Patritumab Deruxtecan for Patients With Previously Treated, EGFR-Mutated Non-Small Cell Lung Cancer

Results from the phase 2 HERTHENA-Lung01 trial found that patritumab deruxtecan is a clinically durable and effective treatment option for patients with EGFR-mutated non-small cell lung cancer (NSCLC) who have experienced disease progression after treatment with platinum-based chemotherapy or an EGFR tyrosine kinase inhibitor (TKI). 

According to previous phase 1 data, “[patritumab deruxtecan] once every 3 weeks was effective in patients with diverse mechanisms of resistance to EGFR TKIs, including EGFR-dependent and -independent mechanisms,” stated Helena A. Yu, MD, Memorial Sloan Kettering Cancer Center, New York, New York, and coauthors. In the present trial, “we assessed the efficacy and safety of [patritumab deruxtecan] in patients with [EGFR]-mutated [NSCLC].”

In this multicenter, open-label study, patients who experienced disease progression on or after treatment with ≥1 line of EGFR TKI or ≥1 line of platinum-based chemotherapy were enrolled into study arms to receive intravenous patritumab deruxtecan once every 3 weeks in a fixed-dose or uptitration regimen. After trial initiation, enrollment into the uptitration arm closed early due to benefit-risk results from a phase 1 trial. Additionally, eligibility was extended to patients with clinically inactive or treated brain metastases who were asymptomatic and had previously been treated with osimertinib. The primary end point was objective response rate (ORR) confirmed by blinded independent central review (BICR). Secondary end points included duration of response (DOR), progression-free survival (PFS), overall survival (OS), and safety. 

At the data cutoff point, 225 patients were treated with 5.6 mg/kg of patritumab deruxtecan intravenously every 3 weeks and the median study duration was 18.9 months. Confirmed ORR by BICR was 29.8%, median DOR was 6.4 months, median PFS was 5.5 months, and median OS was 11.9 months. In a subgroup of patients previously treated with osimertinib and platinum-based chemotherapy outcomes were similar. Additionally, efficacy was observed among patients with a broad range of pretreatment tumor HER3 membrane expression levels and across diverse mechanisms of EGFR TKI resistance. Among patients with nonirrigated brain metastases at baseline, the confirmed CNS ORR was 33.3%. The safety profile was manageable and tolerable as consistent with previous study results. 

“After tumor progression with EGFR TKI therapy and [platinum-based chemotherapy] in patients with EGFR-mutated NSCLC, [patritumab deruxtecan] once every 3 weeks demonstrated clinically meaningful efficacy with durable responses, including in CNS metastases,” concluded Dr Yu and coauthors. 

“Antibody drug conjugates have a novel mechanism of action and may become standard therapies in the treatment of NSCLC in the future,” added associate editor of Journal of Clinical Oncology, Thomas E. Stinchcombe, MD, Duke Cancer Center, Durham, North Carolina.

Source:

Yu HA, Goto Y, Hayashi H, et al. HERTHENA-lung01, a phase 2 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. J Clin Oncol. Published online: September 10, 2023. doi: 10.1200/JCO.23.01476