Phase II DESTINYLung01 trial positive for Enhertu/Enhurtu in HER2 mutant NSCLC.- Daiichi Sankyo and AstraZeneca.

Results from the ongoing phase II DESTINYLung01 trial showed Daiichi Sankyo Company, Limited and AstraZeneca’s Enhertu (fam-trastuzumab deruxtecan-nxki) achieved a clinically meaningful tumor response in patients with HER2 mutant unresectable and/or metastatic non-squamous non-small cell lung cancer (NSCLC) whose disease had progressed following one or more systemic therapies. These results were presented at the 2020 American Society of Clinical Oncology Virtual Scientific Program (#ASCO20).

Lung cancer is the leading cause of cancer death among both men and women, and accounts for about one fifth of all cancer deaths, with 80 to 85 percent classified as NSCLC. There are currently no medicines approved specifically for the treatment HER2 mutant NSCLC, which affects approximately two to four percent of patients with NSCLC.

The primary endpoint of confirmed objective response rate (ORR), also called a tumor response rate, which was assessed by independent central review (ICR), was 61.9% for patients treated with Enhertu monotherapy (6.4 mg/kg). Patients achieved a disease control rate (DCR) of 90.5% with a median progression free survival (PFS) of 14.0 months. Median duration of response (DoR) and overall survival (OS) had not yet been reached at the time of data cut-off. The overall safety and tolerability profile of Enhertu in DESTINY-Lung01 was consistent with that seen in the phase 1 trial and previously reported Enhertu trials. The most common grade 3 or higher treatment emergent adverse events were decreased neutrophil count (26.2%) and anemia (16.7%). There were five cases (11.9%) of confirmed treatment-related interstitial lung disease (ILD) and pneumonitis as determined by an independent adjudication committee. All ILD and pneumonitis were grade 2. One grade 1 ILD is still undergoing adjudication.

Comment: Daiichi Sankyo and AstraZeneca are positioning Enhertu as a therapy for patients with HER2-mutated NSCLC who have previously been treated with PD-1/PD-L1 inhibitors, an area of great unmet need for these patients who have few, if any, treatment options left.