FDA Approves Trastuzumab Deruxtecan for HER2-Mutant NSCLC

The FDA has granted an accelerated approval to fam-trastuzumab deruxtecan-nxki for adult patients with unresectable or metastatic non–small cell lung cancer whose tumors have activating HER2 mutations, as detected by an FDA-approved test, and who have received previous systemic therapy.

Moreover, the Life Technologies Corporation’s Oncomine Dx Target Test and the Guardant360 CDx test have been greenlit for use as companion diagnostics for the antibody-drug conjugate. The FDA stated that if no mutation is detected in a plasma specimen, the tumor tissue should be tested.

Trastuzumab deruxtecan was examined at a dose of 6.4 mg/kg (n = 152) across several trials, as well as at a dose of 5.4 mg/kg (n = 102) in a randomized dose-finding trial. Response rates achieved with the agent proved to be consistent across the dose levels evaluated. However, increased rates of interstitial lung disease/pneumonitis were noted at the higher dose. The recommended dose of the agent is 5.4 mg/kg every 3 weeks.

The regulatory decision was supported by findings from the multicenter, multicohort, randomized, blinded, dose-optimization phase 2 DESTINY-Lung02 trial (NCT04644237). The trial enrolled patients with unresectable or metastatic, HER2-mutant, nonsquamous NSCLC who experienced disease progression following previous systemic therapy. Patients were selected for treatment with trastuzumab deruxtecan if an activating HER2 mutation was present in their tumor specimen.

Study participants were administered trastuzumab deruxtecan at 5.4 mg/kg every 3 weeks until progressive disease or intolerable toxicity.

A total of 52 patients comprised the primary efficacy population. The median age in these patients was 58 years (range, 30-78). Most patients were female (69%) and Asian (79%).

Confirmed objective response rate (ORR) per blinded independent central review and RECIST v1.1 criteria and duration of response (DOR) served as the major efficacy outcome measures for the trial.

Data showed that trastuzumab deruxtecan elicited a confirmed ORR of 58% (95% CI, 43%-71%) with a median DOR of 8.7 months (95% CI, 7.1–not estimable [NE]).

Regarding safety, the most common toxicities experienced by 20% or more of patients included decreased white blood cell count, hemoglobin, neutrophil count, lymphocyte count, platelet count, and albumin. Other common adverse effects included increased aspartate aminotransferase and alanine aminotransferase, as well as nausea, fatigue, constipation, decreased appetite, vomiting, increased alkaline phosphatase, and alopecia.

Reference

FDA grants accelerated approval to fam-trastuzumab deruxtecan-nxki for HER2-mutant non-small cell lung cancer. News release. FDA. August 11, 2022. Accessed August 11, 2022. https://bit.ly/3bVts9g