FDA Grants Breakthrough Status to Datopotamab Deruxtecan for EGFR+ Lung Cancer

The FDA has granted Breakthrough Therapy Designation to datopotamab deruxtecan (Dato-DXd) for advanced EGFR-mutated non-small cell lung cancer (NSCLC). Backed by robust data from the TROPION-Lung05 and TROPION-Lung01 trials, this TROP2-targeted antibody-drug conjugate offers hope for improved outcomes in NSCLC patients who have exhausted standard therapies.

Developed jointly by AstraZeneca and Daiichi Sankyo, this investigational therapy targets patients whose disease has progressed after treatment with EGFR-tyrosine kinase inhibitors (TKIs) and platinum-based chemotherapy.

Susan Galbraith, Executive Vice President of Oncology R&D at AstraZeneca, emphasized the importance of this development: “This Breakthrough Therapy Designation reinforces datopotamab deruxtecan as a promising potential therapy for patients with EGFR-mutated lung cancer who continue to face significant unmet needs following disease progression on or after initial treatments.”

Groundbreaking Trials Support Approval

The FDA's decision was informed by compelling data from the TROPION-Lung05 Phase II trial, supported by additional evidence from the TROPION-Lung01 Phase III trial. These studies evaluated the efficacy and safety of datopotamab deruxtecan in treating NSCLC, showcasing promising clinical results.

The TROPION-Lung05 trial focused on patients with genomic alterations, including EGFR mutations, who had undergone at least one round of TKI therapy and platinum-based chemotherapy. Key outcomes, such as the objective response rate (ORR) and other secondary endpoints, demonstrated the potential of datopotamab deruxtecan in addressing disease progression. The trial enrolled 137 patients globally, reflecting a diverse patient population.

The larger TROPION-Lung01 trial, with over 600 participants, directly compared datopotamab deruxtecan to the chemotherapy agent docetaxel. The study highlighted notable improvements in progression-free survival (PFS) and overall survival (OS), further solidifying the drug's efficacy.

A Game-Changing Therapy

Datopotamab deruxtecan is an advanced antibody-drug conjugate (ADC) targeting the TROP2 protein, frequently overexpressed in several cancers, including NSCLC. Engineered using Daiichi Sankyo’s proprietary DXd ADC technology, the drug delivers a potent chemotherapy payload directly to cancer cells, minimizing damage to healthy tissues.

Dr. Ken Takeshita, Global Head of R&D at Daiichi Sankyo, expressed optimism: Datopotamab deruxtecan has the potential to play an important role in improving outcomes and we look forward to working closely with the FDA to bring this medicine to patients as quickly as possible.”

As a cornerstone of the AstraZeneca and Daiichi Sankyo oncology pipelines, datopotamab deruxtecan is also being tested across multiple cancers, including breast cancer and other subtypes of lung cancer. Seven Phase III trials are ongoing in lung cancer alone, exploring the drug’s potential as both a monotherapy and in combination with other treatments.

AstraZeneca and Daiichi Sankyo have already submitted a Biologics License Application (BLA) to the FDA, seeking accelerated approval for datopotamab deruxtecan. If approved, this could mark a significant advancement in the treatment landscape for EGFR-mutated NSCLC, providing patients with a targeted, effective option after exhausting standard therapies.