Editor's Note: The 2024 European Society for Medical Oncology (ESMO) Congress took place from September 13 to 17 in Barcelona, Spain. As one of the largest and most prestigious clinical oncology conferences in the world, it showcased numerous cutting-edge research findings, driving global advancements in oncology. In the field of breast cancer, Dr. Xiaojia Wang from Zhejiang Cancer Hospital presented a study on first-line treatment for advanced triple-negative breast cancer (TNBC) using a combination of two immunotherapy drugs and chemotherapy. The study, conducted alongside Professor Quchang Ouyang from Hunan Cancer Hospital, highlighted the promising outcomes of combining ivonescimab, a dual PD-1/VEGF inhibitor, with chemotherapy. This research was selected for oral presentation (#347MO) at the ESMO Congress, showcasing the innovation and research achievements of Chinese scientists.
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Oncology Frontier: Your research was selected for an oral presentation at this year’s ESMO conference. Could you briefly introduce the background of this study? Why was ivonescimab chosen as a new treatment strategy for triple-negative breast cancer (TNBC), and why was it combined with chemotherapy?
Dr. Xiaojia Wang: This research, co-led by Professor Quchang Ouyang from Hunan Cancer Hospital and myself, explored the efficacy of ivonescimab, a PD-1/VEGF bispecific antibody developed by Akeso Biopharma, in TNBC. Blocking both PD-1 and VEGF pathways creates a synergistic effect, giving this drug an enhanced antitumor response at the mechanistic level.
In TNBC, clinical treatment strategies have shifted from standard first-line chemotherapy to targeted therapies. For example, BRCA mutation patients can benefit from PARP inhibitors, and prior strategies combining anti-angiogenic agents with chemotherapy have also shown promise. However, despite satisfactory outcomes, some patients experienced intolerable side effects, and overall survival (OS) results were not positive, limiting the success of these regimens. Nevertheless, in real-world clinical practice, some patients with TNBC continue to use taxanes combined with bevacizumab, an anti-angiogenic drug, and achieve reasonable results.
Today, immunotherapy combined with chemotherapy has become a first-line treatment option for TNBC. For instance, the FUTURE-C-PLUS study, led by Professor Zhi-min Shao, demonstrated that immunotherapy combined with chemotherapy and anti-angiogenic agents resulted in high efficacy. Based on this, we believed that ivonescimab, which blocks both PD-1 and VEGF, combined with chemotherapy (either paclitaxel or nab-paclitaxel), could yield similarly promising outcomes. As an exploratory Phase II study, we planned to enroll 30 patients to preliminarily assess the efficacy of this treatment regimen.
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Oncology Frontier: Could you elaborate on the mechanism by which ivonescimab targets both PD-1 and VEGF pathways simultaneously and how this synergy provides powerful therapeutic effects for TNBC patients?
Dr. Xiaojia Wang: Ivonescimab simultaneously binds to PD-1 and VEGF, blocking immune signaling pathways while also inhibiting angiogenesis. Previous studies have already observed the synergistic effects of immunotherapy combined with anti-angiogenic agents, and the unique tailing effect of immunotherapy further enhances the efficacy of this dual blockade. By targeting these pathways, ivonescimab provides a potent therapeutic option for TNBC. Additionally, antibody-drug conjugates (ADC) combined with immunotherapy or anti-angiogenic drugs have shown strong anti-tumor activity and good synergy, further supporting the rationale behind the design of this study.
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Oncology Frontier: The study results showed a significant objective response rate (ORR) with ivonescimab combined with chemotherapy, particularly in the PD-L1 CPS ≥ 10 subgroup. Could you interpret these results and explain how they enhance our understanding of the immune microenvironment in TNBC?
Dr. Xiaojia Wang: As of March 31, 2024, 30 patients had been enrolled in the study, with 29 undergoing at least one efficacy assessment. The ORR was 72.4%. Notably, 80% of the enrolled patients had a CPS (combined positive score) < 10, and many even had a CPS < 1, which is typically a group less responsive to immunotherapy. However, the results demonstrated excellent efficacy in these patients, suggesting that the treatment may be acting through alterations in the tumor microenvironment to produce synergistic effects. Baseline analysis showed that all enrolled patients had failed prior anthracycline and taxane treatments, with 25% experiencing visceral metastases. Despite this, the regimen showed significant efficacy in these populations. For patients with CPS > 20, the data is still immature, and the PFS (progression-free survival) data for patients with CPS > 1 after a follow-up of 7.2 months is also not yet mature, but we anticipate better outcomes in the near future.
In terms of safety, the main adverse effects were bone marrow suppression or hepatotoxicity due to taxane chemotherapy. We did not observe any significant adverse reactions typically associated with anti-angiogenic or immunotherapy treatments, and the safety profile exceeded expectations.
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Oncology Frontier: Based on the current findings, what are your future expectations for ivonescimab in the treatment of TNBC? Are there plans for further clinical trials to validate and solidify these findings?
Dr. Xiaojia Wang: We plan to design and conduct a Phase III clinical trial for ivonescimab, hoping to replicate the results of the Phase II study. If successful, ivonescimab combined with taxane chemotherapy will likely become the new standard first-line treatment for TNBC.
Dr. Xiaojia Wang
Affiliated Cancer Hospital of the Chinese Academy of Sciences/Zhejiang Cancer Hospital
Chief Physician, Department of Breast Oncology
PhD and Postdoctoral Supervisor
Deputy Director, Zhejiang Provincial Cancer Intelligent Diagnosis and Molecular Technology Research Center
Vice Chair, CSCO Breast Cancer Expert Committee
Standing Committee Member, Breast Cancer Division, Chinese Anti-Cancer Association
Standing Committee Member, Medical Ethics Committee
Member, Cardio-Oncology Group, Cardiovascular Disease Division, Chinese Medical Association
Vice President, Yangtze River Delta Tumor Specialty Alliance
Chair, Zhejiang Provincial Breast Cancer Quality Control Expert Committee
Chair, Oncology Division, Zhejiang Medical Association; Vice Chair, Pain Division
Chair, Breast Cancer Division, Zhejiang Anti-Cancer Association; Former Chair, Oncology Division
Vice President, Zhejiang Immunology Association
Vice President, Zhejiang Translational Medicine Association; Chair, Precision Medicine Division
