FDA Accepts Dato-DXd Application for Non-Small Cell Lung Cancer


The FDA has accepted the biologics license application of datopotamab deruxtecan for the treatment of nonsquamous non-small cell lung cancer.

Lung Cancer: © Crystal Light - stock.adobe.com

Lung Cancer: © Crystal Light - stock.adobe.com

  • Datopotamab deruxtecan (Dato-DXd) is an engineered TROP2-directed antibody-drug conjugate (ADC) being investigated in nonsquamous non-small cell lung cancer (NSCLC).
  • The biologics license application (BLA) is supported by data from the phase 3 TROPION-Lung01 trial (NCT04656652).
  • A Prescription Drug User Fee Act (PDUFA) target action date is expected in the fourth quarter of 2024.

The BLA for Dato-DXd, a TROP2-directed ADC, in previously treated, advanced, nonsquamous NSCLC has been accepted by the FDA, and a PDUFA target action date is anticipated in the fourth quarter of 2024.1

The application is supported by findings from the phase 3 TROPION-Lung01 trial. Dato-DXd demonstrated superior progression-free survival (PFS) compared with the current standard-of-care treatment docetaxel. Interim results also favor Dato-DXd over docetaxel for overall survival (OS), but the numbers are not yet at statistical significance.

“The take home here was that Dato-DXd was a better tolerated drug from a global perspective, although there are some clear differences in terms of toxicity profile. It appears to be a potential new, meaningful therapy for patients with non-squamous metastatic advanced non-small cell lung cancer eligible for second-line chemotherapy,” said Aaron Lisberg, MD, thoracic medical oncologist at the University of California, Los Angeles, said in an interview with Targeted OncologyTM.

“Datopotamab deruxtecan has the potential to offer patients with previously treated advanced nonsquamous non-small cell lung cancer an effective and tolerable alternative to conventional chemotherapy. With regulatory discussions ongoing around the world and a parallel submission underway in the [United States] in breast cancer, this is only the beginning of our efforts to make this novel treatment available to patients as quickly as possible,” said Susan Galbraith, executive vice president of oncology research and development at AstraZeneca, in a press release.1

About TROPION-Lung01

Lisberg presented findings from TROPION-Lung01 at the 2023 European Society of Medical Oncology Congress. The median PFS, which was a dual primary end point of the study, was 4.4 months (95% CI, 4.2-5.6) with Dato-DXd vs 3.7 months with docetaxel (HR, 0.75; 95% CI, 0.62-0.91; P =.004).2

The overall response rate (ORR) with Dato-DXd was 26.4% (95% CI, 21.5%-31.8%) vs 12.8% (95% CI, 9.3%-17.1%) with docetaxel. The median duration of response with Dato-DXd was 7.1 months (95% CI, 5.6-10.9) compared with 5.6 months (95% CI, 5.4-8.1) with docetaxel.

Specially for patients with nonsquamous histology, the median PFS was 5.6 months (95% CI, 4.4-7.0) in the Dato-DXd arm vs 3.7 months (95% CI, 2.9-4.2) in the docetaxel arm (HR, 0.63; 95% CI, 0.51-0.78), the ORR was 31.2% vs 12.8%, and the DOR was 7.7 months vs 5.6 months, respectively.

At the interim analysis, the median OS was 12.4 months (95% CI, 10.8-14.8) with Dato-DXd vs 11.0 months (95% CI, 9.8-12.5) with docetaxel (HR, 0.90; 95% CI, 0.72-1.13) among the entire intent-to-treat population. The HR was 0.77 (95% CI, 0.59-1.01) for patients with nonsquamous histology.

1. Datopotamab deruxtecan biologics license application accepted in the US for patients with previously treated advanced nonsquamous non-small cell lung cancer. News release. AstraZeneca. February 19, 2024. Accessed February 19, 2024. http://tinyurl.com/w595xw6u
2. Ahn MJ, Lisberg A, Paz-Ares L, et al. Datopotamab deruxtecan (Dato-DXd) vs docetaxel in previously treated advanced/metastatic (adv/met) non-small cell lung cancer (NSCLC): results of the randomized phase 3 study TROPION-Lung01. Ann Oncol. 2023;34(suppl 2):S1305-S1306. doi:10.1016/j.annon
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