FDA Accepts BLA for Dato-DXd in Metastatic HR+/HER2– Breast Cancer

The European Medicines Agency (EMA) previously validated a marketing authorization application for dato-DXd as a treatment for those with previously treated HR-positive, HER2-negative breast cancer based on data from the TROPION-Breast01 trial in March 2024.

The FDA has accepted a biologics license application (BLA) for datopotamab deruxtecan (dato-DXd) as a treatment for adult patients with previously treated unresectable or metastatic hormone receptor (HR)–positive, HER2-negative breast cancer, according to a press release from developers AstraZeneca and Daiichi Sankyo.¹

The regulatory agency has set a Prescription Drug User Fee Action date within the first quarter of 2025 for its decision on approving dato-DXd in this indication.

Supporting data for the BLA came from the phase 3 TROPION-Breast01 trial (NCT05104866). Investigators presented updated findings from the trial at the 2023 San Antonio Breast Cancer Symposium (SABCS).

Per blinded independent central review (BICR), the median progression-free survival (PFS) was 6.9 months with dato-DXd vs 4.9 months with chemotherapy (HR, 0.63; 95% CI, 0.52-0.76; P <.0001).² The median PFS in each respective arm based on investigator assessment was 6.9 months (95% CI, 5.9-7.1) and 4.5 months (95% CI, 4.2-5.5; HR, 0.64; 95% CI, 0.53-0.76). In each respective arm, the PFS rate per investigator assessment was 55.2% vs 36.9% at 6 months, 34.7% vs 20.9% at 9 months, and 21.7% vs 9.9% at 12 months.

Any-grade treatment-related adverse effects (TRAEs) affected 94% and 86% of patients in the dato-DXd and chemotherapy arms, respectively. Common any-grade treatment-related toxicities in each arm included neutropenia (11% vs 42%) and stomatitis (50% vs 13%).

“TROPION-Breast01 met its primary end point by demonstrating a statistically significant and clinically meaningful improvement in PFS by both BICR as well as investigator-assessed PFS. The results support dato-DXd as a potential new therapeutic option for patients with endocrine-resistant, metastatic HR-positive breast cancer,” Aditya Bardia, MD, MPH, a medical oncologist at Massachusetts General Hospital and an associate professor of medicine at Harvard Medical School in Boston, said in a presentation of these findings.²

Patients in the TROPION-Breast01 trial were assigned 1:1 to receive dato-DXd at 6 mg/kg intravenously on day 1 every 3 weeks (n = 365) or investigator’s choice of chemotherapy (n = 367). Options for chemotherapy included eribulin mesylate (Halaven), vinorelbine, or gemcitabine on days 1 and 8 every 3 weeks plus capecitabine on days 1 to 14 every 3 weeks.

The trial’s coprimary end points were PFS per RECIST v1.1 criteria and overall survival. Secondary end points included overall response rate, safety, patient-reported outcomes, and time to first subsequent therapy.

Patients with HR-positive, HER2-negative breast cancer previously treated with 1 or 2 prior lines of chemotherapy in the inoperable or metastatic setting were eligible for enrollment on the trial. Other eligibility criteria included having an ECOG performance status of 0 or 1.

“Despite marked progress in the treatment of HR-positive, HER2-negative breast cancer, most patients with advanced disease develop endocrine resistance and [have] the prospect of 1 or several lines of chemotherapy,” Susan Galbraith, executive vice president of Oncology Research & Development at AstraZeneca, said in the press release.¹ “If approved, datopotamab deruxtecan has the potential to provide these patients an efficacious and better tolerated alternative to conventional chemotherapy.”

The FDA previously accepted a BLA for dato-DXd for adult patients with nonsquamous advanced non–small cell lung cancer (NSCLC) in February 2024.3 Supporting data for this application came from the phase 3 TROPION-Lung01 trial (NCT04656652).

The European Medicines Agency (EMA) previously validated a marketing authorization application for dato-DXd as a treatment for those with previously treated HR-positive, HER2-negative breast cancer based on data from the TROPION-Breast01 trial in March 2024.4 The agency also validated a marketing application for dato-DXd as a treatment for those with nonsquamous NSCLC based on findings from the TROPION-Lung01 trial.

References

1. Datopotamab deruxtecan biologics license application accepted in the US for patients with previously treated metastatic HR-positive, HER2-negative breast cancer. News release. AstraZeneca and Daiichi Sankyo. April 2, 2024. Accessed April 2, 2024. https://tinyurl.com/mv3f3wa5
2. Bardia A, Jhaveri K, Im SA, et al. Randomized phase 3 study of datopotamab deruxtecan vs chemotherapy for patients with previously-treated inoperable or metastatic hormone receptor-positive, HER2-negative breast cancer: results from TROPION-Breast01. Presented at: 2023 San Antonio Breast Cancer Symposium; December 5-9, 2023; San Antonio, TX. Abstract GS02-01
3. Datopotamab deruxtecan biologics license application accepted in the US for patients with previously treated advanced nonsquamous non-small cell lung cancer. News release. AstraZeneca. February 19, 2024. Accessed April 2, 2024. http://tinyurl.com/2v5k3yhc
4. Two datopotamab deruxtecan applications validated in the EU for patients with advanced nonsquamous non-small cell lung cancer or HR-positive, HER2-negative breast cancer. News release. AstraZeneca. March 4, 2024. Accessed April 2, 2024. https://tinyurl.com/3va3hp8n