Dato-DXd/Durvalumab Shows Promising Outcomes in Advanced TNBC

Results from arms 7 and 8 of the phase 1b/2 BEGONIA trial (NCT03742102) assessing datopotamab deruxtecan-dlnk (Dato-DXd; Datroway) plus durvalumab (Imfinzi) yielded anti-tumor activity for patients with advanced or metastatic triple-negative breast cancer, according to a poster presented at the 43rd Miami Breast Cancer Conference.

Arm 7 of the BEGONIA trial had a median duration of follow-up of 35.0 months and a confirmed objective response rate (ORR) of 79.0% (95% CI, 66.8%-88.3%), with a complete response (CR) rate of 12.9%, a partial response (PR) rate of 66.1%, stable disease rate of 12.9%, and progressive disease in 6.5% of patients. Of note, response rates were observed in patients with PD-L1–high and PD-L1–low tumors. The median duration of response (DOR) was 17.6 months (95% CI, 10.5-27.3), and the median progression-free survival (PFS) was 14.0 months (95% CI, 11.0-21.1). The median duration of treatment was 11.2 months for dato-DXd and 11.5 months for durvalumab.

In Arm 8, the median duration of follow-up was 10.7 months. The confirmed ORR was 81.8% (95% CI, 64.5%-93.0%), with a CR rate of 6.1%, PR rate of 75.8%, stable disease in 15.2%, and progressive disease in 3.0%. The median DOR and median PFS were too immature. The median duration of treatment for dato-DXd was 7.6 months and 8.3 months for durvalumab.

“The safety profile of dato-DXd [plus] durvalumab was manageable and consistent with the safety profiles of the 2 drugs when given separately. The percentage of patients who had a decrease in the size or number of tumors after treatment was 79% in arm 7 and 82% in arm 8,” Peter Schmid, FRCP, MD, PhD, clinical director of the Breast Cancer Centre and an honorary consultant medical oncologist at St. Bartholomew’s Hospital, and colleagues noted in the poster.

In Arm 7, 62 patients were enrolled with a median age of 53 years; 62.9% were White, followed by 24.2% who were Asian. Overall, 41.9% of patients did not receive prior treatment. Prior treatment modalities for early-stage disease included 53.2% having chemotherapy, 48.4% have radiotherapy, 46.8% having anthracyclines, and 41.9% having taxanes. Visceral metastases were noted in 64.5%, and central nervous system (CNS) metastases were reported in 3.2%.

In arm 8 (n = 33), the median age was 47 years, and 60.6% of patients were Asian followed by 33.3% who were White. Prior treatment did not occur in 39.4% of patients. Treatments for early-stage disease included 54.5% having chemotherapy, 48.5% each having anthracyclines and taxanes, and 21.2% having platinum compounds. Visceral metastases were noted in 63.6% of patients, and CNS metastases were seen in 9.1%.

In arm 7, patients with any PD-L1 expression were given dato-DXd at 6 mg/kg intravenously every 3 weeks plus durvalumab at 1120 mg intravenously every 3 weeks. In arm 8, patients with PD-L1–high tumors were given matched dosing.

Between both arms 7 and 8, 82.3% and 54.5% of patients discontinued dato-DXd, with 50.0% vs 48.5% due to disease progression, and 19.4% vs 6.1% due to adverse effects (AEs). Discontinuation of durvalumab was noted in 77.4% vs 54.5%, with 59.7% vs 48.5% due to disease progression, and 6.5% vs 6.1% due to AEs. In arm 7, 19.4% of patients remained on treatment at the time of the analysis compared with 45.5% in arm 8.

In part 1 of the study, the primary end point was safety and tolerability, with the secondary end points of ORR, PFS, DOR, and overall survival (OS). In part 2 of the study, the primary end point was ORR, and the secondary end points were PFS, DOR, PFS6, and OS.

Any treatment-emergent AE (TEAE) occurred in 100% of both arms 7 and 8. Any serious AEs were noted in 29.0% vs 15.2%. Any TEAE leading to death was noted in 1.6% vs 0%.

The most common TEAEs between arms 7 and 8 included stomatitis (69.4% vs 81.8%), nausea (67.7% vs 54.5%), alopecia (50.0% vs 39.4%), constipation (50.0% vs 30.3%), fatigue (48.4% vs 36.4%), and rash (33.9% vs 39.4%).

Reference

Schmid P, Wang HC, Lynce F, et al. Datopotamab deruxtecan (Dato-DXd) in combination with durvalumab as first-line treatment for unresectable locally advanced/metastatic triple-negative breast cancer: Results from arms 7 and 8 of the phase 1b/2 BEGONIA study. Presented at the 43rd Miami Breast Cancer Conference; Miami, FL; March 5-8, 2026.