Datroway Gains Accelerated FDA Approval for Previously Treated EGFR-Mutated Advanced Non-Small Cell Lung Cancer
The U.S. Food and Drug Administration (FDA) has granted accelerated approval to Datroway (datopotamab deruxtecan, also referred to as Dato-DXd) for the treatment of adult patients with locally advanced or metastatic epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC) who have previously received EGFR-targeted therapy followed by platinum-based chemotherapy. This regulatory milestone marks an important step forward in addressing a critical unmet need for patients whose cancers have progressed despite multiple lines of therapy.
The approval was awarded under the FDA’s Accelerated Approval Program, which allows for the earlier approval of drugs that treat serious conditions and fill an unmet medical need based on a surrogate endpoint. In this case, the approval of Datroway was based on its objective response rate (ORR) and duration of response (DoR), as demonstrated in clinical trials. Continued approval for this indication will depend on the verification and description of clinical benefit in confirmatory studies.
A New Option for a Difficult-To-Treat Population
Lung cancer remains the leading cause of cancer-related death globally, with NSCLC accounting for approximately 85% of all cases. Among these, EGFR mutations are present in about 10-15% of Caucasian patients and up to 50% of Asian patients with NSCLC. While EGFR-targeted therapies have substantially improved outcomes in this molecularly defined subgroup, resistance eventually develops in most patients, limiting the durability of response and creating an urgent need for new treatments.
Dr. Jacob Sands, a medical oncologist at Dana-Farber Cancer Institute and an investigator in both the TROPION-Lung05 and TROPION-Lung01 trials, underscored the importance of Datroway’s approval:
“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. The US approval of datopotamab deruxtecan introduces a novel and needed treatment option to patients with advanced disease.”
Datroway is a TROP2-directed antibody-drug conjugate (ADC), specifically engineered with Daiichi Sankyo’s proprietary DXd payload technology. TROP2 is a cell surface glycoprotein expressed in many epithelial cancers, including NSCLC, and is associated with tumor growth and poor prognosis. Datroway uses a targeted delivery mechanism to release a cytotoxic agent directly into cancer cells expressing TROP2, offering a potentially effective and selective therapeutic strategy.
Clinical Evidence Supporting Approval
The FDA’s decision was supported by compelling clinical data from two key trials: the Phase II TROPION-Lung05 trial and the Phase III TROPION-Lung01 trial. In a subgroup analysis of patients with EGFR-mutated disease from these trials, Datroway demonstrated a confirmed objective response rate of 45% (95% confidence interval: 35-54), as assessed by blinded independent central review (BICR). Among the 114 patients evaluated, complete responses were observed in 4.4% of patients, and partial responses occurred in 40%. The median duration of response was 6.5 months (95% CI: 4.2-8.4), highlighting the potential of this ADC to provide sustained benefit in a heavily pretreated patient population.
The safety profile of Datroway was assessed through a pooled analysis of 125 patients enrolled across the TROPION-Lung05, TROPION-Lung01, and TROPION-PanTumor01 studies. Overall, the safety findings were consistent with prior knowledge of the drug, with no new safety signals observed. The manageable toxicity profile supports Datroway’s use in this setting, where balancing efficacy with tolerability is critical given the patients’ extensive treatment history.
Strategic Collaboration and Development Plans
Datroway is the result of a research and development collaboration between AstraZeneca and Daiichi Sankyo. The ADC was originally discovered by Daiichi Sankyo and is being co-developed and co-commercialized by both companies under a strategic partnership that was first established in 2020.
Dave Fredrickson, Executive Vice President of AstraZeneca’s Oncology Business Unit, emphasized the importance of this regulatory advancement:
“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. We have long supported patients with EGFR-mutated lung cancer and are proud to bring another innovative treatment option to this community.”
Ken Keller, Global Head of Oncology Business and President and CEO of Daiichi Sankyo, Inc., added:
“With today’s accelerated approval, Datroway is now the first TROP2-directed medicine available for certain patients in the US living with lung cancer. 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.”
The development program for Datroway is ongoing, with additional clinical trials aimed at expanding its use in earlier lines of therapy and other tumor types. In particular, AstraZeneca and Daiichi Sankyo are evaluating the combination of Datroway with Tagrisso (osimertinib)—a third-generation EGFR tyrosine kinase inhibitor—in Phase III studies (TROPION-Lung14 and TROPION-Lung15) to explore its utility in broader EGFR-mutated NSCLC treatment settings.
Patient Advocacy and Perspectives
Andrea E. Ferris, President and CEO of LUNGevity Foundation, a prominent U.S.-based lung cancer advocacy organization, welcomed the FDA’s decision:
“For people with advanced EGFR-mutated non-small cell lung cancer whose disease progresses on initial treatments, additional options are limited. Today’s approval of Datroway offers a new treatment option for patients whose disease has progressed following treatment with an EGFR-directed therapy and chemotherapy.”
The sentiment echoes the growing call for personalized, biomarker-driven treatment approaches in oncology. Datroway’s approval represents a convergence of scientific innovation, targeted therapy, and patient-centered care.
Financial Considerations
Under the terms of the existing agreement between the two companies, the U.S. approval of Datroway for EGFR-mutated advanced NSCLC triggers a $45 million milestone payment from AstraZeneca to Daiichi Sankyo. As outlined in their 2020 collaboration agreement, Daiichi Sankyo retains responsibility for recognizing sales of Datroway in the United States. This milestone is one of several structured into the deal to support continued co-development and commercialization.
The approval also sets the stage for broader commercial rollout and potential label expansion, contingent upon additional clinical trial results. The partners are expected to continue investing in trials that evaluate Datroway in both lung and breast cancer, two disease areas where TROP2 expression is prevalent and where patients continue to face limited treatment options after progression on standard therapies.
The accelerated approval of Datroway signals an important advancement in the evolving treatment landscape for NSCLC, particularly for patients with EGFR mutations who have exhausted standard options. By introducing the first TROP2-targeting ADC to this patient population, AstraZeneca and Daiichi Sankyo have opened new avenues for precision oncology and reaffirmed the potential of antibody-drug conjugates in solid tumors.
As additional data emerge from the ongoing Phase III studies and confirmatory trials, the medical community will be closely watching to determine the long-term place of Datroway in the NSCLC treatment paradigm. For now, this approval offers renewed hope to patients navigating the challenges of advanced EGFR-mutated lung cancer.
