The Food and Drug Administration (FDA) has granted Priority Review to fam-trastuzumab deruxtecan-nxki (Enhertu®; Daiichi Sankyo) for the treatment of patients with HER2-positive metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma.

The supplemental Biologics License Application includes data from the open-label, randomized phase 2 DESTINY-Gatric01 trial that compared the efficacy and safety of fam-trastuzumab deruxtecan-nxki, an HER2-directed antibody and topoisomerase inhibitor conjugate, to chemotherapy in 187 patients with HER2-positive advanced gastric or GEJ cancer who had progressed from 2 prior therapies including trastuzumab. Patients were randomized 2:1 to receive fam-trastuzumab deruxtecan-nxki (n=125) or physician’s choice of chemotherapy (n=62). 

The primary end point was the objective response rate (ORR), according to an independent central review based on RECIST v1.1. The key secondary end point included overall survival.

Results from the study showed an ORR of 51% with fam-trastuzumab deruxtecan-nxki vs 14% for chemotherapy (P <.001). Moreover, treatment with fam-trastuzumab deruxtecan-nxki was associated with a significant improvement in overall survival compared with chemotherapy (12.5 months vs 8.4 months, respectively; hazard ratio for death, 0.59; 95% CI, 0.39-0.88; P =.01).

As for safety, the most common adverse events of grade 3 or higher for fam-trastuzumab deruxtecan-nxki vs chemotherapy were decreased neutrophil count (51% vs 24%), anemia (38% vs 23%), and decreased white cell count (21% vs 11%), respectively. There was 1 drug-related death due to pneumonia in the fam-trastuzumab deruxtecan-nxki arm compared with no drug-related deaths in the chemotherapy arm.

“The results of the DESTINY-Gastric01 trial are unprecedented as they represent the first time an HER2-directed medicine has demonstrated an improvement in survival following chemotherapy and HER2 treatment in the metastatic setting,” said Antoine Yver, Executive VP and Global Head, Oncology Research and Development, Daiichi Sankyo.

The FDA previously granted Breakthrough Therapy and Orphan Drug designations to fam-trastuzumab deruxtecan-nxki for this indication. A Prescription Drug User Fee Act (PDUFA) date for the first quarter of 2021 has been set for this application.

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Fam-trastuzumab deruxtecan-nxki is marketed under the brand name Enhertu and is currently approved for the treatment of patients with unresectable or metastatic HER2-positive breast cancer who have received at least 2 prior anti-HER2-based regiments in the metastatic setting. 

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  1. Enhertu (fam-trastuzumab deruxtecan-nxki) granted Priority Review in the US For the treatment of HER2-positive metastatic gastric cancer. [press release]. Wilmington, DE: AstraZeneca and Daiichi Sankyo; October 28, 2020. 
  2. Shitara K, Bang YJ, Iwasa S, et al. Trastuzumab deruxtecan in previously treated HER2-positive gastric cancer. N Engl J Med. Published online June 18, 2020. doi: 10.1056/NEJMoa2004413.