Key Takeaways
FDA Accelerated Approval for Datroway: Datroway (datopotamab deruxtecan) has received accelerated approval in the United States for advanced EGFR-mutated non-small cell lung cancer after prior EGFR and chemotherapy treatment.
Strong Efficacy and Safety Data: In the TROPION-Lung05 trial, Datroway showed a 45% objective response rate and a 78.8% disease control rate, with manageable safety across multiple studies.
First TROP2-Directed Option in Lung Cancer: Datroway is now the first approved TROP2-directed antibody-drug conjugate for lung cancer, expanding treatment options for heavily pretreated patients.
The FDA has granted accelerated approval to AstraZeneca and Daiichi Sankyo’s Datroway (datopotamab deruxtecan or Dato-DXd) for the treatment of adults with previously treated, locally advanced or metastatic EGFR-mutated non-small cell lung cancer (NSCLC). The approval, which was granted under the FDA’s Priority Review and Breakthrough Therapy Designation pathways, is based on objective response rate (ORR) and duration of response (DoR) data from the Phase II TROPION-Lung05 trial and supported by results from the Phase III TROPION-Lung01 trial.1
How Does Datroway Address Unmet Needs in Previously Treated EGFR-Mutated Lung Cancer?
“Addressing disease progression in patients with advanced EGFR-mutated lung cancer after prior targeted therapy and chemotherapy is very challenging with limited later-line treatment options available,” said Jacob Sands, MD, medical oncology, Dana-Farber Cancer Institute, trial investigator, in the press release. “The US approval of datopotamab deruxtecan introduces a novel and needed treatment option to patients with advanced disease.”
TROPION-Lung05 Trial Design and Endpoints
- The global, multicenter, single-arm, open-label TROPION-Lung05 trial evaluated the safety and efficacy of Datroway in 137 patients with locally advanced or metastatic NSCLC with actionable genomic alterations who had progressed on at least one EGFR-directed therapy and platinum-based chemotherapy across Asia, Europe, and North America.
- The primary endpoint of the trial was ORR as assessed by blinded independent central review.
- Secondary endpoints included DOR, disease control rate (DCR), clinical benefit rate, progression-free survival, time to response, overall survival, and safety.1
Clinical Efficacy and Safety Outcomes
- In both trials, Datroway demonstrated an ORR of 45%, with complete responses in 4.4% of patients and partial responses in 40%. The median DOR was 6.5 months.
- Additional primary results from TROPION-Lung05 showed a 78.8% DCR.
- Grade ≥3 treatment-related adverse events were reported in 28.5% of patients, with stomatitis being the most common.
- Notably, five patients developed adjudicated treatment-related interstitial lung disease or pneumonitis, including one fatal case.
- The safety profile of Datroway, which was was evaluated in a pooled analysis of 125 patients in the TROPION-Lung05, TROPION-Lung01 and TROPION-PanTumor01 trials, was found to be consistent with the known profile of the treatment, with no new safety signals identified.1,2
Strategic and Patient-Centric Perspectives
“This first approval of Datroway in lung cancer provides a much-needed option to patients with advanced EGFR-mutated lung cancer whose disease has become resistant to past treatments, regardless of the driving mutation,” said Dave Fredrickson, EVP, oncology hematology business unit, AstraZeneca, in the press release. “We have long supported patients with EGFR-mutated lung cancer and are proud to bring another innovative treatment option to this community.”
The Broader Impact of Lung Cancer in the US
According to the American Cancer Society, NSCLC accounts for approximately 87% of all lung cancer cases. Lung cancer is the second most common cancer among men and women in the United States and remains the leading cause of cancer-related death, responsible for about 20% of all cancer deaths. More people die from lung cancer each year than from colon, breast, and prostate cancers combined.3
Expanding the Clinical Development Program
AstraZeneca and Daiichi Sankyo are currently evaluating Datroway as a monotherapy and in combination with Tagrisso (osimertinib) in EGFR-mutated NSCLC in the ongoing Phase III TROPION-Lung14 and TROPION-Lung15 trials.1
“With today’s accelerated approval, Datroway is now the first TROP2-directed medicine available for certain patients in the US living with lung cancer,” said Ken Keller, global head, oncology business, president, CEO, Daiichi Sankyo, in the press release. “We remain committed to our extensive clinical development program to further identify where Datroway may be used in other types of lung and breast cancer.”
References
- Datroway approved in the US for patients with previously treated advanced EGFR-mutated non-small cell lung cancer. AstraZeneca. June 23, 2025. Accessed June 24, 2025. https://www.astrazeneca.com/media-centre/press-releases/2025/datroway-approved-in-us-for-egfrm-lung-cancer.html
- Datopotamab Deruxtecan in Advanced or Metastatic Non–Small Cell Lung Cancer With Actionable Genomic Alterations: Results From the Phase II TROPION-Lung05 Study. ASCO. Accessed June 24, 2025, https://ascopubs.org/doi/10.1200/JCO-24-01349
- Key Statistics for Lung Cancer. American Cancer Society. Accessed June 24, 2025. https://www.cancer.org/cancer/types/lung-cancer/about/key-statistics.html
