AstraZeneca, Daiichi Sankyo ADC Fails Phase III NSCLC Trial

AstraZeneca and Daiichi Sankyo have recently unveiled new data from their Phase III TROPION-Lung01 clinical trial. The study investigates the efficacy of the antibody-drug conjugate (ADC) datopotamab deruxtecan (Dato-DXd) in treating non-small cell lung cancer (NSCLC). Unfortunately, the treatment did not achieve a statistically significant improvement in overall survival (OS) when compared to docetaxel, a standard chemotherapy drug.

The companies disclosed that despite the OS results favoring Dato-DXd numerically, the difference wasn't statistically significant across the entire trial population. However, in a particular subgroup of patients with non-squamous non-small cell lung cancer (NSCLC), Dato-DXd demonstrated a clinically meaningful improvement in OS.

Susan Galbraith, AstraZeneca’s Executive Vice President of Oncology R&D, expressed that despite the trial not meeting its primary endpoint, the data suggests the potential for Dato-DXd to replace conventional chemotherapy in late-line NSCLC. She added that the findings support ongoing trials exploring Dato-DXd’s effectiveness in first-line lung cancer treatments.

The TROPION-Lung01 study is a randomized, open-label trial including over 600 adults with advanced or metastatic NSCLC requiring systemic therapy after previous treatments. Dual primary endpoints for the trial are overall survival (OS) and progression-free survival (PFS). Key secondary outcomes include objective response rate (ORR), duration of response, and disease control rate.

During the European Society for Medical Oncology (ESMO) Congress in October 2023, AstraZeneca and Daiichi Sankyo presented progression-free survival (PFS) data from the TROPION-Lung01 trial. The data revealed that Dato-DXd reduced the risk of disease progression or death by 25% compared to docetaxel. Notably, the effect was more significant in the subset of patients with non-squamous NSCLC, where the risk reduction was 37%.

In addition to improved PFS, Dato-DXd also demonstrated superior objective response rate (ORR) and median duration of response compared to docetaxel.

Dato-DXd is currently under review by the U.S. Food and Drug Administration (FDA) for treating locally advanced or metastatic NSCLC. The Biologics License Application (BLA) was accepted by the FDA in February 2024, backed by data from the TROPION-Lung01 study. The target action date for the FDA’s decision is December 20, 2024.

Dato-DXd operates by targeting the TROP2 antigen, which is highly expressed in various cancers including breast, colorectal, gastric, and lung cancers. The ADC carries a topoisomerase I inhibitor payload, which promotes cancer cell death upon internalization and release within the cell. Additionally, Dato-DXd can initiate a bystander effect that destroys neighboring tumor cells.

Besides its application in lung cancer, Daiichi Sankyo and AstraZeneca are also exploring the potential of Dato-DXd in treating several types of breast cancer.