FDA Grants Priority Review to sBLA for Trastuzumab Deruxtecan for HER2+ Metastatic Gastric/GEJ Adenocarcinoma

The FDA granted a Priority Review designation to the supplemental Biologics License Application for trastuzumab deruxtecan as treatment of patients with HER2-positive metastatic gastric or gastroesophageal junction adenocarcinoma.

The FDA has granted a Priority Review designation to the supplemental Biologics License Application (sBLA) for trastuzumab deruxtecan (Enhertu) as treatment of patients with HER2-positive metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma, announced AstraZeneca in a press release.1

The Prescription Drug User Fee Act action date will be during the first quarter of 2021. The sBLA is supported by data from the randomized phase 2 DESTINY-Gastric01 clinical trial, which demonstrated a statistically significant and clinically meaningful improvement in both the objective response rate (ORR), meeting the primary end point of the study. The overall survival (OS), which was a key secondary end point, was also improved with trastuzumab deruxtecan compared with chemotherapy alone.

“Once patients with HER2-positive metastatic gastric cancer progress following initial treatment with an anti-HER2 regimen, there are no approved HER2-directed medicines,” José Baselga, executive vice president, Oncology Research and Development, stated. “The prognosis for these patients is poor, as available treatment options offer only limited clinical benefit. This milestone brings us one step closer to delivering a potentially practice-changing medicine to patients with gastric cancer in the US.”

The results from the DESTINY-Gastric01 study were presented during the 2020 American Society of Clinical Oncology Virtual Scientific Program and simultaneously published in The New England Journal of Medicine.The open-label multicenter study evaluated the efficacy and safety of trastuzumab deruxtecan as treatment of patients with HER2-expressing advanced gastric or GEJ adenocarcinoma who have received at least 2 prior lines of therapy, including fluoropyrimidine, a platinum-based agent, and trastuzumab or an approved biosimilar compared with the physician’s choice of standard chemotherapy, either paclitaxel or irinotecan monotherapy.2

The ORR by Independent Central Review (ICR) was significantly higher with the anti-HER2 antibody-drug conjugate (ADC), in which the ORR was 51.3% in the experimental arm (95% CI, 41.9%-60.5%; P <.0001) compared with 14.3% in the control arm (95% CI, 6.4%-26.2%). The complete response rate in the trastuzumab deruxtecan arm was 8.4% compared with no complete responses in the chemotherapy arm.

Additionally, the confirmed ORR by ICR was 42.9% (95% CI, 33.8-91.5) with the ADC versus 12.5% (95% CI, 5.2-24.1), and the confirmed disease control rate was 85.7% (95% CI, 78.1-91.5) versus 62.5% (95% CI, 48.5-75.1), respectively. The median duration of response with trastuzumab deruxtecan was 11.3 months (95% CI, 5.6-not evaluable [NE]) compared with 3.9 months with chemotherapy (95% CI, 3.0-4.9).

The median OS was 12.5 months (95% CI, 9.6-14.3) with the ADC versus 8.4 (95% CI, 6.9-10.7) with chemotherapy (HR, 0.59; 95% CI, 0.39-0.88; P =.0097), and the 1-year OS rates were 52.1% versus 28.9%, respectively. The 6-month OS rates were 80.3% with trastuzumab deruxtecan and 66.4% with chemotherapy.

The median progression-free survival (PFS) was 5.6 months (95% CI, 4.3-6.9) with trastuzumab deruxtecan versus 3.5 months (95% CI, 2.0-4.3) with chemotherapy (HR, 0.47; 95% CI, 0.31-0.71). The 6-month and 1-year PFS rates were 42.8% and 29.9% with the ADC versus 20.6% and 0% with physician’s choice, respectively.

The most common grade 3 or higher adverse events (AEs) with trastuzumab deruxtecan included neutropenia, decreased appetite, anemia, thrombocytopenia, and decreased white blood cell count. Treatment-emergent AEs that were associated with treatment discontinuation occurred in 15.2% of patients receiving the ADC versus 6.5% with chemotherapy, and events linked with dose reductions occurred in 32.0% of patients versus 33.9%, while events leading to dose interruptions were observed in 62.4% versus 37.1%, respectively.

“The results of the DESTINY-Gastric01 trial are unprecedented as they represent the first time a HER2-directed medicine has demonstrated an improvement in survival following chemotherapy and HER2 treatment in the metastatic setting,” said Antoine Yver, Executive Vice President and Global Head, Oncology Research and Development, Daiichi Sankyo, in a statement.1 “Building on the recent Breakthrough Therapy Designation, the filing of the application and Priority Review by the FDA for this potential new indication for Enhertu reflects the importance of the data and the significant unmet need for patients with previously treated HER2-positive metastatic gastric cancer.”


1. Enherty granted Priority Review in the US for the treatment of HER2-positive metastatic gastric cancer. News Release. AstraZeneca. October 28, 2020. Accessed October 28, 2020. https://bit.ly/3e53vkl

2. Siena S, Bartolomeo MD, Raghav K, et al. A phase 2, multicenter, open-label study of trastuzumab deruxtecan (T-DXd; DS-8201) in patients with HER2-expressing metastatic colorectal cancer: DESTINY-CRC01. J Clin Oncol. 2020;38(suppl 15; abstr 4000). doi:10.1200/JCO.2020.38.15_suppl.4000