Dual PD-1 and VEGF Targeting in a Single Treatment
Ivonescimab is a newer form of cancer immunotherapy that simultaneously targets PD-1 and VEGF, combining immune activation with inhibition of tumor blood-vessel signaling.
PD-1 is an immune checkpoint that cancer cells can use to reduce T-cell activity. Blocking PD-1 can restore the immune system’s ability to recognize and attack cancer. VEGF, meanwhile, promotes the development of blood vessels that supply tumors and can also contribute to an immune-suppressive tumor environment.
By addressing both pathways at the same time, ivonescimab is designed to improve immune activity within the tumor while also limiting VEGF-driven tumor support.
One important treatment setting is previously untreated advanced non-small cell lung cancer with PD-L1 expression.
In the phase III HARMONi-2 trial conducted in China, ivonescimab was directly compared with pembrolizumab, one of the most widely used PD-1 immunotherapies.
Median progression-free survival was 11.1 months with ivonescimab versus 5.8 months with pembrolizumab. The benefit was observed both in patients with PD-L1 tumor proportion scores of 1–49% and in those with PD-L1 expression of 50% or higher.
This makes the treatment especially relevant for patients whose tumors are PD-L1 positive but do not carry another dominant actionable driver mutation requiring targeted therapy.
Treatment generally involves intravenous administration at scheduled intervals, with imaging performed periodically to determine whether the cancer is shrinking, stable, or progressing.
Potential adverse effects can include immune-related inflammation, hypertension, proteinuria and other effects associated with VEGF inhibition, as well as more general immunotherapy-related complications affecting organs such as the lungs, liver, thyroid or gastrointestinal tract.
Patients may be considered for this approach when they have:
- Advanced or metastatic non-small cell lung cancer
- Positive PD-L1 expression
- No more appropriate targeted therapy based on a dominant driver mutation
- Adequate organ and cardiovascular function
Ivonescimab represents an important example of a newer treatment strategy in which immune checkpoint blockade and anti-angiogenic therapy are integrated into one bispecific antibody.
