FDA grants Enhertu accelerated approval for HER2-mutated non-small cell lung cancer
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The FDA granted accelerated approval to fam-trastuzumab deruxtecan-nxki for treatment of adults with HER2-mutated unresectable or metastatic non-small cell lung cancer.
The approval applies to patients with activating HER2 (ERBB2) mutations detected by an FDA-approved test who received a prior systemic therapy.
Fam-trastuzumab deruxtecan (Enhertu; AstraZeneca, Daiichi Sankyo) is a novel antibody-drug conjugate with three components: a humanized anti-HER2 immunoglobulin G1 monoclonal antibody with the same amino acid sequence as trastuzumab (Herceptin, Genentech); a topoisomerase 1 inhibitor payload; and a tetrapeptide-based cleavable linker. It is the first drug to receive FDA approval for HER2-mutant NSCLC, according to an FDA press release.
The FDA based the accelerated approval on results of the randomized, multicenter phase 2 DESTINY-Lung02 trial, which enrolled 152 patients with HER2-mutant metastatic NSCLC who experienced disease recurrence or progression during or following at least one prior anticancer therapy regimen that contained a platinum-based chemotherapy.
The trial’s primary efficacy population included 52 patients (median age, 58 years; 69% women; 79% Asian) who received fam-trastuzumab deruxtecan at a dose of 5.4 mg/kg via IV every 3 weeks until disease progression or unacceptable toxicity.
Major efficacy outcomes included confirmed objective response rate per blinded independent central review and duration of response.
Results of an interim efficacy analysis showed a confirmed ORR of 57.7% (95% CI, 43.2-71.3) and median duration of response of 8.7 months (95% CI, 7.1 to not estimable).
The most common adverse events included nausea, decreased white blood cell count, increased aspartate aminotransferase, increased alanine aminotransferase, fatigue, constipation, decreased appetite, vomiting, increased alkaline phosphatase and alopecia.
The prescribing information includes a boxed warning about risk for interstitial lung disease and embryo-fetal toxicity.
“The approval of trastuzumab deruxtecan in non-small cell lung cancer is an important milestone for patients and the oncology community,” Bob T. Li, MD, PhD, MPH, medical oncologist and physician-scientist at Memorial Sloan Kettering Cancer Center, said in a company press release. “After 2 decades of research into the role of targeting HER2 in lung cancer, the approval of the first HER2-directed treatment option validates HER2 as an actionable target in lung cancer and marks an important step forward for treating this patient population with unmet medical needs.”
Results of DESTINY-Lung02 will be presented at a future medical meeting, according to the company press release.
FDA also approved two companion diagnostics for fam-trastuzumab deruxtecan — Oncomine Dx Target Test (Life Technologies Corp.) for tissue and Guardant360 CDx (Guardant Health Inc.) for plasma. If a mutation is not detected in a plasma specimen, the tumor tissue should be tested, according to the FDA press release.
Fam-trastuzumab deruxtecan already had been approved in the United States for treatment of adults with metastatic HER2-positive breast cancer who received prior anti-HER2-based therapies, as well as adults with HER2-positive advanced gastric or gastroesophageal junction adenocarcinoma who received a prior trastuzumab-based regimen. Last week, the FDA approved the agent for treatment patients with unresectable or metastatic HER2-low breast cancer who received prior chemotherapy in the metastatic setting or whose disease progressed during or within 6 months of adjuvant chemotherapy.
References:
Enhertu approved in the U.S. as the first HER2 directed therapy for patients with previously treated HER2 mutant metastatic non-small cell lung cancer (press release). Available at: www.businesswire.com/news/home/20220811005803/en/ENHERTU%C2%AE-Approved-in-the-U.S.-as-the-First-HER2-Directed-Therapy-for-Patients-with-Previously-Treated-HER2-Mutant-Metastatic-Non-Small-Cell-Lung-Cancer. Published Aug. 11, 2022. Accessed Aug. 11, 2022.
FDA grants accelerated approval to fam-trastuzumab deruxtecan-nxki for HER2-mutant non-small cell lung cancer (press release). Available at: www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-fam-trastuzumab-deruxtecan-nxki-her2-mutant-non-small-cell-lung?utm_medium=email&utm_source=govdelivery. Published Aug. 11, 2022. Accessed Aug. 11, 2022.
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