Mecbotamab Vedotin Shows Potential to Extend Survival in Treatment-Refractory Soft Tissue Sarcomas

Treatment with the AXL-targeting antibody-drug conjugate mecbotamab vedotin (Mec-V) led to a median overall survival (OS) of 21.5 months (95% CI, 14.2-29.9) in patients with treatment-refractory leiomyosarcoma (LMS), liposarcoma, and undifferentiated pleomorphic sarcoma (UPS; n = 44), according to data from part 1 of a phase 2 trial (NCT03425279).1

The findings, which were shared during the 2025 SITC Annual Meeting, showed that Mec-V led to meaningful longer median OS compared with approved agents. When administered as a monotherapy at a dose of 1.8 mg/kg every 2 weeks (Q2W; n = 33), the median OS was 18.4 months (95% CI, 7.2-not evaluable [NE]). When given at the same dose in combination with nivolumab (Opdivo; n = 11), the median OS was 22.9 months (95% CI, 14.2-NE). In comparison, the median OS observed with other approved agents like eribulin (Halaven), pazopanib (Votrient), and dacarbazine was 13.5 months (95% CI, 10.9-15.6), 12.5 months (95% CI, 10.6-12.8), and 11.5 months (95% CI, 9.6-13.0), respectively.

Moreover, in those with LMS, liposarcoma, and UPS, the median OS with the ADC was 19.0 months (95% CI, 7.9-29.9), 21.7 months (95% CI, 3.7-NE), and 21.5 months (95% CI, 5.0-NE), respectively. The 12-month OS rate was 73%, which compares favorably with a historic 12-month OS rate of approximately 50% that has been reported for approved agents in recurrent soft tissue sarcoma.

Mec-V monotherapy led to a disease control rate (DCR) of 52%. Moreover, the objective response rate (ORR) was 3%, which included a partial response (PR); 49% of patients had stable disease (SD) and 46% experienced disease progression. The DCR achieved with Mec-V plus nivolumab was slightly higher, at 55%. The combination induced an ORR of 9%, which included a PR; 46% of patients had SD and 46% experienced PD. The median progression-free survival (PFS) with the monotherapy and the combination were 2.5 months (95% CI, 1.4-5.8) and 2.7 months (95% CI, 1.3-8.8), respectively, which was noted to be generally consistent with current approved drugs, which have median PFS ranging from 1.5 months to 4.6 months.

“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, stated in a news release.2 “The prolonged OS observed suggests that early exposure to Mec-V may change the long-term clinical outcome among patients suffering from these advanced sarcomas, potentially by helping to selectively eliminate AXL-expressing cancer cells that contribute to subsequent treatment resistance and poor outcomes.”

What is the study design for part 1 of the phase 2 trial examining Mec-V?

The open-label study included patients who were at least 18 years of age and who had AXL-expressing, locally advanced, unresectable, or metastatic sarcoma and measurable disease by RECIST v1.1 criteria.1 Patients were required to have previously received at least 1 anthracycline-containing regimen and no more than 3 prior lines of approved systemic treatment if they had a histologic subtype that is generally treated with chemotherapy.

After undergoing a screening period, patients received the ADC at 1.8 mg/kg Q2W or the ADC at 1.8 mg/kg plus nivolumab Q2W. Patients received at least 3 cycles of treatment, which were comprised of 15 days each. Tumor assessments were done during the screening period, on day 15 of cycle 2, and on day 1 of cycle 3+. The key end points of the study were DCR, number of responders, PFS rate at week 12, OS, and treatment-emergent adverse effects (TEAEs).

The data cutoff date for the findings shared at SITC 2025 was March 25, 2025. In the total population (n = 79), the mean age was 56 years (range, 23-80). More than half of patients had an ECOG performance status of 1 (56%). Sarcoma subtypes included LMS (34%), UPS (10%), liposarcoma (11%), or other soft tissue sarcoma (44%). Moreover, 20% of patients had received 1 prior systemic therapy, 37% received 2 prior lines, and 42% had received 3+ prior lines; this information was not available for 1 patient. Patients had received a mean of 15 weeks of the ADC (range, 2-63). The efficacy analysis set was comprised of those with LMS, liposarcoma, and UPS (n = 44).

What was learned about the safety profile of Mec-V?

The ADC was reported to be generally well tolerated. Ninety-five percent of all patients (n = 79) experienced any adverse effects (AEs); these effects were related to treatment for 81% of patients. Among those who experienced treatment-related AEs, 29% experienced a grade 3 AE and 5% experienced a grade 4 AE. Any related serious AEs were observed in 11% of patients.

AEs were reported to be generally low grade, transient, and manageable. The most common TEAEs reported in those who received Mec-V monotherapy (n = 54) were fatigue, nausea, peripheral neuropathy, abdominal pain, diarrhea, headache, anemia, decreased appetite, neutropenia, vomiting, increased aspartate aminotransferase level, and constipation. For those given Mec-V plus nivolumab (n = 25), the most common TEAEs included decreased appetite, fatigue, anemia, nausea, constipation, peripheral neuropathy, vomiting, increased alanine and aspartate aminotransferase levels, diarrhea, headache, neutropenia, pain in the extremity, pruritus, COVID-19, hypokalemia, muscular weakness, and pyrexia.

Ten percent of patients experienced related AEs that ultimately led to discontinuation; 5 cases were due to grade 2 peripheral neuropathy, 1 case was due to grade 2 ileus, 1 was due to grade 1 fatigue, and 1 was due to grade 3 pancreatitis. Notably, no ocular toxicities nor cases of interstitial lung disease were reported, and no patients experienced related AEs that proved fatal.

“The observed safety profile of Mec-V as monotherapy, and in combination with anti–PD-1 antibody, was manageable and consistent with conditional binding of the AXL target restricted to the tumor microenvironment,” Mihaela Druta, MD, of Moffitt Cancer Center in Tampa, FL, and coauthors, concluded.

Disclosures: Druta disclosed affiliations with Adaptimmune, Cogent Biosciences, and Deciphera Pharmacueticals.

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: 2025 SITC Annual Meeting; November 5-9, 2025; National Harbor, MD. Abstract 523.
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, Inc. November 7, 2025. Accessed November 18, 2025. https://ir.bioatla.com/news-releases/news-release-details/bioatlas-mecbotamab-vedotin-mec-v-axl-targeting-adc-demonstrates