Phase II study of T-Bren (BL-M07D1) monotherapy or in combination with pertuzumab in patients with treatment-naïve HER2-positive unresectable locally advanced or metastatic (LA/M) breast cancer.

1049 Background: T-Bren is a HER2-directed antibody-drug conjugate (ADC) consisting of an anti-HER2 monoclonal antibody linked to a potent topoisomerase I inhibitor (Ed-04). In phase I study, T-Bren demonstrated encouraging antitumor activity with a manageable safety profile in patients (pts) with HER2-positive unresectable LA/M breast cancer (BC) who had failed standard treatments. Results of safety and efficacy from a phase II study assessing T-Bren monotherapy or in combination with pertuzumab in treatment-naïve HER2-positive unresectable LA/M BC are presented. Methods: Treatment-naïve pts with HER2-positive (IHC3+, or IHC2+/ISH+) unresectable LA/M BC were treated with T-Bren monotherapy at 4.4mg/kg Q3W (cohort A) or T-Bren 4.4mg/kg Q3W in combination with pertuzumab (cohort B). Primary endpoints were ORR and RP2D for combination treatment. Results: As of Nov 30, 2025, a total of 83 pts were enrolled and treated in cohort A (n = 43) and cohort B (n = 40). All pts were included in the analysis (see table below). The median follow-up was 10.6 months. In cohort A, ORR was 93.0%, confirmed ORR (cORR) was 86.0%. In cohort B, ORR and cORR were 87.5%. Median PFS have not reached in either cohort. The landmark PFS rate at 12-months was 79.1% in cohort A and 90.8% in cohort B. The most common grade 3 and above hematologic TRAEs in both cohorts were neutropenia (51.8%), anemia (37.3%), leukopenia (36.1%), and thrombocytopenia (26.5%); the most frequent grade 3 and above non-hematologic TRAEs were weight decreased (7.2%), hypokalemia (6.0%), and nausea (6.0%). Grade 3 and above TRAEs were able to be effectively managed with standard supportive measure including dose reductions, as demonstrated by the TRAE leading to discontinuation rate of 4.8%. No treatment related death or ILD was reported. Conclusions: T-Bren as monotherapy or in combination with pertuzumab has demonstrated a promising antitumor activity and a manageable safety profile in pts with treatment-naïve HER2-positive unresectable LA/M BC. Phase III study assessing T-Bren in treatment-naïve HER2-positive unresectable LA/M BC is in preparation. Clinical trial information: NCT06445400 . Cohort A: T-Bren 4.4 mg/kg D1Q3W (N=43) Cohort B: T-Bren 4.4 mg/kg D1Q3W+ pertuzumab D1Q3W (N=40) Total (N=83) ORR, % (95% CI) 93.0 (80.9, 98.5) 87.5 (73.2, 95.8) 90.4 (81.9, 95.7) cORR, % (95% CI) 86.0 (72.1, 94.7) 87.5 (73.2, 95.8) 86.7 (77.5, 93.2) DCR, % (95% CI) 100 (91.8, 100) 97.5 (86.8, 99.9) 98.8 (93.5, 100) 12-mo PFS rate, % (95% CI) 79.1 (32.9, 95.2) 90.8 (74.1, 97.0) 89.9 (77.8, 95.6) 12-mo OS rate, % (95% CI) 100 (100, 100) 95.0 (81.5, 98.7) 97.4 (89.9, 99.3)