FDA Grants Breakthrough Designation to Trastuzumab Deruxtecan for HER2+ mNSCLC

The FDA has granted a breakthrough therapy designation to fam-trastuzumab deruxtecan-nxki (Enhertu) for the treatment of patients with HER2-mutant metastatic non–small cell lung cancer (mNSCLC) who have progressed on or after treatment with a platinum-based chemotherapy regimen, according to a press release from AstraZeneca and Daiichi Sankyo.¹

“Today’s news is very welcome as we continue to evaluate the potential of Enhertu to help patients with this devastating type of lung cancer. Targeted treatments and immunotherapies are demonstrating tremendous advancements, but there remains an unmet medical need for patients with HER2 mutations who are not benefiting from such therapies or for those whose cancer continues to progress,” said José Baselga, MD, PhD, executive vice president, Research & Development Oncology, AstraZeneca, in the press release.

The breakthrough designation was granted as a result of data from the ongoing phase II DESTINY-Lung01 trial and from the completed phase I trial.

DESTINY-Lung01 is a global, open-label, multicenter phase II trial that is exploring the safety and efficacy of trastuzumab deruxtecan in patients with HER2-mutant or HER2-overexpressing unresectable and metastatic nonsquamous NSCLC. In the study, eligible patients are those who have progressed after ≥1 systemic regimen—including chemotherapy, targeted therapy, or immunotherapy—and have HER2 expressed defined as IHC 2+ or 3+. The study is divided into 2 cohorts, one for patients with HER2 mutations (n = 90), and the second for patients with HER2 overexpression.

The study’s primary end point is objective response rate (ORR) and key secondary outcome measures include duration of response, disease control rate, progression-free survival (PFS), and overall survival.

An interim analysis of the study’s findings will be presented at the 2020 American Society of Clinical Oncology (ASCO20) Virtual Scientific Program.

Findings from the phase I dose-expansion trial of trastuzumab deruxtecan in patients with advanced solid tumors showed significant activity in patients with HER2-mutant NSCLC.²

In this patient population (n = 11), the ORR was 72.7% and the median PFS was 11.3 months (95% CI, 8.1-14.3).

According to the press release, as of the interim data cutoff, safety was investigated in 42 patients in the DESTINY-Lung01 trial and is consistent with reports from the phase I trial. The most common adverse events reported were nausea, alopecia, anemia, decreased appetite, and decreased neutrophil count. Five cases of grade 2 drug-related interstitial lung disease and pneumonitis have been reported, but there have not been any interstitial lung disease–related deaths.¹

“We are encouraged by the promising evidence of activity seen with Enhertu in patients with advanced lung cancer and a HER2 mutation. We look forward to working closely with the FDA on the potential for Enhertu to become the first HER2-directed therapy approved for non-small cell lung cancer,” Gilles Gallant, senior vice president, global head, Oncology Development, Oncology R&D, Daiichi Sankyo, said in the press release.

This marks the third breakthrough therapy designation granted to the HER2-targeted antibody-drug conjugate by the FDA. The agent is FDA-approved for the treatment of adult patients with unresectable or metastatic HER2-positive metastatic breast cancer who have received ≥2 prior anti-HER2–based regimens.

References:

_{1. ENHERTU Granted Breakthrough Therapy Designation in the US for HER2-Mutant Metastatic Non-Small Cell Lung Cancer [news release]. Wilmington, DE: AstraZeneca and Daiichi Sankyo Company, Limited; May 18, 2020. https://bwnews.pr/2X5scoU. Accessed May 18, 2020.}

_{2. Tsurutani J, Iwata H, Krop I, et al. Targeting her2 with trastuzumab deruxtecan: a dose-expansion, phase I study in multiple advanced solid tumors [Published online March 25, 2020]. Cancer Discov. doi: 10.1158/2159-8290.CD-19-1014}