Pembrolizumab-Involved Phase 3 NSCLC Trial with HER2 Mutations Reaches Primary…

The Phase 3 study investigating pembrolizumab (Keytruda) for unresectable, locally advanced/metastatic non-small cell lung cancer (NSCLC) with HER2 mutations reached primary completion on 2026-04-30. This trial, known as DESTINY-Lung04, is evaluating trastuzumab deruxtecan against a standard of care that includes pembrolizumab as a first-line treatment.

Background

Pembrolizumab (Keytruda) is an established immunotherapy. The DESTINY-Lung04 trial focuses on locally advanced or metastatic non-small cell lung cancer (NSCLC) with HER2 Exon 19 or 20 mutations, a specific subset of lung cancer.

Trial design

The DESTINY-Lung04 study (NCT05048797) is a Phase 3, randomized trial with an enrollment of 454 participants. The trial is investigating treatments for locally advanced or metastatic non-small cell lung cancer with HER2 Exon 19 or 20 mutations. The study's brief summary indicates it will investigate the efficacy and safety of trastuzumab deruxtecan (T-DXd) versus Standard of Care (SoC) as first-line treatment. The interventions listed include trastuzumab deruxtecan, cisplatin, carboplatin, pembrolizumab, and pemetrexed, with pembrolizumab being part of the SoC arm.

What this means

The primary completion of the DESTINY-Lung04 trial signifies that the main data collection phase for the study has concluded. This milestone precedes the analysis of the collected data, which will evaluate the efficacy and safety of the investigated treatments, including the role of pembrolizumab within the standard of care arm for patients with unresectable, locally advanced or metastatic non-small cell lung cancer with HER2 mutations. Future announcements will detail the trial's outcomes.

Source

The information regarding the primary completion of this trial was obtained from ClinicalTrials.gov, a public database of clinical studies. The update for study NCT05048797, titled "A Study to Investigate the Efficacy and Safety of Trastuzumab Deruxtecan as the First Treatment Option for Unresectable, Locally Advanced/Metastatic Non-Small Cell Lung Cancer With HER2 Mutations," was posted on 2026-04-30 on clinicaltrials.gov.