Rejected HER3 ADC by Merck and Daiichi succeeds in Phase 3 for specific lung cancers

Merck and Daiichi Sankyo have achieved a significant milestone in their joint venture with their lead antibody-drug conjugate (ADC), patritumab deruxtecan. The results were revealed as the European Society for Medical Oncology (ESMO) conference concluded, demonstrating promising outcomes from their Phase 3 clinical trial, labeled HERTHENA-Lung02. This follows a setback earlier this year when the U.S. Food and Drug Administration (FDA) rejected the drug due to manufacturing issues.

The HERTHENA-Lung02 trial focused on patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with EGFR mutations, who had previously been treated with an EGFR tyrosine kinase inhibitor. The study aimed to compare the efficacy of patritumab deruxtecan against the current standard doublet chemotherapy. The new ADC demonstrated a statistically significant improvement in progression-free survival, meaning it was effective in prolonging the time patients lived without their disease worsening. However, the exact margin of this benefit was not disclosed.

The companies are now preparing to engage in regulatory discussions based on these promising results, as confirmed by a spokesperson from Merck. This step is crucial as they seek to navigate the complexities of drug approval following the FDA's earlier rejection over production concerns at a third-party manufacturing site.

Despite the positive progression-free survival data, the information concerning the secondary endpoint, overall survival, remains incomplete according to the companies. As overall survival is becoming increasingly critical for the FDA's evaluations, Merck and Daiichi Sankyo plan to continue the study to gather more comprehensive data on this measure.

In the trial, there were two reported deaths due to interstitial lung disease (ILD), a known risk associated with some cancer therapies. Most ILD events observed were of lower severity, classified as grades 1 and 2. This indicates that while there are serious risks associated with the treatment, these events are relatively rare and mostly manageable.

Merck and Daiichi Sankyo's collaboration extends beyond patritumab deruxtecan. They are also developing two other ADCs and have recently joined forces on a T cell engager acquired by Merck through its acquisition of Harpoon Therapeutics. Eliav Barr, Merck's chief medical officer, expressed optimism about the potential of these therapies to significantly impact the treatment landscape for small cell lung cancer, aiming to achieve transformative outcomes in this challenging area of oncology.

The recent progress with patritumab deruxtecan marks a hopeful turn for the Merck-Daiichi partnership, especially after the earlier FDA setback. As they move forward with regulatory discussions, the focus will be on addressing any remaining concerns and continuing to gather robust data to support the safety and efficacy of their innovative therapies. The oncology community will be watching closely as these developments unfold, hopeful for new advancements in the treatment of lung cancer.