Patritumab Deruxtecan Shows Significant PFS Improvement Over Chemotherapy in EGFR-Mutated NSCLC Trial

The HERTHENA-Lung02 phase 3 clinical trial has demonstrated promising results in the treatment of patients with locally advanced or metastatic EGFR-mutated non-small cell lung cancer (NSCLC) who had previously been treated with EGFR tyrosine kinase inhibitors (TKIs). The study investigated the efficacy of patritumab deruxtecan, a HER3 directed DXd antibody-drug conjugate (ADC), compared to the standard regimen of platinum plus pemetrexed induction chemotherapy followed by pemetrexed maintenance therapy.

Patritumab deruxtecan, developed by Daiichi Sankyo in collaboration with Merck, showed a statistically significant improvement in progression-free survival (PFS), which was the primary endpoint of the study. Although overall survival (OS) data were not mature at the time of analysis, the trial will continue to assess this secondary endpoint. The NSCLC cases with EGFR mutations represent a significant portion of lung cancer diagnoses worldwide, with up to 38% of NSCLC tumors exhibiting these mutations. These patients often face limited treatment options after initial TKI therapy, emphasizing the need for new therapeutic approaches.

The HERTHENA-Lung02 trial enrolled 586 patients across multiple regions, including Asia, Europe, North America, and Oceania. Participants included those whose cancers had progressed after third-generation EGFR TKI treatments such as osimertinib, lazertinib, aumolertinib, and alflutinib. In the trial, patients were randomized to receive either patritumab deruxtecan or a combination of platinum chemotherapy and pemetrexed. Those in the comparator arm who did not show disease progression after the initial chemotherapy cycles could continue with pemetrexed maintenance therapy.

The study's secondary endpoints encompassed overall survival, objective response rate, duration of response, clinical benefit rate, time to response, disease control rate, and safety. The safety profile of patritumab deruxtecan was consistent with previous studies, with most interstitial lung disease (ILD) events being low grade. However, there were two reported cases of grade 5 ILD events.

Notably, NSCLC is the most prevalent form of lung cancer, accounting for about 85% of cases globally. With a high percentage of these cases diagnosed at an advanced stage, patients often require multiple lines of therapy. Unfortunately, the prognosis worsens with each subsequent treatment. EGFR mutations, found in a significant portion of these tumors, drive the need for effective treatments post-TKI therapy.

HER3, part of the HER receptor family, is implicated in poor outcomes for NSCLC patients, with high expression levels after prior EGFR TKI treatments. This receptor is linked to reduced survival rates and quicker relapse times. Currently, there are no approved HER3-targeted therapies for any type of cancer, making the results of the HERTHENA-Lung02 trial particularly noteworthy.

Patritumab deruxtecan is being tested in multiple clinical trials, both as a monotherapy and in combination with other treatments. These trials span various cancer types, including breast cancer, melanoma, gastric cancer, and head and neck cancer. The ongoing research efforts underscore the commitment of Daiichi Sankyo and Merck to developing innovative treatments for cancer patients with high unmet needs.

The collaboration between Daiichi Sankyo and Merck began in October 2023, focusing on the joint development and commercialization of ADCs, including patritumab deruxtecan. This partnership aims to advance the therapeutic landscape for patients with difficult-to-treat cancers, leveraging the strengths and expertise of both companies.