Journal of Hematology & Oncology | Clinical Progress of PD-(L)1×VEGF Bispecific Antibodies in Solid Tumors and Interpretation of ASCO 2026 Data

This study provides a novel bispecific antibody strategy for first-line treatment of lung cancer and various solid tumors, highlighting the need to focus on the construction of animal models for synergistic blockade of VEGF-A and immune checkpoints, as well as biomarker screening, in experimental design.

 

Literature Overview

This article, titled "PD-(L)1×VEGF bispecific antibodies in solid tumors: clinical trial updates from ASCO 2026," published in the Journal of Hematology & Oncology, systematically explores the latest clinical data on PD-(L)1 and VEGF bispecific antibodies in various solid tumors, particularly the survival benefits demonstrated by the HARMONi-6 trial in non-small cell lung cancer.

Background Knowledge

This study aims to address the core challenges in solid tumor treatment caused by abnormal angiogenesis, which leads to immune escape and drug penetration barriers. Currently, monotherapy with PD-1 or VEGF inhibitors often faces bottlenecks such as high resistance and efficacy plateaus, while combination therapy involves complex toxicity management. Bispecific antibodies, by simultaneously blocking the PD-1 and VEGF-A pathways with a single molecule, utilize synergistic binding effects to enhance immune cell infiltration and achieve vascular normalization, becoming a key entry point to break the current deadlock in tumor immunotherapy.

 

 

Research Methods and Experiments

The authors summarized data from multiple prospective clinical trials presented at the ASCO 2026 conference, including the randomized controlled Phase III HARMONi-6 trial and several Phase I/II exploratory studies. These studies evaluated the efficacy and safety of bispecific antibodies such as ivonescimab and pumitamig, either as monotherapy or in combination with chemotherapy, in human clinical trials validated by animal models of non-small cell lung cancer, small cell lung cancer, head and neck squamous cell carcinoma, and colorectal cancer.

Key evidence indicates that in treatment-naïve patients with advanced squamous non-small cell lung cancer, ivonescimab combined with chemotherapy significantly prolonged overall survival compared to tislelizumab combined with chemotherapy, without new safety signals. Furthermore, in refractory cancers such as small cell lung cancer and endometrial cancer, these agents demonstrated encouraging objective response rates, validating the efficacy of dual-target synergistic effects in complex tumor microenvironments.

Key Conclusions and Perspectives

• The HARMONi-6 trial confirmed that ivonescimab combined with chemotherapy is significantly superior to standard PD-1 inhibitors in the first-line treatment of squamous non-small cell lung cancer, with a median overall survival of 27.9 months, establishing a new efficacy benchmark for subsequent drug development.
• New bispecific antibodies such as SSGJ-707 and HB0025 have shown high objective response rates in non-small cell lung cancer and endometrial cancer, suggesting that different molecular configurations (e.g., IgG4 type or fusion protein type) possess clinical potential. This guides future experimental directions to focus on the impact of molecular structure on pharmacokinetics.
• In the neoadjuvant setting for small cell lung cancer and head and neck squamous cell carcinoma, ivonescimab combined with chemotherapy achieved a pathological complete response rate of up to 50%, indicating that this strategy can significantly improve surgical resection rates and providing an important direction for translational medicine research.
• Despite significant efficacy, VEGF-related toxicities (such as hypertension, proteinuria, and bleeding risks) require close monitoring, suggesting that future clinical monitoring must establish a specific safety assessment system for dual-pathway inhibition.

Research Significance and Prospects

This discovery will drive drug development to transition from single-target to dual-target synergistic blockade, holding breakthrough significance particularly for treatment strategies in "immune-cold" tumors. For clinical monitoring, more precise biomarkers are needed to predict immune activation effects and toxicity reactions following VEGF-A blockade. Additionally, these results provide a new paradigm for disease modeling, suggesting that when constructing humanized mouse models, both angiogenesis and immune checkpoint dual-regulation mechanisms should be simulated simultaneously to more accurately reflect clinical efficacy.

 

 

Conclusion

In summary, PD-(L)1×VEGF bispecific antibodies represent a new paradigm in solid tumor immunotherapy. The latest data from ASCO 2026 not only confirm their survival benefits in first-line non-small cell lung cancer but also demonstrate immense potential in refractory areas such as small cell lung cancer, colorectal cancer, and head and neck tumors. From laboratory mechanism validation to clinical translation, these agents effectively overcome the resistance bottlenecks of traditional therapies by synergistically blocking VEGF-A-mediated vascular abnormalities and PD-1-mediated immune suppression. Future research should focus on optimizing dosing sequences, exploring predictive biomarkers, and meticulously managing immune-related adverse events, thereby building a more precise and efficient care system for solid tumor patients and advancing tumor treatment from "prolonging survival" to "deep remission."

 

Zhao Wang, Chengcheng Guo, Xiaosi Yuan, Rui Zhang, and Zegeng Chen. PD-(L)1×VEGF bispecific antibodies in solid tumors: clinical trial updates from ASCO 2026. Journal of Hematology & Oncology.