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Pilot report of an anti-PD-1/VEGF bispecific antibody for treating recurrent H3K27M-mutant diffuse midline gliomas
Li Yanchu1, Wang Hongbin1, Yuan Xiaoli1
1Head and Neck Ward of West China Hospital of Sichuan University, Chengdu, China.
Background:
H3K27M-mutant diffuse midline gliomas (DMGs) are highly aggressive, immunosuppressive tumors that are resistant to conventional therapies. Median overall survival is typically 8-11 months after diagnosis; fewer than 10% of patients survive beyond 2 years, and the 5-year survival rate is generally below 1%. Ivonescimab, a novel bispecific antibody that simultaneously targets PD-1 and VEGF, may help overcome this resistance by restoring T cell immunity and normalizing tumor vasculature. We report the first use of ivonescimab as salvage therapy for recurrent DMG.
Methods:
Two patients with recurrent H3K27M-mutant DMG who experienced rapid progression after standard first-line chemoradiotherapy received off-label ivonescimab (10 mg/kg) plus chemotherapy intravenously every 3 weeks for 5-6 cycles.
Results:
After only three cycles, MRI revealed marked tumor shrinkage and substantial improvement in Karnofsky Performance Status (KPS). At treatment completion, both patients achieved partial remission (PR, tumor volume decreased at 66.7% and 68.7%, respectively). Both patients maintained progression-free survival (PFS) of more than 8 months and overall survival (OS) of more than 16 months, and both were alive more than 10 months after recurrence. Furthermore, treatment was well tolerated, the most common adverse event was fatigue, hematology toxicity and nausea vomiting, and no grade 3 or higher adverse events were observed.
Conclusions:
These preliminary findings demonstrate the tolerability of concurrent anti-PD-1/VEGF bispecific antibody with chemotherapy for recurrent DMG, who do not fit for reRT, and suggests that combination therapy may offer survival benefit. However, larger and more rigorous studies are needed to validate these initial observations and to define the efficacy and safety of this strategy in the clinical management of DMG.
Insights
This study shows ivonescimab combined with chemotherapy is a tolerable salvage therapy for recurrent diffuse midline gliomas (DMGs), offering survival benefits. The treatment led to tumor shrinkage and improved patient outcomes in two cases.
Area of Science:
- Oncology
- Immunotherapy
- Neuro-oncology
Background:
- Diffuse midline gliomas (DMGs) with H3K27M mutation are aggressive, treatment-resistant, and immunosuppressive pediatric brain tumors.
- Standard therapies offer limited survival benefits, with median overall survival typically 8-11 months.
- Ivonescimab, a bispecific antibody targeting PD-1 and VEGF, shows potential to overcome resistance by enhancing anti-tumor immunity and normalizing tumor vasculature.
Purpose of the Study:
- To evaluate the safety and efficacy of ivonescimab combined with chemotherapy as a salvage treatment for recurrent H3K27M-mutant diffuse midline gliomas (DMGs).
- To assess the impact of this combination therapy on tumor response, progression-free survival (PFS), and overall survival (OS) in patients ineligible for re-irradiation.
Main Methods:
- Two patients with recurrent H3K27M-mutant DMG received off-label ivonescimab (10 mg/kg) plus chemotherapy every 3 weeks for 5-6 cycles.
- Treatment was administered intravenously as salvage therapy after progression on standard first-line chemoradiotherapy.
Main Results:
- Marked tumor shrinkage and improved Karnofsky Performance Status (KPS) were observed after three cycles.
- Both patients achieved partial remission (PR) with tumor volume reductions of 66.7% and 68.7% at treatment completion.
- Progression-free survival (PFS) exceeded 8 months and overall survival (OS) exceeded 16 months, with both patients alive over 10 months post-recurrence.
- The combination therapy was well-tolerated, with fatigue, hematologic toxicity, and nausea/vomiting as the most common adverse events; no grade 3 or higher events occurred.
Conclusions:
- Concurrent anti-PD-1/VEGF bispecific antibody with chemotherapy is a tolerable salvage strategy for recurrent DMG patients unsuitable for re-irradiation.
- This combination therapy suggests a potential survival benefit for recurrent DMG.
- Larger studies are required to confirm these preliminary findings and establish the efficacy and safety of this approach in clinical practice.
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