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Daiichi Sankyo, AstraZeneca Begin Phase III Trial of Enhertu in HER2-Mutant NSCLC

*December 2021*

NEW YORK – Daiichi Sankyo and AstraZeneca on Thursday said that the first patient with HER2-mutant advanced non-small cell lung cancer has received treatment in a Phase III trial comparing their antibody-drug conjugate trastuzumab deruxtecan (Enhertu) against an immunotherapy-chemotherapy combination in the first-line setting.

The DESTINY-Lung04 trial is evaluating trastuzumab deruxtecan against standard-of-care platinum-pemetrexed doublet chemotherapy plus the checkpoint inhibitor pembrolizumab (Merck’s Keytruda) in around 260 patients with unresectable, locally advanced, or metastatic NSCLC harboring HER2 exon 19 or 20 mutations.

The primary endpoint of the study is progression-free survival. Researchers will also measure overall survival, overall response rate, duration of response, pharmacokinetics, and patient-reported tolerability, immunogenicity, and safety.

AstraZeneca and Daiichi Sankyo are launching the Phase III trial after seeing that trastuzumab deruxtecan had encouraging activity in HER2-mutated, previously treated, advanced NSCLC patients in the Phase II DESTINY-Lung01 trial. In that study, 55 percent of patients responded to the drug; median progression-free and overall survival was 8.2 months and 17.8 months, respectively.

“The results seen in the DESTINY-Lung01 trial showed a robust and durable tumor response in previously-treated patients with HER2-mutant metastatic non-small cell lung cancer,” Gilles Gallant, senior VP and global head of oncology development at Daiichi Sankyo, said in a statement. “Based on these promising findings, we are conducting DESTINY-Lung04 to evaluate the potential of Enhertu as an earlier line of therapy in this patient population.”

Trastuzumab deruxtecan is already available in the US as a third-line treatment for metastatic HER2-positive breast cancer and for advanced HER2-positive gastric cancer patients who have received other regimens containing trastuzumab (Genentech’s Herceptin). AstraZeneca and Daiichi Sankyo are also studying trastuzumab deruxtecan in other HER2-positive breast, gastric, and colorectal cancer indications. Read more.