ENHERTU (fam-trastuzumab deruxtecan-nxki) gets US FDA nod for HER2-positive advanced gastric cancer

AstraZeneca and Daiichi Sankyo Company’s ENHERTU (fam-trastuzumab deruxtecan-nxki) has been approved in the US for the treatment of adult patients with locally advanced or metastatic HER2-positive gastric or gastroesophageal junction (GEJ) adenocarcinoma who have received a prior trastuzumab-based regimen.

The approval by the Food and Drug Administration (FDA) was based on the positive results from the randomised DESTINY-Gastric01 Phase II trial conducted in Japan and South Korea. In the trial, ENHERTU demonstrated a statistically significant and clinically meaningful improvement in overall survival (OS) and objective response rate (ORR) versus chemotherapy (irinotecan or paclitaxel) in patients with advanced gastric cancer or GEJ adenocarcinoma who had progressed on at least two or more prior regimens including trastuzumab plus a fluoropyrimidine- and a platinum-containing chemotherapy combination.

Dave Fredrickson, Executive VP, Oncology Business Unit, said, “Today’s approval of ENHERTU represents the first HER2-directed medicine in a decade for patients with HER2-positive metastatic gastric cancer. The results from the DESTINY-Gastric01 trial highlight the potential to change clinical practice, showing a 41 percent improvement in survival and a response rate more than three times higher with ENHERTU compared to chemotherapy. We are thrilled to bring this important medicine to more patients and physicians in the US.”

Antoine Yver, Executive VP and Global Head, Oncology Research and Development, Daiichi Sankyo, said, “ENHERTU is the first antibody drug conjugate to receive approval in the US for the treatment of patients with metastatic gastric cancer, and represents a major advance in managing this difficult-to-treat disease. This second indication in the US represents an important step forward in our ambitious plan to accelerate the development of ENHERTU across a broad range of HER2-targetable cancers.”

In a pre-specified interim analysis from the DESTINY-Gastric01 trial, patients treated with ENHERTU had a 41 per cent reduction in the risk of death versus patients treated with chemotherapy (based on a hazard ratio [HR] of 0.59; 95 per cent confidence interval [CI] 0.39-0.88; p=0.0097) with a median OS of 12.5 months versus 8.4 months.

Confirmed ORR, assessed by independent central review was a major efficacy outcome. Results showed a confirmed ORR of 40.5 per cent in patients treated with ENHERTU (n=126) compared to 11.3 per cent in patients treated with chemotherapy (n=62). Patients treated with ENHERTU had a 7.9 per cent complete response rate and a 32.5 per cent partial response rate compared to a complete response rate of 0 per cent and a partial response rate of 11.3 per cent for patients treated with chemotherapy.

ENHERTU demonstrated a median progression-free survival (PFS) of 5.6 months compared to 3.5 months with chemotherapy (HR=0.47; 95 per cent CI 0.31-0.71). Additionally, ENHERTU showed a median duration of response (DoR) of 11.3 months versus 3.9 months with chemotherapy.

Results from the DESTINY-Gastric01 trial were published in The New England Journal of Medicine in June 2020.

ENHERTU is approved with Boxed WARNINGS for interstitial lung disease (ILD) or pneumonitis and embryo-fetal toxicity. This is the second indication approved for ENHERTU in the US following the accelerated approval for adult patients with unresectable or metastatic HER2-positive breast cancer who have received two or more prior anti-HER2-based regimens in the metastatic setting based on the DESTINY-Breast01 trial.

ENHERTU was previously granted Priority Review, Breakthrough Therapy Designation (BTD) in HER2-positive metastatic gastric cancer and Orphan Drug Designation (ODD) for gastric cancer by the FDA. Two additional Phase II trials, DESTINY-Gastric02 and DESTINY-Gastric03, are underway, further evaluating treatment with ENHERTU in patients with HER2-positive metastatic gastric cancer.