Datopotamab Deruxtecan Receives U.S. Breakthrough Therapy Status for Treated EGFR-Mutated Advanced NSCLC

Datopotamab deruxtecan (Dato-DXd) has recently received Breakthrough Therapy Designation (BTD) from the U.S. Food and Drug Administration (FDA) for treating adults with locally advanced or metastatic non-small cell lung cancer (NSCLC) that has progressed after treatments involving an EGFR tyrosine kinase inhibitor and platinum-based chemotherapy. This antibody drug conjugate (ADC) is specifically engineered to target TROP2 and was developed by Daiichi Sankyo in collaboration with AstraZeneca.

The FDA's BTD aims to expedite the development and review of drugs intended to treat severe conditions and meet significant unmet medical needs. To qualify, a drug must show preliminary clinical evidence indicating substantial improvement over existing treatments on clinically significant endpoints. For datopotamab deruxtecan, the BTD was granted based on the data from the TROPION-Lung05 phase 2 trial, supported by results from the TROPION-Lung01 phase 3 trial. These results, which were recently shared at the European Society of Medical Oncology (ESMO) Asia 2024 Congress, highlighted the potential of datopotamab deruxtecan in addressing the needs of patients with EGFR-mutated NSCLC.

Ken Takeshita, MD, Global Head of R&D at Daiichi Sankyo, emphasized the pressing need for new treatments for patients with previously treated EGFR-mutated NSCLC who have experienced disease progression. Takeshita expressed hope that datopotamab deruxtecan could significantly improve patient outcomes and indicated a commitment to working closely with the FDA to make the drug available as soon as possible. Susan Galbraith, Executive Vice President of Oncology R&D at AstraZeneca, also highlighted the importance of this designation, underscoring the potential of datopotamab deruxtecan to become a vital treatment option for these patients.

In addition to the BTD, Daiichi Sankyo and AstraZeneca recently filed a new Biologics License Application for the accelerated approval of datopotamab deruxtecan in the U.S., aiming to treat adult patients with advanced EGFR-mutated NSCLC who have previously undergone systemic therapies, including EGFR-directed therapies.

The TROPION-Lung05 trial is a global, multicenter, open-label phase 2 study examining the efficacy and safety of datopotamab deruxtecan in patients with advanced NSCLC who have progressed on at least one tyrosine kinase inhibitor and one regimen of platinum-based chemotherapy. The study enrolled 137 patients from Asia, Europe, and North America. Key endpoints include objective response rate (ORR), duration of response (DoR), disease control rate, progression-free survival (PFS), and overall survival (OS).

TROPION-Lung01 is another global, randomized, open-label phase 3 trial comparing datopotamab deruxtecan to docetaxel in patients needing systemic therapy after prior treatment. This study also includes patients with and without actionable genomic alterations, with previous treatments including platinum-based chemotherapy and PD-1 or PD-L1 inhibitors. The primary endpoints are progression-free survival and overall survival, with key secondary endpoints covering a range of efficacy and safety measures.

Non-small cell lung cancer represents about 80% of lung cancer cases, with a significant portion of these having EGFR mutations. While initial treatments with EGFR TKIs have improved outcomes, many patients eventually experience disease progression and require subsequent therapies. TROP2, a protein expressed in most NSCLC tumors, presents a promising target for new treatments like datopotamab deruxtecan, which currently has no approved ADC targeting it for lung cancer.

Datopotamab deruxtecan is part of a broader clinical development program involving numerous trials evaluating its efficacy and safety across various cancers, including NSCLC and different types of breast cancer. This investigational drug is among the most advanced programs in the ADC scientific platform being developed by Daiichi Sankyo and AstraZeneca.