US Priority Review for Datopotamab Deruxtecan in EGFR-Mutated Advanced NSCLC

A promising development in lung cancer treatment is on the horizon as the Food and Drug Administration (FDA) aims to make a regulatory decision on datopotamab deruxtecan by the third quarter of 2025. This drug has already received Breakthrough Therapy Designation (BTD) for its potential to significantly improve outcomes for patients with advanced or metastatic non-small cell lung cancer (NSCLC) with EGFR mutations. The application for its approval is grounded in findings from several pivotal trials, including TROPION-Lung05, TROPION-Lung01, and TROPION-PanTumor01.

Datopotamab deruxtecan, developed by Daiichi Sankyo in collaboration with AstraZeneca, is a TROP2-directed DXd antibody drug conjugate (ADC). It has shown encouraging results, notably in achieving a confirmed objective response rate (ORR) of 42.7% with a median duration of response (DoR) of seven months among patients with previously treated advanced or metastatic EGFR-mutated NSCLC, as presented at the 2024 ESMO Asia Congress. The safety profile of the drug remains consistent with previous findings, indicating no new safety issues.

This drug represents a hopeful option for patients who have seen their diseases advance despite front-line therapies, including those involving EGFR-tyrosine kinase inhibitors. If approved, datopotamab deruxtecan would be the first TROP2-directed ADC available for lung cancer treatment, offering a novel approach for patients who have exhausted existing treatments.

Daiichi Sankyo and AstraZeneca are conducting extensive research on datopotamab deruxtecan, evaluating its efficacy both as a standalone treatment and in combination with other therapies. This research includes seven Phase III trials focused on NSCLC, such as TROPION-Lung14 and TROPION-Lung15, which explore the drug's potential alone and in combination with osimertinib for advanced EGFR-mutated nonsquamous NSCLC.

The global burden of lung cancer is immense, with nearly 2.5 million cases diagnosed in 2022. Non-small cell lung cancer (NSCLC) accounts for approximately 80% of these cases. Within this group, a significant subset of patients has tumors with EGFR mutations, particularly in Asia, where up to 40% of patients may be affected. The current standard treatment for patients with these mutations involves EGFR-TKIs, but many patients face disease progression, necessitating alternative therapies like chemotherapy. TROP2, a protein often found in NSCLC tumors, has not yet been targeted by any approved ADCs, emphasizing the potential impact of datopotamab deruxtecan.

The TROPION-Lung05 trial, a global Phase II study, evaluates the effectiveness and safety of datopotamab deruxtecan in patients with advanced NSCLC who have progressed on prior treatments, including TKIs and platinum-based chemotherapy. Results have been promising, highlighting the drug's potential as a new treatment option. The TROPION-Lung01 trial, a Phase III study, compares datopotamab deruxtecan with the chemotherapy drug docetaxel, showing significant improvements in progression-free survival (PFS).

Additionally, the TROPION-PanTumor01 Phase I trial assesses the safety and preliminary efficacy of datopotamab deruxtecan across a range of advanced solid tumors, further supporting the drug's potential application in various cancer treatments.

Datopotamab deruxtecan, already approved in Japan under the brand name Datroway for certain breast cancers, is undergoing a comprehensive global development program to evaluate its effectiveness across multiple cancers, including lung and breast cancer. This program involves more than 20 trials and aims to explore the drug's potential as both a monotherapy and in combination with other cancer treatments.

The collaboration between AstraZeneca and Daiichi Sankyo, initiated in 2020, underscores the commitment to advancing datopotamab deruxtecan as a transformative treatment for cancer patients worldwide, with Daiichi Sankyo overseeing its production and supply. This partnership is part of AstraZeneca's broader efforts to innovate in lung cancer treatment, aiming to bring patients closer to a cure and significantly enhance their quality of life through groundbreaking therapeutic advances.