Impact of bevacizumab on the efficacy of antibody–drug conjugates as later-line treatment of basal-like immune-suppressed triple-negative breast cancer.

Abstract

1020 Background: Basal-like immune-suppressed (BLIS) triple-negative breast cancer (TNBC) is associated with a poor prognosis; however, prior analyses from the FUTURE and FUTURE-SUPER clinical trials indicated clinical responsiveness to anti-angiogenic therapy. We conducted this study to evaluate the safety and efficacy of combining bevacizumab with antibody–drug conjugates (ADCs) in patients with the BLIS subtype. Methods: The FUTURE 2.0 study (NCT05749588) is an ongoing, open-label, multi-arm phase II platform trial evaluating novel molecularly targeted agents in patients with histologically confirmed TNBC who progressed after ≥1 line of systemic therapy for recurrent or metastatic disease. This report presents results from the BLIS arms: arm C (HER2-low) and arm D (HER2-zero). In arm C, patients received either SHR-A1811 (anti-HER2 ADC, 4.8 mg/kg IV q3w) alone (C1) or with bevacizumab (15 mg/kg IV q3w) (C2). In arm D, patients received either SHR-A1921 (Trop2-targeted ADC, 3.0 mg/kg IV q3w) alone (D1) or with bevacizumab (7.5 mg/kg IV q3w) (D2). The primary endpoint was confirmed objective response rate (ORR). Safety was assessed in all treated patients with available safety data. Results: From April 2022 to October 2025, 100 women were enrolled: 60 assigned to bevacizumab-combination arms (C2 and D2) and 40 to ADC monotherapy arms (C1 and D1). All 100 patients completed at least one post-baseline assessment. Confirmed ORR was 40.0% (8/20; 95% CI: 21.9–61.3%) in C1, 86.7% (26/30; 95% CI: 70.3–94.7%) in C2, 40.0% (8/20; 95% CI: 21.9–61.3%) in D1, and 83.3% (25/30; 95% CI: 66.4–92.7%) in D2. All four arms met the protocol-specified ORR success criterion with high posterior probability. Median PFS was 9.2 months in the combination group versus 4.6 months in the monotherapy group (HR = 0.47; 95% CI: 0.30–0.74), indicating a clinically meaningful improvement. Grade ≥3 treatment-related adverse events occurred in 27.5% (11/40) of monotherapy patients and 33.3% (20/60) of combination patients. No treatment-related deaths occurred. Conclusions: This study provides preliminary evidence of synergy between bevacizumab and ADCs, supporting a promising new strategy—especially for basal-like, immune-suppressed TNBC. Phase III trials are ongoing to confirm the efficacy and safety of this combination. Clinical trial information: NCT05749588 . The efficacy table. ADC monotherapy ADC combined with bevacizumab A1811 N=20 A1921 N=20 Total N=40 A1811+ Bev N=30 A1921+ Bev N=30 Total N=60 ORR, n (%, 95% CI) 8 (40.0) 21.9 – 61.3 8 (40.0) 21.9 – 61.3 16 (40.0) 26.4 – 55.4 26 (86.7) 70.3 – 94.7 25 (83.3) 66.4 – 92.7 51 (85.0) 73.9 – 91.0 mPFS (mo, 95% CI) 4.9 4.1 – 5.7 4.4 3.7 – 5.1 4.6 3.9 – 5.3 9.1 7.2 – 11.1 9.3 8.2 – 10.5 9.2 7.3 – 11.0 HR in PFS, 95% CI 0.470.30 – 0.74 ( P =0.001)