FDA Approves Datroway for EGFR-Mutated Advanced Lung Cancer

Datroway received accelerated FDA approval for adults with EGFR+ advanced NSCLC: © stock.adobe.com.

The U.S. Food and Drug Administration (FDA) granted accelerated approval to Datroway (datopotamab deruxtecan-dlnk) for adults with locally advanced or metastatic non-small cell lung cancer (NSCLC) that has an epidermal growth factor receptor (EGFR) mutation. This approval applies to patients whose disease has progressed following treatment with an EGFR-targeted therapy and platinum-based chemotherapy.

Efficacy was evaluated in a pooled subgroup of 114 patients with locally advanced or metastatic EGFR-mutated NSCLC who had previously been treated with an EGFR-targeted therapy and platinum-based chemotherapy. These patients received Datroway at the recommended dose across two clinical trials, TROPION-Lung05 and TROPION-Lung01.

The major efficacy outcome measures were confirmed overall response rate (ORR) and duration of response (DOR), as determined by blinded independent central review using RECIST version 1.1. The ORR was 45%, and the median DOR was 6.5 months.

The prescribing information for Datroway includes warnings and precautions for interstitial lung disease or pneumonitis, eye-related side effects, mouth inflammation (stomatitis), and risks to unborn babies.

The recommended dose of Datroway is 6 milligrams per kilogram (mg/kg), up to a maximum of 540 milligrams (mg) for patients who weigh 90 kilograms (kg) or more. It is given as an intravenous (IV) infusion once every three weeks until disease progression or unacceptable side effects.

The FDA reviewed this application using the Assessment Aid, a voluntary tool provided by the applicant to help streamline the review process.

This application also received priority review and breakthrough therapy designation, both of which are part of the FDA’s expedited programs. These programs are designed to help speed the development and review of treatments for serious or life-threatening conditions. More details about these pathways can be found in the FDA’s Guidance for Industry on expedited programs.

Previous Study Findings for Datroway

For patients with advanced or metastatic NSCLC with actionable genomic alterations, encouraging and durable antitumor activity was observed during treatment with Datroway, according to study findings published in the Journal of Clinical Oncology.

Grade 3 (severe) or worse treatment-related side effects was similar with previous observations, with no new observed safety signals.

“[Datroway] elicited promising [objective response rates], durable responses, and an acceptable safety profile in heavily pretreated patients with advanced NSCLC and actionable genomic alterations, including in the two predominant EGFR-mutation and ALK-rearrangement subgroups,” study authors wrote. “These findings suggest that this novel TROP2-directed [antibody-drug conjugate] may provide clinically meaningful benefit in a difficult-to-treat population with poor prognosis and lack of effective therapies.”

After a median treatment duration of 4.4 months, the confirmed overall response rate was 35.8%, including 43.6% in patients with EGFR mutations and 23.5% of those with ALK rearrangements. The median duration of response was seven months, and the overall disease control rate was 78.8%.

Regarding safety, grade 3 or worse treatment-related side effects occurred in 28.5% of patients. The most common side effect was stomatitis, occurring in 56.2% of patients at any grade and in 9.5% at grade 3 or higher. Treatment-related interstitial lung disease or pneumonitis occurred in five patients (3.6%), including one fatal event (0.7%).

Overall, 129 patients (94.2%) experienced treatment-related side effects, with dose reductions in 27 patients (19.7%), dose delays in 29 (21.2%) and discontinuations in seven (5.1%).

Datroway is a TROP2-directed antibody-drug conjugate with a highly potent topoisomerase 1 inhibitor payload, designed to deliver chemotherapy directly to cancer cells.

Notably, Datroway was also approved for patients with unresectable or metastatic, hormone receptor-positive, HER2-negative breast cancer, following prior therapies, earlier this year.

Reference

1. “Datopotamab Deruxtecan in Advanced or Metastatic Non–Small Cell Lung Cancer With Actionable Genomic Alterations: Results From the Phase II TROPION-Lung05 Study,” by Dr. Jacob Sands, et al., Journal of Clinical Oncology.
2. “FDA grants accelerated approval to datopotamab deruxtecan-dlnk for EGFR-mutated non-small cell lung cancer,” U.S. Food and Drug Administration. Accessed June 23, 2025.

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