T-Bren (BL-M07D1) in patients with recurrent or metastatic (R/M) ovarian cancer: Results from two phase II studies.

3003 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 studies, T-Bren demonstrated encouraging anti-tumor activity with a manageable safety profile in patients (pts) with solid tumors. Results of safety/efficacy from two phase II studies in pts with R/M ovarian cancer (OC) are presented. Methods: Two studies evaluated T-Bren as monotherapy in pts with R/M platinum-resistant (disease progression within 6 months of the last dose of platinum-based chemotherapy) and platinum-sensitive OC. Pts with R/M OC were treated at 3.8mg/kg or 4.4mg/kg D1 Q3W. Primary endpoints include ORR and RP2D. Pts were selected for HER2 expression (ultra-low/1+/2+/3+). Results: As of Nov 30, 2025, a total of 65 pts were enrolled at 3.8 (N = 51), or 4.4mg/kg (N = 14) D1Q3W. Of all pts, 28 (43.1%) pts previously received ≥3 lines of therapy. The most common grade 3 and above hematologic TRAEs were thrombocytopenia (41.5%), leukopenia (35.4%), neutropenia (35.4%), and anemia (29.2%); the most common grade 3 and above non-hematologic TRAEs were asthenia (6.2%), lymphocyte count decrease (6.2%). Grade 3 and above TRAEs, which were predominantly hematologic in nature, were able to be effectively managed with standard supportive measure including dose reductions, as demonstrated by the TRAE leading to discontinuation rate of 3.1%. No ILD was observed. No new safety signals were identified. Median follow-up was 7.8 mo. Among pts at 3.8mg/kg D1 Q3W, confirmed ORR (cORR) was 88.9% in platinum-sensitive OC and 47.5% in platinum-resistant OC. mPFS had not reached and 9-mo PFS rate was 85.7% in platinum-sensitive OC and 61.2% in platinum-resistant OC. Efficacy results are summarized in the table below. Conclusions: T-Bren has demonstrated promising anti-tumor activity with a manageable safety profile in heavily pre-treated pts with R/M OC. Dose 3.8mg/kg D1 Q3W was chosen as the RP3D. Phase III study of platinum-resistant OC is in preparation. Clinical trial information: NCT06031584; NCT06131450 . Total (N=63) 3.8mg/kgTotal (N=49) 3.8mg/kgPlatinum-sensitive (N=9) 3.8mg/kgPlatinum-resistant(N = 40) Median prior LoT (range) 2 (1-8) 2 (1-6) 2 (1-4) 2 (1-6) ORR, % (95% CI) 57.1 (44.0, 69.5) 59.2 (44.2, 73.0) 88.9 (51.8, 99.7) 52.5 (36.1, 68.5) cORR, % (95% CI) 49.2 (36.4, 62.1) 55.1 (40.2, 69.3) 88.9 (51.8, 99.7) 47.5 (31.5, 63.9) DCR, % (95% CI) 88.9 (78.4, 95.4) 89.8 (77.8, 96.6) 100 (66.4, 100) 87.5 (73.2, 95.8) mPFS (mo) (95% CI) 9.3 (7.0, NR) NR (7.0, NR) NR (5.6, NR) NR (7.0, NR) 9-mo PFS rate, % (95% CI) 50.1 (24.0, 71.6) 67.5 (46.0, 81.9) 85.7 (33.4, 97.9) 61.2 (34.5, 79.7) *All pts who received at least one dose of T-Bren, excluding those still ongoing with insufficient follow up were used for efficacy analysis.