Editor’s Note: At the recent San Antonio Breast Cancer Symposium (SABCS), Dr. Jiong Wu from Fudan University Shanghai Cancer Center and his team presented several significant research findings, offering new insights into breast cancer treatment.

During the “Poster Spotlight 3” session on December 11, Professor Wu showcased the study on the combination of PM8002/BNT327 with nab-paclitaxel for the treatment of locally advanced or metastatic triple-negative breast cancer (TNBC) (Abstract No.: PS3-08). The results revealed that this combination therapy demonstrated remarkable anti-tumor activity, independent of PD-L1 expression levels, bringing new hope for TNBC treatment.

Oncology Frontier had the opportunity to speak with Professor Wu at SABCS. In addition, Professor Wu shared insights into the latest developments in treatments for HR+/HER2- and HER2-positive breast cancer, reflecting the current research trends and hot topics in breast cancer therapies.

Oncology Frontier: Your team presented several studies at this year’s SABCS. Could you briefly introduce these research findings?

Dr. Jiong Wu: Indeed, more and more researchers are sharing their findings at the San Antonio conference through presentations and poster discussions. Our team contributed three key studies during the poster sessions at this conference.

On December 11, I presented a poster titled “PS3-08: Interim Overall Survival of Patients with Locally Advanced or Metastatic Triple-Negative Breast Cancer Treated with First-Line PM8002/BNT327 in Combination with Nab-Paclitaxel in a Phase Ib/II Study” and participated in the discussion.

This study explored the interim overall survival of patients receiving PM8002/BNT327—a PD-L1/VEGF bispecific antibody—combined with nab-paclitaxel as first-line treatment for locally advanced or metastatic TNBC. The initial results of this study were presented at the 2023 SABCS. With extended treatment duration, the patient data has matured.

At this SABCS, the latest results showed that as of September 13, 2024, the median follow-up period was 18.1 months (95% CI: 16.9–19.7), and the median treatment duration was 10.0 months (range: 2.0–22.0), with 9 out of 42 patients still receiving treatment. The confirmed objective response rate (cORR) was 73.8%, and the disease control rate (DCR) was 95.2%.

The median time to response (TTR) was 1.9 months (95% CI: 1.8–2.0), and the median duration of response (DOR) was 11.7 months (95% CI: 7.2–17.3). The mature median progression-free survival (PFS) in the intention-to-treat (ITT) population was 13.5 months (95% CI: 9.4–18.1). The median overall survival (OS) has not yet been reached, with a 12-month OS rate of 80.8% (95% CI: 65.3–89.9), a 15-month OS rate of 78.1% (95% CI: 62.1–88.0), and a nearly mature 18-month OS rate of 72.2% (95% CI: 55.2–83.7).

PM8002/BNT327 is a bispecific antibody targeting PD-L1 and VEGF-A, combining immunomodulation with anti-angiogenesis to synergistically inhibit tumor progression. Mechanistically, it blocks immune signaling pathways while suppressing angiogenesis, improving the tumor microenvironment and enhancing the immune response of effector T cells from systemic circulation.

Because bispecific antibodies directly target tumor cells and remain localized in the tumor site, they offer a higher safety profile. We are hopeful that with longer follow-up, this therapy will show even more pronounced overall survival benefits, offering more treatment options for TNBC in the future.

Additionally, our team presented two more Poster Spotlight studies, led by two of my students. These studies focused on the immune effects during drug treatment, aiming to predict the efficacy of chemotherapy and immunotherapy in TNBC and HER2-positive breast cancer. This reflects our current research direction—optimizing systemic treatment approaches to better assess which patients will benefit most from targeted or systemic therapies.

Oncology Frontier: The findings from your PS3-08 study presented during the Poster Spotlight Sessions at SABCS demonstrated that the combination of PM8002/BNT327 with nab-paclitaxel shows strong anti-tumor activity regardless of PD-L1 status. What implications does this discovery have for future treatment strategies in TNBC?

Dr. Jiong Wu: Currently, first-line treatment for recurrent or metastatic breast cancer, especially TNBC, has entered an era of chemotherapy combined with immunotherapy. Although combining cytotoxic drugs with anti-angiogenic therapy has shown promising disease control in some patients, it often fails to provide a significant overall survival benefit and can cause severe adverse effects. Therefore, PD-L1 and VEGF have remained critical therapeutic targets.

PM8002/BNT327, as a bispecific antibody targeting PD-L1 and VEGF, brings new hope. During this SABCS Poster Spotlight 3 session, two studies focused on TNBC. In addition to my research on PM8002/BNT327 (Abstract No.: PS3-08), Professor Xiao Jia Wang presented research on Ivonescimab, a PD-1/VEGF bispecific antibody (Abstract No.: PS3-05). The difference between these two drugs lies in their targets—PD-L1 versus PD-1—but both demonstrated promising clinical outcomes through effective inhibition of the PD-(L)1 axis, regardless of PD-(L)1 expression levels.

In our study, among 42 patients, only 9 had a PD-L1 Combined Positive Score (CPS) ≥10, while 13 had CPS <1, and 16 had CPS between 1–10. Four patients were not tested. Across these groups, the treatment demonstrated consistent efficacy regardless of PD-L1 expression, reinforcing the importance of bispecific antibodies in blocking angiogenesis and modifying the tumor microenvironment to enhance immunotherapy outcomes. However, more preclinical data and studies are needed to further validate this mechanism, and ongoing research is addressing this.

Oncology Frontier: Several groundbreaking studies were presented at this SABCS. Could you share the research areas you focused on and the significant findings from these studies?

Dr. Jiong Wu: On the morning of December 11, during the General Session, several critical studies caught my attention. I’d like to discuss them from a stratified treatment perspective.

For HR+/HER2- breast cancer, the current standard for advanced HR+/HER2- breast cancer is endocrine therapy combined with CDK4/6 inhibitors as a first-line treatment. However, when disease progression occurs, overcoming drug resistance becomes essential. Resistance mechanisms often involve patient-specific mutations that lead to treatment failure. For example, estrogen receptor downregulators (SERDs), like fulvestrant, face challenges when ESR1 mutations emerge, necessitating higher doses to overcome resistance. Since increasing the dosage of first-generation drugs is limited, novel SERDs, particularly oral SERDs, are under active investigation.

The EMBER-3 study (Abstract No.: GS1-01) presented at this conference explored Imlunestrant, a SERD, both as monotherapy and in combination with abemaciclib for ER-positive, HER2-negative advanced breast cancer. The results showed that Imlunestrant significantly improved progression-free survival (PFS) in patients with ESR1 mutations compared to the standard of care. Moreover, combining Imlunestrant with abemaciclib yielded even better PFS outcomes than Imlunestrant alone. These findings are very exciting and provide strong evidence for future treatment strategies in this breast cancer subtype.

For HER2-positive breast cancer, I’d like to highlight two studies from Chinese researchers.

Academician Bing He Xu presented the final PFS data of the PHILA study, which showed that the median follow-up times for the PyroHT and HT groups were 35.7 months and 34.3 months, respectively. Investigator-assessed median PFS was 22.1 months for the PyroHT group versus 10.5 months for the HT group (HR = 0.44, 95% CI: 0.36–0.53; P < 0.0001), significantly outperforming the HT group. Although the OS data are not yet mature, they show a promising trend toward improved survival.

Professor Junjie Li, representing Professor Zhimin Shao’s team, reported findings from the FASCINATE-N study. This study utilized a precision platform to subtype breast cancer and design neoadjuvant treatment regimens for different breast cancer types. The SHR-A1811 study included three treatment groups: SHR-A1811 monotherapy, SHR-A1811 combined with pyrotinib, and the PCbHP regimen. Most enrolled patients had a high tumor burden, with tumors larger than 5 cm and 90% having positive lymph node status. Notably, the pathological complete response (pCR) rate in the SHR-A1811 monotherapy group reached 63%, which is highly encouraging. However, further research focusing on biomarkers is necessary to better identify patients who would benefit most from neoadjuvant anti-HER2 therapy.

Dr. Jiong Wu

Dr. Jiong Wu is the Executive Vice President of Fudan University Shanghai Cancer Center, Chief Physician, and Doctoral Supervisor. He also serves as the Director of the Clinical Trials Office, the Executive Director of the Integrated Breast Cancer Committee of the Chinese Anti-Cancer Association, and the Chairman of the 9th Breast Cancer Committee of the Chinese Anti-Cancer Association.

Additionally, he is the Vice Chairman of the Breast Surgery Committee of the Chinese Medical Doctor Association, Vice Chairman of the Oncology Committee of the Chinese Medical Doctor Association, a Standing Committee Member of the Oncology Branch of the Chinese Medical Association, the Chair-Elect of the Oncology Branch of the Shanghai Medical Association, and the Honorary Chairman of the Breast Cancer Branch of the Shanghai Anti-Cancer Association.