On March 26, 2025 Vaximm AG, a subsidiary of OSR Holdings, Inc. and a pioneering biotechnology company focused on developing innovative immunotherapies, reported final data from the successful conclusion of its open-label Phase 2a clinical trial assessing the safety and tolerability of VXM01, an investigational oral anti-VEGFR-2 vaccine, in combination with avelumab (PD-L1 inhibitor) in patients with recurrent glioblastoma (GBM). The trial was part of a collaboration with Merck KGaA, Darmstadt, Germany (Press release, Vaximm, MAR 26, 2025, View Source [SID1234651485]).
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Key results and observations:
The VXM01-avelumab combination therapy was generally well-tolerated, with the majority of safety events being mild to moderate in severity. These safety and tolerability data are in-line with previously reported data on avelumab alone with no additional safety signals for the combination of VXM01 and avelumab.
No serious adverse events (SAEs) were attributed to VXM01, while 9 of 11 (81.8%) were related to the target disease, underscoring the well manageable safety profile of this combination therapy in a frail patient population.
The non-resected patient cohort showed a 12.0% objective response rate (ORR). 12.0% of these patients showed a partial remission and 4.0% had stable disease. This suggests that, with further investigation, VXM01 in combination with PD-L1 inhibition (e.g. avelumab) could offer meaningful clinical benefit for this challenging patient population. In resected patients, the overall survival (OS) ranged from 2.2 to 46.5 months, highlighting the variability in response and the need for additional studies to determine optimal treatment regimens for specific subgroups of GBM patients.
Despite the small size of this open-label trial (n=25), the observed median time to progression of 2.7 months (95% CI: 2.7 – 2.7, range 0.3 – 22.1 months), and median OS of 11.1 months (95% CI: 8.5 – 16.3, range 3.8- 38.2 months), are encouraging initial results in the context of prognosis for patients with recurrent glioblastoma, reported to have a median PFS of 1.5 to 6 months and median OS of 2 to 9 months.(Birzu et al. 2020)
Decreased tumor size was observed in responding patients independent of tumor size at baseline, supporting the expectation that VXM01 vaccine treatment may be effective in patients with larger sized tumors as well as patients with early-stage cancer or very small tumors.
Exploratory biomarker investigations identified potential predictive and pharmacodynamic biomarkers of a VXM01-mediated tumor response
Moving Forward:
The reported safety and tolerability data, together with early indications for the potential relevance of a VXM01dependent, VEGFR-2 specific immune response in GBM therapy warrant further study.
"The completion of this Phase 2a study is a significant milestone for Vaximm AG, as it provides strong evidence that VXM01, in combination with avelumab is generally well-tolerated in patients with recurrent glioblastoma," said Dr. Constance Hoefer, CEO of Vaximm AG. "We are encouraged by these early results and the potential to improve outcomes for patients with this aggressive cancer. We remain committed to advancing VXM01 as a key therapeutic candidate for the treatment of glioblastoma, other cancers and other diseases where VXM01 may have positive impact on treatment outcomes"
About VXM01:
VXM01 is an oral T-cell immunotherapy that is designed to activate T-cells to attack the tumor vasculature and, in several tumor types, attack cancer cells directly. It is based on a live attenuated, safe, orally available bacterial vaccine strain, which is modified to carry vascular endothelial growth factor receptor-2 (VEGFR2) as the target gene. VXM01 stimulates the patient’s immune system to activate VEGFR2-specific, cytotoxic T-cells (so-called killer cells). These immune killer cells then actively destroy cells in the tumor vasculature, leading to an increased infiltration of various immune cells into the tumor. In several tumor types, including brain cancer, VEGFR2 is highly over-expressed on the cancer cells themselves. In preclinical studies, a murine analog VXM01 vaccine showed broad anti-tumor activity in different tumor types. This activity was linked to a VEGFR2-specific T-cell response and was accompanied by the destruction of the tumor vasculature and increased immune cell infiltration. In a Phase I double-blind, randomized, placebo-controlled study in 71 patients with advanced pancreatic cancer, VXM01 appeared to be safe and well tolerated and led to the activation of VEGFR2-specific cytotoxic T-cells, which was associated with significantly improved patient survival. Clinical activity in terms of objective responses and survival has been observed in recurrent glioblastoma.