Enhertu® Recommended for EU Approval by CHMP for Treatment of Previously Treated HER2-Positive Metastatic Solid Tumors
Enhertu® (trastuzumab deruxtecan), a HER2-directed antibody drug conjugate (ADC), has received a positive recommendation for approval in the European Union for the treatment of adult patients with unresectable or metastatic HER2-positive (IHC 3+) solid tumors who have previously received systemic therapy and have no satisfactory treatment alternatives.
The recommendation was issued by the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA). The decision is now subject to review by the European Commission, which holds the final authority to grant marketing authorization for medicines in the EU.
If approved, Enhertu would represent one of the first HER2-directed ADC therapies available across a broad range of HER2-overexpressing solid tumors in the European region, potentially addressing a significant unmet medical need in oncology.
A Broad Tumor-Agnostic Approach to HER2-Positive Cancer
The CHMP positive opinion is based on clinical data from three Phase 2 trials—DESTINY-PanTumor02, DESTINY-Lung01, and DESTINY-CRC02—which evaluated Enhertu in patients with HER2-positive (IHC 3+) metastatic solid tumors across multiple cancer types.
These tumor types included biliary tract, bladder, cervical, endometrial, ovarian, pancreatic, colorectal, lung, and other advanced solid tumors. In all studies, Enhertu demonstrated clinically meaningful and durable responses across a diverse patient population that had limited or no remaining treatment options.
The data collectively support a tumor-agnostic treatment approach targeting HER2 overexpression, reinforcing the potential of precision oncology to expand therapeutic options beyond traditional cancer classifications.
Clinical Trial Evidence Supporting the CHMP Recommendation
DESTINY-PanTumor02 Trial
DESTINY-PanTumor02 was a global, multicenter, open-label Phase 2 study evaluating Enhertu in patients with previously treated HER2-expressing solid tumors.
Among 111 patients with centrally or locally confirmed HER2-positive (IHC 3+) disease, Enhertu achieved a confirmed objective response rate (ORR) of 51.4%, with a 95% confidence interval of 41.7–61.0. The median duration of response (DOR) was 14.2 months, ranging from 10.3 to 23.6 months.
The overall study enrolled 267 patients across multiple tumor types, including biliary tract, bladder, cervical, endometrial, ovarian, pancreatic, and others. These results highlight meaningful anti-tumor activity across a wide spectrum of HER2-driven cancers.
DESTINY-Lung01 Trial
DESTINY-Lung01 evaluated Enhertu in patients with unresectable or metastatic non-small cell lung cancer (NSCLC) characterized by HER2 mutations or HER2 overexpression.
In the HER2-positive (IHC 3+) subgroup of 17 patients, Enhertu demonstrated a confirmed ORR of 52.9%, with a 95% confidence interval of 27.8–77.0. The median duration of response was 6.9 months, ranging from 4.0 to 11.7 months.
Although this subgroup was small, the response rate was considered clinically meaningful in a population with historically poor outcomes and limited treatment options.
DESTINY-CRC02 Trial
DESTINY-CRC02 focused on patients with previously treated HER2-positive metastatic colorectal cancer.
In this study, Enhertu demonstrated a confirmed ORR of 46.9% (95% CI: 34.3–59.8) among 64 HER2-positive (IHC 3+) patients. The median duration of response was 5.5 months, ranging from 1.3 to 9.7 months.
The study included 122 total patients randomized across two dosing regimens (5.4 mg/kg and 6.4 mg/kg), with additional patients enrolled in the 5.4 mg/kg arm during a second stage. The results supported both efficacy and dose optimization in this patient population.
Expert Perspectives on the CHMP Opinion
John Tsai, MD, Global Head of R&D at Daiichi Sankyo, emphasized the significance of the regulatory milestone, stating that the CHMP opinion recognizes Enhertu’s potential as a first-in-class HER2-directed ADC for a broad group of metastatic solid tumors in Europe.
He noted that patients with HER2-positive advanced cancers often face limited therapeutic choices, and Enhertu offers clinically meaningful responses across multiple tumor types where treatment options are scarce.
Susan Galbraith, MBBChir, PhD, Executive Vice President of Oncology R&D at AstraZeneca, highlighted the broader implications for precision oncology. She noted that while HER2-directed therapies have transformed outcomes in breast and gastric cancers, many other HER2-overexpressing cancers still lack approved targeted therapies. She described the CHMP recommendation as an important step toward expanding targeted treatment access across tumor types.
Safety Profile and Tolerability
Across clinical studies, Enhertu demonstrated a safety profile consistent with previous trials, with no new safety signals identified.
In DESTINY-PanTumor02, the most common Grade 3 or higher treatment-related adverse events among 267 patients included neutropenia (10.9%) and anemia (10.9%).
Interstitial lung disease (ILD) or pneumonitis occurred in 10.5% of patients. Most cases were Grade 1 or 2 in severity. There was one Grade 3 event (0.4%), no Grade 4 events, and three Grade 5 events (1.1%), as adjudicated by an independent committee.
In DESTINY-Lung01, ILD or pneumonitis occurred in 5% of patients, with most cases being low grade. One Grade 5 event (2%) was reported, along with an additional post–data cutoff case later adjudicated as drug-related Grade 5 pneumonitis.
In DESTINY-CRC02, ILD or pneumonitis occurred in 8% of patients, all of which were low grade (Grade 1 or 2), with no Grade 3–5 events reported.
Other common Grade 3 or higher adverse events across studies included neutropenia, anemia, fatigue, pneumonia, dyspnea, nausea, and leukopenia depending on the trial population.
Existing Global Approvals
Enhertu is already approved in multiple regions worldwide across several HER2-driven cancer indications, including:
- HER2-positive breast cancer in both early and metastatic settings
- HER2-low and HER2-ultralow breast cancer
- HER2-mutant non-small cell lung cancer
- HER2-positive gastric and gastroesophageal junction cancers
- Multiple additional tumor-agnostic or expanded indications in various countries
These approvals are based on pivotal DESTINY clinical trials, including DESTINY-Breast03, DESTINY-Breast04, DESTINY-Breast06, DESTINY-Lung02, DESTINY-Gastric01, and others.
The Enhertu Clinical Development Program
Enhertu continues to be evaluated in a broad global clinical development program investigating its use as monotherapy and in combination with other anticancer agents. The program spans multiple HER2-expressing tumor types and continues to explore both earlier and later lines of therapy.
The ongoing research aims to expand the understanding of HER2 biology and further establish ADCs as a cornerstone of precision oncology treatment strategies.
Daiichi Sankyo and AstraZeneca Collaboration
Enhertu is being jointly developed and commercialized by Daiichi Sankyo and AstraZeneca under a global strategic collaboration. Daiichi Sankyo leads manufacturing and supply responsibilities, while both companies share development and commercialization efforts globally, excluding Japan where Daiichi Sankyo retains exclusive rights.
The partnership also includes Datroway® (datopotamab deruxtecan), another ADC targeting TROP2.
ADC Portfolio and Pipeline Expansion
Daiichi Sankyo’s ADC portfolio is among the most advanced in oncology drug development. Built on the DXd ADC technology platform, the pipeline includes multiple investigational therapies targeting different tumor antigens.
Key investigational ADCs include:
- Ifinatamab deruxtecan (I-DXd)
- Patritumab deruxtecan (HER3-DXd)
- Raludotatug deruxtecan (R-DXd)
- DS-3939 and DS3790
- DS3610, a STING agonist-based ADC
These candidates are being developed either independently or in collaboration with partners such as Merck & Co.
All investigational agents mentioned remain unapproved, and their safety and efficacy have not yet been established.
The CHMP positive opinion for Enhertu marks a significant regulatory milestone in the European Union and reinforces the growing role of HER2 as a universal oncology target across multiple tumor types. If approved by the European Commission, Enhertu could become a transformative treatment option for patients with previously treated HER2-positive metastatic solid tumors who currently have limited or no effective therapies available.
The decision also highlights the broader shift toward biomarker-driven, tumor-agnostic cancer treatment strategies and further establishes antibody drug conjugates as a powerful modality in modern oncology.
About Daiichi Sankyo
Daiichi Sankyo (TSE: 4568) is a global healthcare company committed to becoming a trusted healthcare innovator, transforming the lives of people through its strength in science and technology. The company discovers and develops new standards of care to address diverse medical needs to fulfill its purpose of contributing to the enrichment of quality of life around the world. With a strategic focus on oncology, Daiichi Sankyo is advancing an industry-leading antibody drug conjugate portfolio along with identifying new breakthrough generating technologies to deliver practice-changing medicines to patients, healthcare professionals and society
