Trastuzumab Deruxtecan Gets Priority Review for Metastatic HER2+ Solid Tumors

The Food and Drug Administration has accepted for Priority Review the supplemental Biologics License Application (sBLA) for trastuzumab deruxtecan for the treatment of adults with unresectable or metastatic human epidermal growth factor receptor 2 (HER2)-positive (immunohistochemistry [IHC] 3+) solid tumors who have received prior treatment or who have no satisfactory alternative treatment options.

Trastuzumab deruxtecan is a HER2-directed antibody and topoisomerase inhibitor conjugate currently marketed under the brand name Enhertu (fam-trastuzumab deruxtecan-nxki) for treatment of breast cancer, non-small cell lung cancer, and gastric or gastroesophageal junction adenocarcinoma.

The sBLA submission was supported by data from the ongoing, open-label, multicenter, multi-cohort, phase 2 DESTINY-PanTumor02 trial (ClinicalTrials.gov Identifier: NCT04482309), which assessed the efficacy and safety of trastuzumab deruxtecan for the treatment of selected HER2-expressing tumors. The trial included 7 cohorts: urothelial bladder cancer, biliary tract cancer, cervical cancer, endometrial cancer, ovarian cancer, pancreatic cancer, and rare tumors. The primary endpoint was confirmed objective response rate (ORR).

At a median follow-up of 12.75 months, results showed a confirmed ORR of 37.1% (n=99 [95% CI, 31.3–43.2]) in all patients. Median duration of response (DOR) was 11.3 months (95% CI, 9.6–17.8). Median progression free survival (PFS) was 6.9 months (95% CI, 5.6–8.0) and median overall survival was 13.4 months (95% CI, 11.9–15.5). 

Among patients with central HER2 IHC3+ expression (n=75), trastuzumab deruxtecan demonstrated a confirmed ORR of 61.3% (95% CI, 49.4–72.4). Median DOR was 22.1 months (95% CI, 9.6, not reached), median PFS was 11.9 months (95% CI, 8.2–13.0), and median OS was 21.1 months (95% CI, 15.3–29.6). 

“The clinical benefit seen across HER2-expressing metastatic solid tumors in the DESTINY-PanTumor02 trial and ongoing data from the Enhertu clinical development program continues to demonstrate the potential of this medicine beyond its approved indications,” said Ken Takeshita, MD, Global Head, R&D, Daiichi Sankyo. “If approved, Enhertu could become the first HER2-directed therapy and antibody drug conjugate with a tumor-agnostic indication, providing patients with a potential new treatment option.”

A Prescription Drug User Fee Act target date has been set for the second quarter of 2024.

This article originally appeared on MPR