A new biologics license application (BLA) has been submitted to the Food and Drug Administration (FDA) seeking the accelerated approval of datopotamab deruxtecan (Dato-DXd) for the treatment of adult patients with previously treated, locally advanced or metastatic EGFR-mutated non-small cell lung cancer (NSCLC), according to a news release from AstraZeneca.
According to the FDA’s website, a BLA is a request for permission to introduce or deliver for introduction, a biologic product into interstate commerce.
The news release also reported that both AstraZeneca and Daiichi Sankyo (the joint developers of Dato-DXd) have withdrawn their BLA for the agent in the United States for patients with advanced or metastatic nonsquamous NSCLC. This withdrawal is based on phase 3 data from the TROPION-Lung01 trial. Feedback from the FDA informed the decision to submit a new BLA for patients within this population and subsequently withdraw the previously submitted BLA for nonsquamous NSCLC.
The new BLA submission is based on phase 2 data from the TROPION-Lung05 trial, as well as supported by phase 1 data from the TROPION-Lung01 study and phase 3 findings from the TROPION-PanTumor01 trial. Notably, updated findings will be presented at the upcoming European Society for Medical Oncology Asia 2024 Congress; a pooled analysis of patients with previously treated EGFR-mutated NSCLC who were enrolled in the TROPION-Lung05 and TROPION-Lung01 trials will be featured in a late-breaking presentation.
Glossary
Biologics License Application (BLA): a request to the FDA to allow a biologic product to be sold across state lines.
Clinical benefit rate (CBR): the percentage of patients who experience a complete or partial response, or stable disease for at least six months, as a result of therapy.
Disease control rate (DCR): the percentage of patients with advanced cancer who have a complete response, partial response or stable disease after treatment.
Duration of response (DoR): a clinical end point in cancer research that measures how long a patient responds to treatment without their cancer growing or spreading.
Locally Advanced Disease: Cancer that has spread from where it originally started to nearby tissues or lymph nodes but has not yet spread to other parts of the body
Metastatic: Cancer that has spread from where it originally started.
Overall survival: the time when a patient with cancer is still alive.
Objective response rate (ORR): The percentage of patients who have a partial or complete response to treatment within a certain time period.
Progression-free survival: the time during and after treatment when a patient with cancer lives with the disease without worsening.
Time to response: the length of time it takes for a patient's cancer to show a measurable response after starting a new treatment regimen.
“TROPION-Lung01 was designed to test the potential to improve upon standard-of-care chemotherapy in a broad, previously treated, advanced lung cancer patient population. The results, together with data from TROPION-Lung05, showed an especially pronounced benefit for patients with an EGFR mutation which informed our discussions with the FDA and the decision to seek accelerated approval of [Dato-DXd] in this patient population,” Susan Galbraith, executive vice president of oncology and R&D at AstraZeneca, stated in the news release. “TROPION-Lung01 has also provided exciting exploratory data supporting our biomarker development, which will be validated in ongoing and planned Phase III lung cancer trials.”
The phase 2 TROPION-Lung05 trial aims to better understand the efficacy and safety of Dato-DXd for the treatment of patients with locally advanced or metastatic NSCLC with actionable genomic alterations who have progressed on or after one regimen of platinum-based chemotherapy and at least one tyrosine kinase inhibitor (TKI). The primary end point of TROPION-Lung05 is the objective response rate (ORR). Duration of response (DoR), disease control rate (DCR), clinical benefit rate, progression-free survival (PFS), time to response (RRE), overall survival (OS) and safety serve as the trial’s secondary efficacy end points.
TROPION-Lung01 is evaluating the efficacy and safety of Dato-DXd versus docetaxel in adult patients with locally advanced or metastatic NSCLC with and without actionable genomic alterations who require systemic therapy following prior treatment. The dual primary end points of the study are PFS and OS, though investigator-assessed PFS, ORR, DoR, TTR, DCR and safety serve as key secondary end points.
The phase 1 TROPION-PanTumor01 study is a first-in-human evaluation of the safety and preliminary efficacy of Dato-DXd for patients with relapsed/refractory advanced solid tumors. Safety end points of the investigation include dose-limiting toxicities and serious side effects. Efficacy end points include ORR, DoR, TTR, PFS and OS, while pharmacokinetic, biomarker and immunogenicity end points also are being evaluated.
Although patients with EGFR-mutated NSCLC may be treated with an EGFR TKI, most patients eventually experience disease progression and receive chemotherapy. This therefore creates a gap in the treatment of patients within this population.
To address this, the TROP2-directed antibody-drug conjugate (ADC) Dato-DXd is under investigation. The ADC is comprised of a humanized anti-TROP2 IgG1 monoclonal antibody and attaches to a number of topoisomerase I inhibitor payloads by way of tetrapeptide-based cleavable linkers. At present, there are more than 20 trials evaluating the efficacy and safety of Dato-DXd across multiple cancers, including NSCLC.
In the news release, Dr. Ken Takeshita, global head of R&D at Daiichi Sankyo, stated: “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. The potential approval of Dato-DXd could offer renewed hope for patients with this formidable disease.”
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