TOKYO, JAPAN, March 23, 2026
Daiichi Sankyo has announced that Japan’s Pharmaceuticals and Medical Devices Agency (PMDA) has approved an update to the prescribing information for ENHERTU® (trastuzumab deruxtecan), expanding its use to include second-line treatment of patients with HER2-positive metastatic gastric cancer. This milestone is based on results from the Phase 3 DESTINY-Gastric04 trial, which demonstrated a statistically significant improvement in overall survival, positioning ENHERTU as the first HER2-directed antibody-drug conjugate (ADC) to show survival benefit in this setting.
Phase 3 Trial Shows Significant Survival Benefit
The approval expansion is supported by the DESTINY-Gastric04 Phase 3 clinical trial, a global, randomized study evaluating ENHERTU in patients with HER2-positive unresectable or metastatic gastric or gastroesophageal junction cancer who had progressed after first-line therapy.
The study demonstrated a 30% reduction in the risk of death compared to standard treatment with ramucirumab plus paclitaxel, with median overall survival of 14.7 months versus 11.4 months, respectively. These results highlight a clinically meaningful improvement in patient outcomes, addressing a significant unmet need in second-line treatment options.
Importantly, prior to this study, no HER2-targeted therapy had demonstrated survival benefit in the second-line metastatic gastric cancer setting, making ENHERTU a groundbreaking advancement in oncology treatment. The findings were presented at a major global oncology conference and published in a leading medical journal, further validating their clinical significance.
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Advancing Antibody-Drug Conjugate Innovation
ENHERTU is a HER2-directed antibody-drug conjugate (ADC) developed using Daiichi Sankyo’s proprietary DXd technology platform, combining a monoclonal antibody with a potent topoisomerase I inhibitor payload. This design enables targeted delivery of chemotherapy directly to cancer cells, improving efficacy while minimizing damage to healthy tissues.
The expanded indication reinforces the growing importance of ADC therapies in oncology, which are transforming cancer treatment by offering precision-targeted approaches with improved therapeutic outcomes. ENHERTU is already approved in multiple countries for various cancers, including breast, lung, and gastric cancers, demonstrating its versatility and strong clinical performance.
The safety profile observed in the Phase 3 trial was consistent with previous studies, with no new safety concerns identified, further supporting the therapy’s use in broader patient populations. However, clinicians are advised to monitor for interstitial lung disease (ILD), a known risk associated with the treatment, emphasizing the importance of careful patient management and monitoring.
Addressing Unmet Need in Gastric Cancer Treatment
Gastric cancer remains one of the leading causes of cancer-related mortality worldwide, with particularly high incidence rates in Japan. In 2022 alone, more than 125,000 cases were diagnosed in Japan, with over 43,000 deaths, underscoring the urgent need for more effective treatment options. Approximately 20% of gastric cancers are HER2-positive, representing a significant patient population that can benefit from targeted therapies.
The expansion of ENHERTU’s indication to second-line treatment provides a new standard of care for patients with limited options, particularly those who have experienced disease progression after initial therapy. This advancement reflects Daiichi Sankyo’s commitment to innovative cancer research and addressing high unmet medical needs.
As the global oncology landscape continues to evolve, therapies like ENHERTU are expected to play a pivotal role in improving survival outcomes and advancing precision medicine, offering new hope for patients facing aggressive and hard-to-treat cancers.
Source: Daiichi Sankyo press release
