AstraZeneca, Daiichi Sankyo Submit New BLA for Datopotamab in Lung Cancer

AstraZeneca and Daiichi Sankyo have submitted a new biologics license application (BLA) for accelerated approval for datopotamab deruxtecan (Dato-DXd) to treat adult patients with locally advanced or metastatic epidermal growth factor receptor-mutated (EGFR) non-small cell lung cancer (NSCLC).

The companies have withdrawn a previous BLA after feedback from regulators at the FDA. The original application was based on results from a phase 3 trial of Dato-DXd. Data released in September 2024 on this trial, TROPION-Lung01 phase 3, indicated that datopotamab deruxtecan improved overall survival, although it did not meet statistical significance. In the prespecified subgroup of patients with nonsquamous NSCLC, datopotamab deruxtecan showed a 2.3-month improvement in overall survival compared with docetaxel. But in patients with squamous NSCLC, consistent with the previous analysis, datopotamab deruxtecan did not show an overall survival improvement.

The new BLA is now based on results from the TROPION-Lung05 phase 2 trial and supported by data from the TROPION-Lung01 phase 3 and TROPION-PanTumor01 phase 1 trials. New results from a pooled analysis of patients will be featured in a late-breaking presentation at the upcoming European Society for Medical Oncology (ESMO) Asia 2024 Congress in December 2024.

A spokesperson for AstraZeneca said the results of TROPION-Lung01, together with data from TROPION-Lung05, showed benefit for patients with an EGFR mutation which informed the companies' discussions with the FDA and, ultimately, the decision to seek accelerated approval of datopotamab deruxtecan in this patient population.

In TROPION-Lung05, datopotamab deruxtecan showed benefit in the subset of 78 patients with an EGFR mutation including an objective response rate (ORR) of 43.6%, a disease control rate (DCR) of 82.1% and median duration of response (DoR) of 7.0 months. Datopotamab deruxtecan had a manageable safety profile consistent with previously reported data in NSCLC. These datat were presented at the European Society for Medical Oncology (ESMO) 2023 Congress.

Ken Takeshita, M.D.

“Treating EGFR-mutated non-small cell lung cancer is incredibly challenging following disease progression given that the complexity and variability of these mutations often lead to resistance,” Ken Takeshita, M.D., global head, R&D, at Daiichi Sankyo, said in a news release. “The potential approval of datopotamab deruxtecan could offer renewed hope for patients with this formidable disease.”

Datopotamab deruxtecan is a TROP2-directed antibody drug conjugate (ADC). TROP2 is a protein that is expressed in the majority of non-small cell lung cancer tumors. There is currently no TROP2-directed antibody drug conjugate approved to treat patients with lung cancer.

AstraZeneca and Daiichi Sankyo are evaluating datopotamab deruxtecan alone and with Tagrissso (osimertinib) to treat patients with advanced or metastatic EGFR-mutated nonsquamous NSCLC in the ongoing TROPION-Lung14 and TROPION-Lung15 phase 3 trials.