Trastuzumab Deruxtecan Granted Priority Review by FDA for Previously Treated HER2-Mutant Metastatic NSCLC

Patients with HER2-mutated metastatic non–small cell lung cancer who have previously received treatment with systemic therapies appear to benefit from treatment with fam-trastuzumab deruxtecan-nxki, which received priority review from the FDA.

The FDA has accepted a supplemental biologics license application for and granted priority review to fam-trastuzumab deruxtecan-nxki (Enhertu) for the treatment of patients with HER2-mutated metastatic non–small cell lung (NSCLC) cancer following treatment with prior systemic therapy, according to a press release from AstraZeneca and Daiichi Sankyo.1

The designation is built on findings from the phase 2 DESTINY-Lung01 trial (NCT03505710), in which investigators identified an objective response rate of 54.9% (95% CI, 44.2%-65.4%) among those treated with a 6.4 mg/kg dose of trastuzumab deruxtecan. Forty-nine patients (53.8%) achieved a partial response and 1 (1.1%) achieved a complete response.

If approved, the HER2-directed antibody-drug conjugate could offer significant improvement over other therapeutics, as demonstrated by promising safety and efficacy findings. The prescription drug user free act date is set for the third quarter of 2022.

“The DESTINY-Lung01 trial confirmed the HER2 mutation as an actionable biomarker in non–small cell lung cancer. If approved, [trastuzumab deruxtecan] has the potential to become a new standard treatment in this patient population, offering a much-needed option for patients with HER2-mutant metastatic non–small cell lung cancer who currently have no targeted treatment options,” according to Susan Galbraith, executive vice president of Oncology R&D at AstraZeneca.

Additional findings from the study included a confirmed disease control rate of 92.3%, as well as an observable reduction in tumor size in the majority of patients. The median duration of response was 9.3 months after a median follow-up of 13.1 months. Additionally, the median progression-free survival and overall survival were 8.2 months and 17.8 months, respectively.

Trastuzumab deruxtecan received a breakthrough therapy designation in May 2020 for patients with HER2-mutated metastatic NSCLC who have experienced progression on or following a platinum-based regimen.2

“The results of DESTINY-Lung01 showed that [trastuzumab deruxtecan] is the first HER2-directed therapy to demonstrate a strong and robust tumor response in more than half of patients with previously treated HER2-mutant metastatic [NSCLC]. Seeking approval in the US for a third tumor type in 3 years further demonstrates the significant potential of [trastuzumab deruxtecan] in treating multiple HER2-targetable cancers,” Ken Takeshita, MD, global head of R&D at Daiichi Sankyo, concluded.

References

  1. Enhertu granted priority review in the US for patients with previously treated HER2-mutant metastatic non-small cell lung cancer. News release. AstraZeneca and Daiichi Sankyo. April 19, 2022. Accessed April 19, 2022. https://bit.ly/3KZhqIv
  2. Enhertu granted breakthrough therapy designation in the US for HER2-mutant metastatic non-small cell lung cancer. News release. AstraZeneca and Daiichi Sankyo. May 18, 2020. Accessed April 19, 2022. https://bit.ly/3xC5wjI