FDA Grants Priority Review to Trastuzumab in HER2+ Solid Tumors


If approved, trastuzumab deruxtecan would be the first HER2-directed antibody-drug conjugate for a tumor-agnostic indication.

Tumor cell: © nevio - stock.adobe.com

Tumor cell: © nevio - stock.adobe.com

  • The FDA has granted priority review to the supplemental biologics license application (sBLA) of trastuzumab deruxtecan (T-Dxd; Enhertu) for unresectable or metastatic HER2-positive (+) solid tumors.
  • The priority review follows the breakthrough drug designation trastuzumab deruxtecan received in August 2023.
  • The application is based on findings from the DESTINY-PanTumor02 study (NCT04482309).

T-Dxd has been granted priority review by the FDA for the treatment of patients with unresectable or metastatic HER2+ tumors who have received prior treatment or who have no suitable treatment options available.1

If approved, this would be the first tumor-agnostic HER2-directed therapy and antibody-drug conjugate.

Priority review is given to applications for treatments that, if approved, would deliver significant improvements in efficacy or safety over other available options. The Prescription Drug User Fee Act target action date is in the second quarter of 2024.

“With meaningful clinical activity, this could represent a new treatment option. If it becomes available, this is something that I think our oncologists will be able to pursue as a true testing option,” Funda Meric-Bernstam, MD, chair of the Department of Investigational Cancer Therapeutics at MD Anderson Cancer Center and one of the investigators of DESTINY-PanTumor02, told Targeted OncologyTM, in an interview.

The application is based on findings from the phase 2 DESTINY-PanTumor02 study. Primary results were published in the Journal of Clinical Oncology and presented at the 2023 European Society for Medical Oncology Congress.1 Across 267 patients with endometrial, cervical, ovarian, bladder, biliary tract, pancreatic, and other tumors, the overall response rate was 37.1% (n = 99; 95% CI, 31.3%-43.2%) at a median follow-up of 12.75 months.2 Responses were observed across all tumor cohorts. The median duration of response was 11.3 months (95% CI, 9.6-17.8).

Regarding survival, the median progression-free survival was 6.9 months (95% CI, 5.6-8.0), and the median overall survival was 13.4 months (95% CI, 11.9-15.5).

For safety, grade 3 or greater treatment-related adverse events were observed in 40.8% of patients. Adjudicated treatment-related interstitial lung disease was reported in 10.5% of patients with 3 deaths.

“Today’s priority review for the first tumor-agnostic submission for [T-Dxd] reflects the potential of this medicine to redefine the treatment of HER2-expressing cancers. Biomarkers for HER2 expression are already established in breast and gastric cancers, but we must now define them across tumor types. We will continue working closely with the FDA to bring this potential first tumor-agnostic HER2-targeted medicine and biomarker to patients as quickly as possible,” said Susan Galbraith, executive vice president of oncology research and development at AstraZeneca, in a press release.1

1. Enhertu granted priority review in the US for patients with metastic HER2-positive solid tumors. News release. AstraZeneca. January 29, 2024. Accessed January 29, 2024. http://tinyurl.com/mty53a77
2. Meric-Bernstam F, Makker V, Oaknin A, et al. Efficacy and safety of trastuzumab deruxtecan (T-DXd) in patients (pts) with HER2-expressing solid tumors: DESTINY-PanTumor02 (DP-02) interim results. J Clin Oncol. 2023;41(suppl 17):LBA3000.
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