Vaximm AG, a subsidiary of OSR Holdings, Inc., has announced encouraging results from its Phase 2a clinical trial evaluating the combination of VXM01 and avelumab in patients with recurrent glioblastoma (GBM). The open-label study, conducted in collaboration with Merck KGaA, assessed the safety and tolerability of VXM01, an investigational oral anti-VEGFR-2 vaccine, when used alongside avelumab, a PD-L1 inhibitor.
Safety Profile Supports Further Development
The combination therapy demonstrated a favorable safety profile, with most adverse events being mild to moderate in severity. Notably, no serious adverse events (SAEs) were attributed to VXM01, while 81.8% of SAEs were related to the underlying disease. This safety profile aligns with previously reported data on avelumab monotherapy, with no additional safety signals observed from the combination.
"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."
Promising Efficacy Signals
Despite the small sample size (n=25), the trial yielded encouraging efficacy data. In the non-resected patient cohort, a 12.0% objective response rate was observed, with 12.0% of patients achieving partial remission and 4.0% experiencing stable disease.
The median time to progression was 2.7 months (95% CI: 2.7–2.7, range 0.3-22.1 months), while the median overall survival reached 11.1 months (95% CI: 8.5–16.3, range 3.8-38.2 months). These results are particularly noteworthy given that recurrent glioblastoma typically has a median progression-free survival of 1.5 to 6 months and median overall survival of just 2 to 9 months.
In resected patients, overall survival ranged from 2.2 to 46.5 months, highlighting significant variability in response and suggesting the need for further studies to identify optimal treatment approaches for specific GBM patient subgroups.
Tumor Response Independent of Baseline Size
An important finding from the trial was that decreased tumor size was observed in responding patients regardless of tumor size at baseline. This suggests that VXM01 vaccine treatment may be effective across a spectrum of disease presentations, from early-stage cancer with small tumors to more advanced disease with larger tumor burden.
Mechanism of Action and Biomarker Development
VXM01 represents an innovative approach to cancer immunotherapy. The oral T-cell immunotherapy is designed to activate T-cells to attack tumor vasculature and, in certain tumor types including brain cancer, to directly target cancer cells. The vaccine is based on a live attenuated, orally available bacterial strain modified to carry vascular endothelial growth factor receptor-2 (VEGFR2) as the target gene.
The mechanism involves stimulating the patient's immune system to activate VEGFR2-specific cytotoxic T-cells, which then destroy cells in the tumor vasculature. This leads to increased infiltration of various immune cells into the tumor. In glioblastoma and several other cancers, VEGFR2 is highly overexpressed on the cancer cells themselves, making it a relevant target.
Exploratory biomarker investigations in the trial identified potential predictive and pharmacodynamic biomarkers of VXM01-mediated tumor response, which could help guide patient selection in future studies.
Previous Clinical Experience
This is not the first clinical evaluation of VXM01. In a previous Phase I double-blind, randomized, placebo-controlled study involving 71 patients with advanced pancreatic cancer, VXM01 appeared safe and well-tolerated. That study demonstrated activation of VEGFR2-specific cytotoxic T-cells, which was associated with significantly improved patient survival.
Path Forward
The safety and tolerability data from this Phase 2a trial, combined with early indications of the potential relevance of a VXM01-dependent, VEGFR-2 specific immune response in GBM therapy, support further investigation of this approach.
Vaximm remains committed to advancing VXM01 as a key therapeutic candidate for glioblastoma and potentially other cancers where the immunotherapy may positively impact treatment outcomes. The company's innovative approach aims to address the significant unmet needs of patients suffering from these aggressive malignancies.
About the Companies
Vaximm AG is a pioneering biotechnology company focused on developing innovative immunotherapies. Through novel approaches, Vaximm aims to unlock the potential of cancer vaccines and immuno-oncology therapies.
The company is a subsidiary of OSR Holdings, Inc. (NASDAQ: OSRH), a global healthcare company dedicated to advancing healthcare outcomes. OSR's portfolio includes Vaximm (developing oral immunotherapies for cancer), Darnatein (developing design-augmented biologics for age-related and degenerative diseases), and RMC (neurovascular intervention medical device and systems distribution in Korea).
