Mecbotamab Vedotin Shows Positive OS Results in Soft Tissue Sarcoma

An improved overall survival (OS) was noted with mecbotamab vedotin (Mec-V) for patients with treatment-refractory leiomyosarcoma, liposarcoma, or undifferentiated pleomorphic sarcoma, according to results from a phase 2 trial (NCT03425279) presented at the Society for Immunotherapy of Cancer (SITC) 2025 Annual Meeting.¹

In the Mec-V monotherapy arm, the median OS was 18.4 months (95% CI, 7.2-not evaluable [NE]) vs 22.9 months (95% CI, 14.2-NE) in the Mec-V plus nivolumab (Opdivo) arm. The 12-month OS rate was 73% vs a historical rate of about 50% for approved agents in patients with recurrent soft tissue sarcoma.

The study also looked at the OS compared with approved agents, including trabectedin (Yondelis) with a median OS of 13.6 months (95% CI, 7.1-17.6), pazopanib (Votrient) of 12.5 months (95% CI, 10.6-12.8), and dacarbazine of 11.5 months (95% CI, 9.6-13.0).

For those with leiomyosarcoma, the median OS was 19.0 months (95% CI, 7.9-29.9); for liposarcoma, it was 21.7 months (95% CI, 3.7-NE); and for undifferentiated pleomorphic sarcoma, it was 21.5 months (95% CI, 5.0-NE).

The median progression-free survival was 2.5 months (95% CI, 1.4-5.8) in the monotherapy arm and 2.7 months (95% CI, 1.3-8.8) in the combination arm vs between 1.5 and 4.6 months for approved therapies.

Between the monotherapy and combination arms, the disease control rate (DCR) was 52% vs 55%, the partial response rate was 3% vs 9%, the stable disease rate was 49% vs 46%, the progressive disease rate was 46% vs 46%, and the overall response rate was 3% vs 9%.

"The data presented at SITC 2025 underscore the potential of Mec-V to meaningfully extend survival in patients with treatment-refractory soft tissue sarcomas—a population with few effective options,” Jay M. Short, PhD, chairman, chief executive officer, and co-founder of BioAtla, said in the press release.² “The prolonged OS observed suggests that early exposure to Mec-V may change the long-term clinical outcome among patients [with] these advanced sarcomas, potentially by helping to selectively eliminate AXL-expressing cancer cells that contribute to subsequent treatment resistance and poor outcomes."

The trial enrolled 79 patients, with 54 in the monotherapy arm and 25 in the combination arm. Patients were given Mec-V at 1.8 mg/kg every 2 weeks. Between both groups, the median age was 56 years, 56% of patients had an ECOG performance status of 1, 42% had 3 or more prior lines of therapy, and 44% had another sarcoma subtype aside from the ones previously listed.

The trial’s end points included DCR, the number of responders, the PFS rate at 12 weeks, OS, and treatment-emergent adverse effects (TEAEs). Patients 12 years and older with AXL-expressing locally advanced, unresectable, or metastatic sarcoma and measurable disease per RECIST v1.1 criteria were eligible for enrollment on the trial. Patients also needed to receive at least 1 anthracycline-based regimen and no more than 3 prior lines of approved systemic therapy for histologic subtypes that usually receive chemotherapy.

Any AE occurred in 95% of patients, 29% had grade 3 events, and 5% had grade 4 toxicities. Serious AEs occurred in 11% of patients, and 10% had treatment discontinuation because of AEs. No AEs led to death.

In the monotherapy arm, the most common AEs included fatigue (40%), nausea (37%), peripheral neuropathy (31%), abdominal pain (27%), and diarrhea (25%). In the combination arm, the most common AEs were decreased appetite (36%), fatigue (36%), anemia (32%), nausea (32%), and constipation (24%).

References

1. Druta M, Pollack SM, Conley AP, et al. 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. Presented at the Society for Immunotherapy of Cancer (SITC) 2025 Annual Meeting, National Harbor, MD; November 5-9, 2025.
2. BioAtla’s mecbotamab vedotin (Mec-V), an AXL-targeting ADC, demonstrates a median overall survival (OS) of 21.5 months in subtypes of refractory soft tissue sarcomas. News release. BioAtla. November 7, 2025. Accessed November 10, 2025. https://tinyurl.com/vaha6dc9