T-DXd Receives FDA Priority Review in Metastatic HER2+ Solid Tumors

The FDA has set a Prescription Drug User Fee Action date within the second quarter of 2024 for their decision on approving T-DXd.

The FDA has granted priority review to a supplemental biologics license application (sBLA) for trastuzumab deruxtecan (T-DXd; Enhertu) in the management of metastatic or unresectable HER2-positive solid tumors that progressed on prior treatment, according to a news release from AstraZeneca.¹

The regulatory agency has set a Prescription Drug User Fee Action date within the second quarter of 2024 for their decision on approving T-DXd in the aforementioned population. Patients with solid tumors must have an immunohistochemistry score of 3+, received prior treatment, or have no alternative to be eligible for treatment.

“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,” Susan Galbraith, executive vice president of Oncology Research and Development at AstraZeneca, said in the news release. “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.”

Supporting data for the sBLA in this indication came from the phase 2 DESTINY-PanTumor02 trial (NCT04482309) assessing the safety and efficacy of T-DXd in those with previously treated HER2-positive solid tumors. According to data published in the Journal of Clinical Oncology, the agent elicited an investigator-assessed median progression-free survival (PFS) of 6.9 months (95% CI, 5.6-8.0) and a median overall survival (OS) of 13.4 months (95% CI, 11.9-15.5) across all cohorts.² Additionally, the confirmed objective response rate (ORR) was 37.1% (95% CI, 31.3%-43.2%), and the median duration of response (DOR) was 11.3 months (95% CI, 9.6-17.8).

The most common grade 3 or higher treatment-related adverse effects (TRAEs) included neutropenia (10.9%) and anemia (10.9%). Additionally, 8.6% of patients discontinued treatment, and 20.2% required dose reductions due to TRAEs. Overall, investigators reported that the safety profile of T-DXd in the DESTINY-PanTumor02 trial was comparable with prior reports.

“These primary analysis results confirm the efficacy shown at an interim analysis of the DESTINY-PanTumor02 trial, with responses leading to clinically meaningful survival outcomes across a broad range of HER2-expressing solid tumors,” lead study author Funda Meric-Bernstam, MD, chair of Investigational Cancer Therapeutics at The University of Texas, MD Anderson Cancer Center, said in a news release on these data.³ “Based on these results, [T-DXd] has the potential to change the course of disease for certain patients with HER2-expressing advanced cancers who have limited treatment options and currently no approved HER2-directed therapies.”

In the international, multi-cohort, open-label DESTINY-PanTumor02 trial, investigators administered T-DXd at 6.4 mg/kg to patients with previously treated HER2-expressing solid tumors, which included those with biliary tract cancer, bladder cancer, cervical cancer, endometrial cancer, ovarian cancer, pancreatic cancer, and other disease types.

The trial’s primary end point was ORR based on investigator assessment. Secondary end points included DOR, PFS, disease control rate, OS, safety, and pharmacokinetics.

Patients 18 years and older with locally advanced, unresectable, or metastatic disease and progression after prior therapy were able to enroll on the trial. Other eligibility criteria included having measurable disease based on RECIST v1.1 criteria and adequate cardiac, renal, and hepatic function.

References

1. Enhertu granted priority review in the US for patients with metastatic HER2-positive solid tumours. News release. AstraZeneca. January 29, 2024. Accessed January 29, 2024. http://tinyurl.com/yc8ak68t
2. Meric-Bernstam F, Makker F, Oaknin A, et al. Efficacy and safety of trastuzumab deruxtecan in patients With HER2-expressing solid tumors: primary results from the DESTINY-PanTumor02 phase II trial. J Clin Oncol. 2023;42(1):47-58. doi:10.1200/JCO.23.02005
3. Enhertu demonstrated clinically meaningful survival across multiple HER2-expressing advanced solid tumours in DESTINY-PanTumor02 phase II trial. News release. AstraZeneca. October 23, 2023. Accessed January 29, 2024. http://tinyurl.com/5fxxedhw