DXd dirigé contre HER2, développé conjointement par Daiichi Sankyo et AstraZeneca, est actuellement approuvé dans plus de 65 pays pour le traitement du cancer gastrique métastatique HER2 positif en deuxième ou troisième ligne.
DESTINY-Gastric05, eine neue Phase-3-Studie, hat begonnen, und der erste Patient wurde behandelt, um ENHERTU® (Trastuzumab Deruxtecan) in einer Kombinationstherapie für zuvor unbehandelten HER2-positiven fortgeschrittenen Magenkrebs zu bewerten. Die Studie wird ENHERTU mit fluoropyrimidinhaltiger Chemotherapie und KEYTRUDA® im Vergleich zur aktuellen Standardbehandlung testen.
Die Studie konzentriert sich auf Patienten mit nicht resektablem, lokal fortgeschrittenem oder metastasiertem HER2-positivem Magen- oder gastroösophagealen Übergangskrebs mit PD-L1 CPS ≥1. Eine explorative Kohorte mit PD-L1 CPS <1 wird ebenfalls einbezogen. Diese Initiative folgt auf positive Überlebensdaten aus DESTINY-Gastric04 in der Zweitlinientherapie.
ENHERTU, ein HER2-gerichteter DXd-Antikörper-Wirkstoff-Konjugat, das gemeinsam von Daiichi Sankyo und AstraZeneca entwickelt wurde, ist derzeit in über 65 Ländern für die Zweit- oder Drittlinientherapie von HER2-positivem metastasiertem Magenkrebs zugelassen.
- Expansion into first-line treatment following positive survival results in second-line setting
- Potential for a new platinum-free treatment option in first-line therapy
- Large existing market presence with approvals in over 65 countries
- Gastric cancer's poor prognosis with 5-10% five-year survival rate in advanced stages
Insights
The initiation of the DESTINY-Gastric05 Phase 3 trial marks a significant advancement in the treatment landscape for HER2 positive gastric cancer. What's clinically meaningful here is the potential shift of ENHERTU from later-line therapy to the first-line setting, where treatment decisions have the greatest impact on patient outcomes.
This trial specifically evaluates a platinum-free regimen, which addresses an important clinical need. Current standard first-line treatment includes platinum-based chemotherapy, which while effective, carries substantial toxicity. The exploration of ENHERTU with fluoropyrimidine and pembrolizumab aims to maintain or improve efficacy while potentially reducing the toxicity burden for patients.
The trial design reflects sophisticated clinical thinking by incorporating PD-L1 stratification (CPS ≥1 and <1), acknowledging the heterogeneity of gastric cancer and importance of biomarker-guided treatment. Importantly, this builds upon demonstrated efficacy in the second-line setting from DESTINY-Gastric04, suggesting a logical extension of the drug's application.
Gastric cancer remains a devastating diagnosis with 5-10% five-year survival in advanced stages. If successful, this approach could establish a new paradigm in first-line treatment for these patients, addressing a substantial unmet medical need in a cancer that has seen therapeutic innovation.
The progression of ENHERTU into first-line gastric cancer treatment represents a strategic expansion of this cornerstone therapy in AstraZeneca's oncology portfolio. Moving from second/third-line to first-line positioning is the golden pathway in oncology drug development, substantially expanding the addressable patient population and potential duration of therapy.
ENHERTU has already established itself as a successful commercial product across multiple tumor types. Its current approval in over 65 countries for later-line gastric cancer treatment provides an established foundation for this expansion effort. First-line approval would significantly increase market penetration as all eligible newly-diagnosed patients would become candidates for therapy, rather than only those who progress on initial treatments.
The continued collaboration with Daiichi Sankyo demonstrates the value both companies see in ENHERTU's potential. The addition of Merck's pembrolizumab to the regimen further validates the combination approach and reflects ongoing industry trends toward multi-modality treatment strategies.
For investors, this trial initiation signals continued investment in expanding ENHERTU's utility across the treatment continuum in gastric cancer. While results are still years away, the advancement into first-line therapy testing represents a logical progression that could meaningfully contribute to ENHERTU's long-term commercial potential in this difficult-to-treat cancer with effective options.
ENHERTU is a specifically engineered HER2 directed DXd antibody drug conjugate (ADC) discovered by Daiichi Sankyo (TSE: 4568) and being jointly developed and commercialized by Daiichi Sankyo and AstraZeneca (LSE/STO/Nasdaq: AZN).
Gastric cancer is associated with a poor prognosis, particularly in advanced stages of the disease where the five-year survival rate is
“Following the positive overall survival results seen with DESTINY-Gastric04 in the second-line HER2 positive metastatic gastric cancer setting, the DESTINY-Gastric05 trial will explore the role of ENHERTU earlier in the metastatic setting as a first-line treatment,” said Mark Rutstein, MD, Global Head, Oncology Clinical Development, Daiichi Sankyo. “With DESTINY-Gastric05, we are evaluating whether a potential platinum-free chemotherapy regimen of ENHERTU combined with immunotherapy and a fluoropyrimidine chemotherapy can further improve survival in patients with previously untreated HER2 positive metastatic gastric cancer.”
ENHERTU is currently approved in more than 65 countries in the second-line or third-line metastatic setting of HER2 positive gastric cancer based on DESTINY-Gastric01, a randomized phase 2 trial, and DESTINY-Gastric02 and DESTINY-Gastric06, two single-arm phase 2 trials.
KEYTRUDA® is a registered trademark of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc.,
About DESTINY-Gastric05
DESTINY-Gastric05 is a global, multicenter, randomized, open-label, phase 3 trial evaluating the efficacy and safety of ENHERTU (5.4 mg/kg) in combination with a fluoropyrimidine-based chemotherapy (5-FU or capecitabine) and Merck’s (known as MSD outside of the US and
The primary endpoint is progression-free survival (PFS) as assessed by blinded independent central review. The key secondary endpoint is overall survival. Additional secondary endpoints include PFS as assessed by investigator, objective response rate, duration of response and safety.
An exploratory cohort of 150 patients with PD-L1 CPS <1 will be randomized to either ENHERTU plus fluoropyrimidine (5-FU or capecitabine) or trastuzumab plus platinum-based chemotherapy (cisplatin plus 5-FU or oxaliplatin plus capecitabine).
DESTINY-Gastric05 will enroll patients across multiple sites in
About HER2 Positive Gastric Cancer
Gastric (stomach) cancer is the fifth most common cancer worldwide and the fifth leading cause of cancer-related death.4 Approximately one million cases were diagnosed in 2022.4 Gastric cancer is associated with a poor prognosis, particularly in advanced stages of the disease where the five-year survival rate is
HER2 is a tyrosine kinase receptor growth-promoting protein expressed on the surface of many types of tumors, including gastric cancer.5 Approximately one in five gastric cancers globally are HER2 positive.5,6
Recommended first-line treatment for HER2 positive advanced gastric cancer with PD-L1 CPS ≥1 is trastuzumab in combination with platinum-based chemotherapy (cisplatin plus 5-FU or oxaliplatin plus capecitabine) and pembrolizumab.2,3 In patients with PD-L1 CPS <1 recommended first-line treatment is trastuzumab plus platinum-based chemotherapy (cisplatin plus 5-FU or oxaliplatin plus capecitabine).2 New treatment strategies, including additional HER2 directed treatment options, are needed to continue to improve survival in patients with previously untreated advanced gastric cancer.
About ENHERTU
ENHERTU (trastuzumab deruxtecan; fam-trastuzumab deruxtecan-nxki in the
ENHERTU (5.4 mg/kg) is approved in more than 75 countries worldwide for the treatment of adult patients with unresectable or metastatic HER2 positive (immunohistochemistry [IHC] 3+ or in-situ hybridization (ISH)+) breast cancer who have received a prior anti-HER2-based regimen, either in the metastatic setting or in the neoadjuvant or adjuvant setting, and have developed disease recurrence during or within six months of completing therapy based on the results from the DESTINY-Breast03 trial.
ENHERTU (5.4 mg/kg) is approved in more than 75 countries worldwide for the treatment of adult patients with unresectable or metastatic HER2 low (IHC 1+ or IHC 2+/ISH-) breast cancer who have received a prior systemic therapy in the metastatic setting or developed disease recurrence during or within six months of completing adjuvant chemotherapy based on the results from the DESTINY-Breast04 trial.
ENHERTU (5.4 mg/kg) is approved in the
ENHERTU (5.4 mg/kg) is approved in more than 50 countries worldwide for the treatment of adult patients with unresectable or metastatic NSCLC whose tumors have activating HER2 (ERBB2) mutations, as detected by a locally or regionally approved test, and who have received a prior systemic therapy based on the results from the DESTINY-Lung02 and/or DESTINY-Lung05 trials. Continued approval in
ENHERTU (6.4 mg/kg) is approved in more than 65 countries worldwide for the treatment of adult patients with locally advanced or metastatic HER2 positive (IHC 3+ or IHC 2+/ISH+) gastric or gastroesophageal junction adenocarcinoma who have received a prior trastuzumab-based regimen based on the results from the DESTINY-Gastric01, DESTINY-Gastric02 and/or DESTINY-Gastric06 trials. Continued approval in
ENHERTU (5.4 mg/kg) is approved in
About the ENHERTU Clinical Development Program
A comprehensive global clinical development program is underway evaluating the efficacy and safety of ENHERTU monotherapy across multiple HER2 targetable cancers. Trials in combination with other anticancer treatments, such as immunotherapy, also are underway.
About the Daiichi Sankyo and AstraZeneca Collaboration
Daiichi Sankyo and AstraZeneca entered into a global collaboration to jointly develop and commercialize ENHERTU in March 2019 and DATROWAY® in July 2020, except in
About the ADC Portfolio of Daiichi Sankyo
The Daiichi Sankyo ADC portfolio consists of seven ADCs in clinical development crafted from two distinct ADC technology platforms discovered in-house by Daiichi Sankyo.
The ADC platform furthest in clinical development is Daiichi Sankyo’s DXd ADC Technology where each ADC consists of a monoclonal antibody attached to a number of topoisomerase I inhibitor payloads (an exatecan derivative, DXd) via tetrapeptide-based cleavable linkers. The DXd ADC portfolio currently consists of ENHERTU, a HER2 directed ADC, and DATROWAY, a TROP2 directed ADC, which are being jointly developed and commercialized globally with AstraZeneca. Patritumab deruxtecan (HER3-DXd), a HER3 directed ADC, ifinatamab deruxtecan (I-DXd), a B7-H3 directed ADC, and raludotatug deruxtecan (R-DXd), a CDH6 directed ADC, are being jointly developed and commercialized globally with Merck & Co., Inc,
The second Daiichi Sankyo ADC platform consists of a monoclonal antibody attached to a modified pyrrolobenzodiazepine (PBD) payload. DS-9606, a CLDN6 directed PBD ADC, is the first of several planned ADCs in clinical development utilizing this platform.
Ifinatamab deruxtecan, patritumab deruxtecan, raludotatug deruxtecan, DS-3939 and DS-9606 are investigational medicines that have not been approved for any indication in any country. Safety and efficacy have not been established.
ENHERTU
Indications
ENHERTU is a HER2-directed antibody and topoisomerase inhibitor conjugate indicated for the treatment of adult patients with:
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Unresectable or metastatic HER2-positive (IHC 3+ or ISH positive) breast cancer who have received a prior anti-HER2-based regimen either:
– In the metastatic setting, or
– In the neoadjuvant or adjuvant setting and have developed disease recurrence during or within six months of completing therapy
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Unresectable or metastatic:
– Hormone receptor (HR)-positive, HER2-low (IHC 1+ or IHC 2+/ISH-) or HER2-ultralow (IHC 0 with membrane staining) breast cancer, as determined by an FDA-approved test, that has progressed on one or more endocrine therapies in the metastatic setting
– HER2-low (IHC 1+ or IHC 2+/ISH-) breast cancer, as determined by an FDA-approved test, who have received a prior chemotherapy in the metastatic setting or developed disease recurrence during or within 6 months of completing adjuvant chemotherapy
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Unresectable or metastatic non-small cell lung cancer (NSCLC) whose tumors have activating HER2 (ERBB2) mutations, as detected by an FDA-approved test, and who have received a prior systemic therapy
This indication is approved under accelerated approval based on objective 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 (IHC 3+ or IHC 2+/ISH positive) gastric or gastroesophageal junction (GEJ) adenocarcinoma who have received a prior trastuzumab-based regimen
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Unresectable or metastatic HER2-positive (IHC 3+) solid tumors who have received prior systemic treatment and have no satisfactory alternative treatment options
This indication is approved under accelerated approval based on objective 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 |
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Contraindications
None.
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. A higher incidence of Grade 1 and 2 ILD/pneumonitis has been observed in patients with moderate renal impairment. 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 1 level. Consider corticosteroid treatment as soon as ILD/pneumonitis is suspected (e.g., ≥0.5 mg/kg/day prednisolone or equivalent). For symptomatic ILD/pneumonitis (Grade 2 or greater), permanently discontinue ENHERTU. Promptly initiate systemic corticosteroid treatment as soon as ILD/pneumonitis is suspected (e.g., ≥1 mg/kg/day prednisolone or equivalent) and continue for at least 14 days followed by gradual taper for at least 4 weeks.
HER2-Positive, HER2-Low, and HER2-Ultralow Metastatic Breast Cancer, HER2-Mutant NSCLC, and Solid Tumors (Including IHC 3+) (5.4 mg/kg)
In patients with metastatic breast cancer, HER2-mutant NSCLC, and other solid tumors treated with ENHERTU 5.4 mg/kg, ILD occurred in
HER2-Positive Locally Advanced or Metastatic Gastric Cancer (6.4 mg/kg)
In patients with locally advanced or metastatic HER2-positive gastric or GEJ adenocarcinoma treated with ENHERTU 6.4 mg/kg, ILD occurred in
Neutropenia
Severe neutropenia, including febrile neutropenia, can occur in patients treated with ENHERTU. Monitor complete blood counts prior to initiation of ENHERTU and prior to each dose, and as clinically indicated. For Grade 3 neutropenia (Absolute Neutrophil Count [ANC] <1.0 to 0.5 x 109/L), interrupt ENHERTU until resolved to Grade 2 or less, then maintain dose. For Grade 4 neutropenia (ANC <0.5 x 109/L), interrupt ENHERTU until resolved to Grade 2 or less, then reduce dose by 1 level. For febrile neutropenia (ANC <1.0 x 109/L and temperature >38.3º C or a sustained temperature of ≥38º C for more than 1 hour), interrupt ENHERTU until resolved, then reduce dose by 1 level.
HER2-Positive, HER2-Low, and HER2-Ultralow Metastatic Breast Cancer, HER2-Mutant NSCLC, and Solid Tumors (Including IHC 3+) (5.4 mg/kg)
In patients with metastatic breast cancer, HER2-mutant NSCLC, and other solid tumors treated with ENHERTU 5.4 mg/kg, a decrease in neutrophil count was reported in
HER2-Positive Locally Advanced or Metastatic Gastric Cancer (6.4 mg/kg)
In patients with locally advanced or metastatic HER2-positive gastric or GEJ adenocarcinoma treated with ENHERTU 6.4 mg/kg, a decrease in neutrophil count was reported in
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. Assess LVEF prior to initiation of ENHERTU and at regular intervals during treatment as clinically indicated. Manage LVEF decrease through treatment interruption. When LVEF is >
HER2-Positive, HER2-Low, and HER2-Ultralow Metastatic Breast Cancer, HER2-Mutant NSCLC, and Solid Tumors (Including IHC 3+) (5.4 mg/kg)
In patients with metastatic breast cancer, HER2-mutant NSCLC, and other solid tumors treated with ENHERTU 5.4 mg/kg, LVEF decrease was reported in
HER2-Positive Locally Advanced or Metastatic Gastric Cancer (6.4 mg/kg)
In patients with locally advanced or metastatic HER2-positive gastric or GEJ adenocarcinoma treated with ENHERTU 6.4 mg/kg, no clinical adverse events of heart failure were reported; however, on echocardiography,
Embryo-Fetal Toxicity
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 7 months after the last dose of ENHERTU. Advise male patients with female partners of reproductive potential to use effective contraception during treatment with ENHERTU and for 4 months after the last dose of ENHERTU.
Additional Dose Modifications
Thrombocytopenia
For Grade 3 thrombocytopenia (platelets <50 to 25 x 109/L) interrupt ENHERTU until resolved to Grade 1 or less, then maintain dose. For Grade 4 thrombocytopenia (platelets <25 x 109/L) interrupt ENHERTU until resolved to Grade 1 or less, then reduce dose by 1 level.
Adverse Reactions
HER2-Positive, HER2-Low, and HER2-Ultralow Metastatic Breast Cancer, HER2-Mutant NSCLC, and Solid Tumors (Including IHC 3+) (5.4 mg/kg)
The pooled safety population reflects exposure to ENHERTU 5.4 mg/kg intravenously every 3 weeks in 2233 patients in Study DS8201-A-J101 (NCT02564900), DESTINY-Breast01, DESTINY-Breast02, DESTINYBreast03, DESTINY-Breast04, DESTINY-Breast06, DESTINY-Lung01, DESTINY-Lung02, DESTINY-CRC02, and DESTINY-PanTumor02. Among these patients,
HER2-Positive Metastatic Breast Cancer
DESTINY-Breast03
The safety of ENHERTU was evaluated in 257 patients with unresectable or metastatic HER2-positive breast cancer who received at least 1 dose of ENHERTU 5.4 mg/kg intravenously once every 3 weeks in DESTINY-Breast03. The median duration of treatment was 14 months (range: 0.7 to 30) for patients who received ENHERTU.
Serious adverse reactions occurred in
ENHERTU was permanently discontinued in
The most common (≥
HER2-Low and HER2-Ultralow Metastatic Breast Cancer
DESTINY-Breast06
The safety of ENHERTU was evaluated in 434 patients with unresectable or metastatic HER2-low (IHC 1+ or IHC 2+/ISH-) or HER2-ultralow (IHC 0 with membrane staining) breast cancer who received ENHERTU 5.4 mg/kg intravenously once every 3 weeks in DESTINY-Breast06. The median duration of treatment was 11 months (range: 0.4 to 39.6) for patients who received ENHERTU.
Serious adverse reactions occurred in
ENHERTU was permanently discontinued in
The most common (≥
DESTINY-Breast04
The safety of ENHERTU was evaluated in 371 patients with unresectable or metastatic HER2-low (IHC 1+ or IHC 2+/ISH-) breast cancer who received ENHERTU 5.4 mg/kg intravenously once every 3 weeks in DESTINY-Breast04. The median duration of treatment was 8 months (range: 0.2 to 33) for patients who received ENHERTU.
Serious adverse reactions occurred in
ENHERTU was permanently discontinued in
The most common (≥
HER2-Mutant Unresectable or Metastatic NSCLC (5.4 mg/kg)
DESTINY-Lung02 evaluated 2 dose levels (5.4 mg/kg [n=101] and 6.4 mg/kg [n=50]); however, only the results for the recommended dose of 5.4 mg/kg intravenously every 3 weeks are described below due to increased toxicity observed with the higher dose in patients with NSCLC, including ILD/pneumonitis.
The safety of ENHERTU was evaluated in 101 patients with HER2-mutant unresectable or metastatic NSCLC who received ENHERTU 5.4 mg/kg intravenously once every 3 weeks until disease progression or unacceptable toxicity in DESTINY-Lung02. Nineteen percent of patients were exposed for >6 months.
Serious adverse reactions occurred in
ENHERTU was permanently discontinued in
The most common (≥
HER2-Positive Locally Advanced or Metastatic Gastric Cancer (6.4 mg/kg)
The safety of ENHERTU was evaluated in 187 patients with locally advanced or metastatic HER2-positive gastric or GEJ adenocarcinoma in DESTINY-Gastric01. Patients intravenously received at least 1 dose of either ENHERTU (N=125) 6.4 mg/kg every 3 weeks or either irinotecan (N=55) 150 mg/m2 biweekly or paclitaxel (N=7) 80 mg/m2 weekly for 3 weeks. The median duration of treatment was 4.6 months (range: 0.7 to 22.3) for patients who received ENHERTU.
Serious adverse reactions occurred in
ENHERTU was permanently discontinued in
The most common (≥
HER2-Positive (IHC 3+) Unresectable or Metastatic Solid Tumors
The safety of ENHERTU was evaluated in 347 adult patients with unresectable or metastatic HER2-positive (IHC 3+) solid tumors who received ENHERTU 5.4 mg/kg intravenously once every 3 weeks in DESTINY-Breast01, DESTINY-PanTumor02, DESTINY-Lung01, and DESTINY-CRC02. The median duration of treatment was 8.3 months (range 0.7 to 30.2).
Serious adverse reactions occurred in
ENHERTU was permanently discontinued in
The most common (≥
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 after 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 7 months after the last dose. Males: Advise male patients with female partners of reproductive potential to use effective contraception during treatment with ENHERTU and for 4 months after 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.
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Geriatric Use: Of the 1741 patients with HER2-positive, HER2-low, or HER2-ultralow breast cancer treated with ENHERTU 5.4 mg/kg,
24% were ≥65 years and4.9% were ≥75 years. No overall differences in efficacy within clinical studies 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 (61% ) as compared to younger patients (52% ). Of the 101 patients with HER2-mutant unresectable or metastatic NSCLC treated with ENHERTU 5.4 mg/kg,40% were ≥65 years and8% were ≥75 years. No overall differences in efficacy or safety were observed between patients ≥65 years of age compared to younger patients. Of the 125 patients with HER2-positive locally advanced or metastatic gastric or GEJ adenocarcinoma treated with ENHERTU 6.4 mg/kg in DESTINY-Gastric01,56% were ≥65 years and14% were ≥75 years. No overall differences in efficacy or safety were observed between patients ≥65 years of age compared to younger patients. Of the 192 patients with HER2-positive (IHC 3+) unresectable or metastatic solid tumors treated with ENHERTU 5.4 mg/kg in DESTINY-PanTumor02, DESTINY-Lung01, or DESTINY-CRC02,39% were ≥65 years and9% were ≥75 years. No overall differences in efficacy or safety were observed between patients ≥65 years of age compared to younger patients. - Renal Impairment: A higher incidence of Grade 1 and 2 ILD/pneumonitis has been observed in patients with moderate renal impairment. Monitor patients with moderate renal impairment more frequently. The recommended dosage of ENHERTU has not been established for patients with severe renal impairment (CLcr <30 mL/min).
- Hepatic Impairment: In patients with moderate hepatic impairment, due to potentially increased exposure, closely monitor for increased toxicities related to the topoisomerase inhibitor, DXd. The recommended dosage of ENHERTU has not been established for patients with severe hepatic impairment (total bilirubin >3 times ULN and any AST).
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.
Please see accompanying full Prescribing Information, including Boxed WARNINGS, and Medication Guide.
About Daiichi Sankyo
Daiichi Sankyo is an innovative global healthcare company contributing to the sustainable development of society that discovers, develops and delivers new standards of care to enrich the quality of life around the world. With more than 120 years of experience, Daiichi Sankyo leverages its world-class science and technology to create new modalities and innovative medicines for people with cancer, cardiovascular and other diseases with high unmet medical need. For more information, please visit www.daiichisankyo.com.
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References
1 Casamayor M, et al. Ecancermedicalscience. 2018;12:883.
2 NCCN Clinical Practice Guidelines. Gastric Cancer. V.1.2025. Accessed March 2025.
3 ESMO. Gastric Cancer Living Guidelines, v 33.10. October 2022. Accessed March 2025.
4 Globocan 2022. Stomach Cancer. Accessed March 2025.
5 Abrahao-Machado LF, et al. World J Gastroenterol. 2016;22(19):4619-25.
6 Iqbal N, et al. Mol Biol Int. 2014:852748.
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