Merck and Daiichi Achieve Late-Stage NSCLC Success for ADC Despite Two Deaths

Despite achieving the primary endpoint in a Phase III study, two individuals treated with the experimental drug patritumab deruxtecan, developed by Merck and Daiichi Sankyo, died during a trial for non-small cell lung cancer (NSCLC). These fatalities were not attributed to the drug itself.

On Tuesday, Merck and Daiichi Sankyo announced that their investigational antibody-drug conjugate (ADC) patritumab deruxtecan met the primary endpoint in the Phase III HERTHENA-Lung02 study focused on NSCLC. This study’s results were consistent with previous research, showing no new safety concerns. While most cases of interstitial lung disease (ILD) observed were low grade, there were two lethal cases (grade 5 ILD), but no direct causal link to the drug was identified.

Though detailed data from the HERTHENA-Lung02 study was not disclosed, Merck and Daiichi Sankyo mentioned that patritumab deruxtecan demonstrated a statistically significant improvement in progression-free survival compared to the standard platinum plus pemetrexed induction chemotherapy followed by pemetrexed maintenance. However, at the time of the interim analysis, data on overall survival were not yet conclusive, and the study will continue monitoring participants.

HERTHENA-Lung02 is an open-label, late-stage trial involving patients with locally advanced or metastatic NSCLC who have EGFR mutations and have previously been treated with an EGFR tyrosine kinase inhibitor. Merck and Daiichi Sankyo plan to present the full findings from this study at an upcoming medical conference and will share the results with regulatory authorities to discuss the next steps.

Ken Takeshita, global head of R&D at Daiichi Sankyo, commented on the significance of the study’s results, stating that they demonstrate the potential of patritumab deruxtecan to become an important treatment option for certain patients with EGFR-mutated NSCLC who have had prior tyrosine kinase inhibitor treatment.

Patritumab deruxtecan is an antibody-drug conjugate composed of a fully human IgG1 monoclonal antibody targeting the HER3 protein on cancer cells, paired with an exatecan derivative payload, which is a topoisomerase I inhibitor that can induce cell death. This ADC is a key element of the $22 billion agreement between Merck and Daiichi Sankyo made in October 2023, granting Merck the rights to co-develop and co-commercialize three investigational ADCs for cancer treatment.

In the Phase II HERTHENA-Lung01 study, patritumab deruxtecan showed an overall response rate of nearly 30% in patients with EGFR-mutated locally advanced or metastatic NSCLC, including one complete response and 66 partial responses. The median duration of response at that time was over six months. However, in June 2024, the FDA denied approval for patritumab deruxtecan due to issues with a third-party manufacturing facility, although the ADC’s safety and efficacy data were not questioned.

The announcement regarding HERTHENA-Lung02 comes shortly after the 2024 World Congress on Lung Cancer, where Daiichi Sankyo presented less favorable Phase III data for a different ADC, datopotamab deruxtecan (Dato-DXd), partnered with AstraZeneca. In the late-stage TROPION-Lung01 study, Dato-DXd reduced the risk of death by only 6%, falling short of statistical significance. Its overall survival benefit in the non-squamous population was also not statistically significant. Despite this, Daiichi Sankyo and AstraZeneca are still seeking approval for Dato-DXd in non-squamous NSCLC, with a target action date set for December 20, 2024.