FDA grants accelerated approval to fam-trastuzumab deruxtecan-nxki for HER2-mutant non-small cell lung cancer

12 Aug 2022
FDA grants accelerated approval to fam-trastuzumab deruxtecan-nxki for HER2-mutant non-small cell lung cancer

On August 11, 2022, the Food and Drug Administration granted accelerated approval to fam-trastuzumab deruxtecan-nxki for adult patients with unresectable or metastatic non-small cell lung cancer (NSCLC) whose tumours have activating human epidermal growth factor receptor 2 HER2 (ERBB2) mutations, as detected by an FDA-approved test, and who have received prior systemic therapy. This is the first drug approved for HER2-mutant NSCLC.

FDA also approved the Life Technologies Corporation’s Oncomine™ Dx Target Test (tissue) and the Guardant Health, Inc.’s Guardant360® CDx (plasma) as companion diagnostics for fam-trastuzumab deruxtecan-nxki. If no mutation is detected in a plasma specimen, the tumour tissue should be tested.

Fam-trastuzumab deruxtecan-nxki was evaluated at a 6.4 mg/kg dose (n=152) across multiple trials and at a 5.4 mg/kg dose (n=102) in a randomized dose-finding trial. Response rates were consistent across dose levels. Increased rates of interstitial lung disease/pneumonitis were observed at the higher dose. The efficacy results of the approved recommended dose of 5.4 mg/kg given intravenously every 3 weeks are described below.

Efficacy for accelerated approval was based on DESTINY-Lung02, a multicenter, multi-cohort, randomized, blinded, dose-optimisation trial. Eligible patients were required to have unresectable or metastatic HER2-mutant non-squamous NSCLC with disease progression after prior systemic therapy.

Patients were selected for treatment with fam-trastuzumab deruxtecan-nxki based on the presence of activating HER2 (ERBB2) mutations in a tumour specimen. Patients received fam-trastuzumab deruxtecan-nxki 5.4 mg/kg by intravenous infusion, every 3 weeks until unacceptable toxicity or disease progression.

Of the 52 patients in the primary efficacy population DESTINY-Lung02, the median age was 58 years (range 30 to 78), 69% were female; 79% were Asian, 12% were White, and 10% were of other races. The major efficacy outcome measures were confirmed objective response rate (ORR) as assessed by blinded independent central review using RECIST v1.1 and duration of response (DOR). The confirmed ORR was 58% (95% CI: 43, 71) and the median DOR was 8.7 months (95% CI: 7.1, not estimable [NE]).

The most common (≥20%) adverse reactions, including laboratory abnormalities, were nausea, decreased white blood cell count, decreased haemoglobin, decreased neutrophil count, decreased lymphocyte count, decreased platelet count, decreased albumin, increased aspartate aminotransferase, increased alanine aminotransferase, fatigue, constipation, decreased appetite, vomiting, increased alkaline phosphatase, and alopecia. The prescribing information includes a Boxed Warning advising health professionals of the risk of interstitial lung disease and embryo-fetal toxicity.

View full prescribing information for fam-trastuzumab deruxtecan-nxki here.

Source: FDA