AstraZeneca and Daiichi Sankyo Seek Accelerated Approval for Datopotamab Deruxtecan in EGFR-Mutated NSCLC
Key Insights
AstraZeneca and Daiichi Sankyo submitted a Biologics License Application to the FDA for datopotamab deruxtecan to treat advanced EGFR (search)-mutated non-small cell lung cancer (search).
The BLA is based on Phase II TROPION-Lung05 trial results, evaluating the drug's efficacy and safety in patients who progressed after platinum-based chemotherapy and a TKI.
The companies withdrew a previous BLA for the drug in advanced or metastatic nonsquamous NSCLC based on the TROPION-Lung01 Phase III trial data.
AstraZeneca and Daiichi Sankyo have submitted a Biologics License Application (BLA) to the FDA seeking accelerated approval for datopotamab deruxtecan (Dato-DXd) for the treatment of adult patients with previously treated, advanced epidermal growth factor receptor-mutated (EGFR (search)) non-small cell lung cancer (search) (NSCLC). This submission is based on data from the Phase II TROPION-Lung05 trial.
TROPION-Lung05 Trial Data
The TROPION-Lung05 trial is a global, multicenter, single-arm, open-label study assessing the efficacy and safety of datopotamab deruxtecan in patients with locally advanced or metastatic NSCLC harboring actionable genomic alterations. These patients had previously progressed on or after one regimen of platinum-based chemotherapy and at least one tyrosine kinase inhibitor (TKI). The trial's primary endpoint was objective response rate (ORR) as evaluated by blinded independent central review (BICR). Secondary endpoints included duration of response (DoR), disease control rate (DCR), clinical benefit rate, progression-free survival (PFS), time to response (TTR), overall survival (OS), and safety.
Strategic Shift and Prior Trial Data
In conjunction with this submission, AstraZeneca and Daiichi Sankyo have withdrawn a previous BLA for datopotamab deruxtecan in patients with advanced or metastatic nonsquamous NSCLC. This prior application was based on the TROPION-Lung01 Phase III trial. According to AstraZeneca, the decision to focus on the EGFR (search)-mutated population was informed by the TROPION-Lung01 results, which, along with data from TROPION-Lung05, showed a pronounced benefit in patients with EGFR mutations.
Susan Galbraith, EVP, Oncology R&D, AstraZeneca, stated that the TROPION-Lung01 trial was designed to assess the potential of improving upon standard-of-care chemotherapy in a broad, previously treated, advanced lung cancer patient population and has provided exciting exploratory data supporting biomarker development.
Ongoing and Planned Trials
Currently, AstraZeneca and Daiichi Sankyo are evaluating datopotamab deruxtecan in combination with Tagrisso (osimertinib) in the ongoing TROPION-Lung14 and TROPION-Lung15 Phase III trials, specifically targeting patients with advanced or metastatic EGFR (search)-mutated nonsquamous NSCLC. An additional trial in patients with biomarker-positive tumors in the 2nd-line nonsquamous NSCLC setting is also in the planning stages.
NSCLC and EGFR Mutations: A Significant Challenge
NSCLC accounts for approximately 80% to 85% of all lung cancer cases, making it the most common form. The American Cancer Society estimates that there will be 234,580 new cases of lung cancer in the United States this year, with 125,070 deaths expected. NSCLC remains the leading cause of cancer-related deaths in the U.S., accounting for one in every five deaths.
A 2016 study published in The National Institutes of Health estimated that approximately 32.3% of all patients with NSCLC have EGFR (search) mutations.
Ken Takeshita, MD, Global Head, R&D, Daiichi Sankyo, emphasized the challenges in treating EGFR (search)-mutated NSCLC following disease progression, noting that the complexity and variability of these mutations often lead to resistance. He stated that the potential approval of datopotamab deruxtecan could offer renewed hope for patients with this disease.