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

• The FDA has accepted the biologics license application (BLA) for datopotamab deruxtecan (Dato-DXd) for the treatment of patients with unresectable or metastatic hormone receptor-positive (HR+), HER2-negative (HER2–) breast cancer who have received prior systemic therapy.
• A Prescription Drug User Fee Act target action date has been set for Q1 2025.
• The FDA is also reviewing a BLA for Dato-DXd in non-small cell lung cancer (NSCLC).

The FDA accepted the BLA of Dato-DXd, a TROP2-directed antibody-drug conjugate, in patients with HR+, HER2– breast cancer that has been previously treated with systemic therapy. A PDUFA target action date has been set for the first quarter of 2025.¹

The BLA is supported by findings from the phase 3 TROPION-Breast01 trial (NCT05104866). According to data presented at the 2023 European Society of Medical Oncology Annual Congress, Dato-DXd reduced the risk of disease progression or death by 37% compared with investigator’s choice of chemotherapy (HR, 0.63; 95% CI, 0.52-0.76; P <.001) as assessed by blinded independent central review. The confirmed objective response rates (ORR) were 36.4% and 22.9% for Dato-DXd and chemotherapy, respectively.²

Progression-free survival (PFS) findings were presented at the 2023 San Antonio Breast Cancer Symposium. A median PFS of 6.9 months was observed in patients treated with Dato-DXd (n = 365) vs 4.9 months in patients who received chemotherapy (n = 367; HR, 0.63; 95% CI, 0.52-0.76; P <.0001).³

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

In February 2024, the FDA accepted a BLA for Dato-DXd for the treatment of nonsquamous NSCLC, and a PDUFA target action date is anticipated in the fourth quarter of 2024.⁴

About TROPION-Breast01

TROPION-Breast01 is a phase 3, open-label, randomized study of Dato-DXd vs investigator’s choice of chemotherapy in patients with inoperable or metastatic HR+, HER2– breast cancer who have received 1 or 2 prior lines of systemic therapy. The study has an enrollment of 732 patients across sites in 10 states in the US and 19 additional countries.⁵

The study’s primary end points are PFS and overall survival, and secondary end points include ORR, duration of response, PFS by investigator assessment, disease control rate, time to first subsequent therapy, and time to second subsequent therapy.

The study is active but not recruiting and has an estimated completion date of August 15, 2025.

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. April 2, 2024. Accessed April 2, 2024. https://tinyurl.com/mr4dj53s

2. Datopotamab deruxtecan significantly extended progression-free survival vs. chemotherapy in patients with HR-positive, HER2-low or negative breast cancer in TROPION-Breast01 phase III trial. News release. AstraZeneca. October 23, 2023. Accessed April 2, 2024. https://tinyurl.com/yc2m973a

3. 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

4. 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/w595xw6u

5. A phase-3, open-label, randomized study of Dato-DXd versus investigator's choice of chemotherapy (ICC) in participants with inoperable or metastatic HR-positive, HER2-negative breast cancer who have been treated with one or two prior lines of systemic chemotherapy (TROPION-Breast01). ClinicalTrials.gov. Updated January 25, 2024. Accessed April 2, 2024. https://clinicaltrials.gov/study/NCT05104866