The following is a summary of “HERTHENA-Lung01, a Phase II Trial of Patritumab Deruxtecan (HER3-DXd) in Epidermal Growth Factor Receptor–Mutated Non–Small-Cell Lung Cancer After Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor Therapy and Platinum-Based Chemotherapy,” published in the December 2023 issue of Oncology by Yu, et al.

For a study, researchers sought to evaluate the efficacy and safety of HER3-DXd, an antibody-drug conjugate comprising a fully human monoclonal antibody targeting human epidermal growth factor receptor 3 (HER3) and a topoisomerase I inhibitor payload, in patients with advanced non-small-cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) mutations.

The phase II trial enrolled patients with EGFR-mutated NSCLC who had previously undergone EGFR tyrosine kinase inhibitor (TKI) therapy and platinum-based chemotherapy. Participants received HER3-DXd at 5.6 mg/kg intravenously every 3 weeks, with an up-titration regimen in some cases (3.2 → 4.8 → 6.4 mg/kg). The primary endpoint was the confirmed objective response rate (ORR) assessed by a blinded independent central review (BICR) with a null hypothesis based on historical data.

Enrollment into the up-titration arm was prematurely closed based on a prespecified benefit-risk assessment derived from the phase I U31402-A-U102 trial. A total of 225 patients were administered HER3-DXd at a dose of 5.6 mg/kg once every 3 weeks. As of May 18, 2023, the median study duration reached 18.9 months (range 14.9-27.5). The confirmed objective response rate (ORR) evaluated by blinded independent central review (BICR) was 29.8% (95% CI, 23.9 to 36.2). The median duration of response was 6.4 months, while progression-free survival and overall survival were 5.5 months and 11.9 months, respectively. Similar outcomes were observed in the subgroup of patients with prior exposure to osimertinib and platinum-based chemotherapy. Notably, efficacy was evident across a diverse spectrum of pretreatment tumor HER3 membrane expression levels and various EGFR tyrosine kinase inhibitor (TKI) resistance mechanisms. In the subset of patients with nonirradiated brain metastases at baseline (n = 30), the confirmed central nervous system (CNS) ORR by BICR per CNS RECIST stood at 33.3% (95% CI, 17.3 to 52.8). As assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events v5.0, the safety profile demonstrated manageability and tolerability, aligning with prior observations.

HER3-DXd demonstrated clinically meaningful efficacy with a confirmed ORR of 29.8%, durable responses, and manageable safety in patients with EGFR-mutated NSCLC following disease progression with EGFR TKI therapy and platinum-based chemotherapy. The findings suggested the potential of HER3-DXd as a promising therapeutic option for this patient population.

Source: ascopubs.org/doi/full/10.1200/JCO.23.01476