523 Median OS of 21.5 months among 44 patients with treatment-refractory leiomyosarcoma, liposarcoma, and undifferentiated pleomorphic sarcoma treated with mecbotamab vedotin, an AXL-targeting ADC

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Background Despite advances in therapy, sarcomas remain a significant unmet need. 1 2 Median OS among patients with treatment-refractory soft tissue sarcomas (STS) treated with either trabectedin, pazopanib, or eribulin has been reported to range from 12.5 to 13.6 months.3 4 AXL, a cell-surface receptor tyrosine kinase, is highly expressed in several STS subtypes and has been shown to drive increased metastasis, resistance to chemotherapy, and poor outcomes.5 Mecbotamab vedotin (Mec-V, BA3011, Conditionally Active Biologic CAB-AXL-ADC) is designed to reduce off-tumor toxicity and improve pharmacokinetics by conditionally binding to AXL under low-pH conditions (pH<6.7) of the tumor microenvironment.6 7 Methods A phase 2 open-label study evaluated Mec-V among adult and adolescent patients with AXL-expressing locally advanced, unresectable, or metastatic STS with measurable disease by RECIST v1.1. Patients received either Mec-V monotherapy 1.8 mg/kg every 2 weeks (Q2W) or Mec-V + nivo combination therapy.Results Phase 1 and 2 included 44 patients with STS, of whom 33 received Q2W and 11 received Q2W Mec-V + nivo. This report focuses upon the long term follow up among patients with leiomyosarcoma (LMS, n=27), liposarcoma (LPS, n=9), or undifferentiated pleomorphic sarcoma (UPS, n=8). Patients had a median of 2 prior lines of treatment. Most TEAEs were low grade and reversible; related grade 3/4 TEAE of special interest were neutropenia (21%), hepatic transaminase elevations (16%), and hyperglycemia (3%). No grade 5 TEAE were observed and 9% of related TEAE led to treatment discontinuation. 5% and 52% experienced partial response or disease control respectively. As of March 24, 2025, the OS with Mec-V in LMS, LPS, and UPS was 21.5 months ( table 1). Landmark OS at 1 year was 73%. Median OS in Mec-V monotherapy vs. Mec-V + nivo combination therapy was 18.4 vs 22.9 months, respectively (table 1), across STS subtypes with 45% of events recorded.Conclusions Patients with heavily pretreated leiomyosarcoma, liposarcoma, and undifferentiated mean pleomorphic sarcoma had a median OS of 21.5 months after treatment with Mec-V, a conditionally binding, AXL-targeting ADC. The manageable safety profile remained consistent with previous reports. Further evaluation of Mec-V, potentially in novel combinations, is justified.Trial Registration NCT03425279References Zhang G, Liu Z, Xu H, Yang Q, et al. miR-124-3p inhibits cell growth and enhances chemosensitivity of osteosarcoma cells by targeting STAT3. Oncol Lett. 2018;15:2726–2734.Howlader N, Noone AM, Krapcho M, et al. SEER Cancer Statistics Review, 1975–2017. National Cancer Institute. Bethesda, MD. https://seer.cancer.gov/csr/1975_2017/. Based on November 2019 SEER data submission, posted April 2020.Italiano A, Delva F, Mathoulin-Pélissier S, et al. Frequency, characteristics, and management of gastrointestinal stromal tumors in daily practice. Cancer. 2011;117:1049-1054.Isakoff MS, Bielack SS, Meltzer P, Gorlick R, et al. Osteosarcoma: current treatment and a collaborative pathway to success. J Clin Oncol. 2015;33:3029-3035.Gay CM, Balaji AK, Byers LA, et al. Giving AXL the axe: targeting AXL in human malignancy. Br J Cancer. 2017;116:415-423.Chang HW, et al. Proc Natl Acad Sci USA. 2021;118(9):e2020606118.Dy GK, Yau E, Rotow J, et al. Exploratory analysis of overall survival among non-small cell lung cancer (NSCLC) patients with mutated KRAS in a phase 2 trial of mecbotamab vedotin (CAB-AXL-ADC). Presented at: European Lung Cancer Congress; 2025 Mar 26–29; Paris, France. Poster 98P.Ethics Approval The study was performed in accordance with ethical principles that have their origin in the Declaration of Helsinki and are consistent with ICH/GCP.Abstract 523 Table 1Best overall response

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