At the European Society for Medical Oncology Asia Congress 2024 (ESMO Asia 2024), Dr. Danbo Wang from Liaoning Cancer Hospital presented the latest findings from the DUBHE-C-204 study during the Gynecological Oncology Oral Abstracts session (Abstract No. 373O). Oncology Frontier had the privilege of interviewing Professor Wang on-site to discuss the study's key findings and share highlights from this year’s conference.

Oncology Frontier ：You presented the latest results of the DUBHE-C-204 study at ESMO Asia 2024. Could you share the background, key findings, and potential clinical implications for recurrent or metastatic cervical cancer (r/mCC)?

Dr. Danbo Wang: This is my second oral presentation of the DUBHE-C-204 study at an international conference—the first was at ESMO 2023. Being selected again for ESMO Asia highlights the significance of this study in the professional community.

The DUBHE-C-204 study investigates a novel therapy, Ipafricept-volrilotumab (a PD-1 and CTLA-4 combination antibody). Early-phase QL1706-102 trials demonstrated promising efficacy, which was further validated in the expanded DUBHE-C-206 study. Building on this, DUBHE-C-204 explored the efficacy and safety of the antibody in combination with chemotherapy ± bevacizumab as a first-line treatment for advanced or recurrent cervical cancer. A critical focus of the study was the safety of this multi-drug combination therapy.

The primary endpoint was safety, with interim data from 14 months published last year. This year, the 27-month follow-up data showed further improvement. Both the four-drug combination (Ipafricept-volrilotumab + chemotherapy + bevacizumab) and the three-drug combination (Ipafricept-volrilotumab + chemotherapy) demonstrated manageable safety profiles. Grade ≥3 treatment-related adverse events (TRAEs) occurred in 75% of patients, with hematological toxicity being the most common, primarily attributed to chemotherapy. Grade ≥3 immune-related adverse events (irAEs) were relatively low at 15%, mainly presenting as thyroid dysfunction or rash. Severe immune-related adverse events were rare, with no significant increase compared to monotherapy.

In terms of efficacy, the combination therapy achieved an objective response rate (ORR) of 81.0%, a disease control rate (DCR) of 98.3%, and a median progression-free survival (PFS) of 15.1 months. Median overall survival (OS) was not yet reached. These results exceeded our expectations. We look forward to larger Phase III trials to provide more robust data to confirm the efficacy of this combination in cervical cancer treatment.

Oncology Frontier ：Single-agent immune checkpoint inhibitors (ICIs) have already shown efficacy in r/mCC, with NCCN guidelines recommending PD-1 inhibitors plus chemotherapy ± bevacizumab for first-line treatment in PD-L1-positive advanced cervical cancer. How does dual-immunotherapy differ from single-agent immunotherapy?

Dr. Danbo Wang: Cervical cancer is considered an “immune hot tumor.” Previous successes with ICIs, such as those demonstrated in the KEYNOTE-158 and KEYNOTE-826 studies, have established immunotherapy as a viable option for cervical cancer. However, single-agent ICIs are generally effective only in PD-L1-positive patients.

NCCN guidelines recommend PD-1 inhibitors for PD-L1-positive patients, leaving PD-L1-negative patients without an immunotherapy option. Dual-immunotherapy offers the potential to benefit both PD-L1-positive and PD-L1-negative patients. In our study, the dual-immune combination improved PFS and ORR compared to historical data from single-agent therapies.

Oncology Frontier ：As a prominent academic event in the Asia-Pacific region, ESMO Asia showcased numerous cutting-edge findings and innovative treatments. What were your impressions of this year’s conference, and which gynecological oncology advancements stood out to you?

Dr. Danbo Wang: The ESMO Asia conference highlighted many promising results in gynecological oncology.

In ovarian cancer, antibody-drug conjugates (ADCs) remain a hot topic. This year, significant data were presented on ADC therapies, and there is growing interest in transforming “immune cold tumors” into “immune hot tumors” through combination therapies. The conference featured research exploring immunotherapy combined with chemotherapy and bevacizumab for ovarian cancer.

For endometrial cancer, immunotherapy has already shown success in microsatellite instability-high (MSI-H) or mismatch repair-deficient (dMMR) patient populations. New studies presented at ESMO Asia 2024 explored strategies for microsatellite-stable (pMMR) patients. Promising ADC targets, such as HER2 and TROP2, were also highlighted.

In cervical cancer, immunotherapy continues to dominate the field. Researchers are actively exploring various combination strategies, including immunotherapy with radiotherapy, dual-immunotherapy, bispecific antibodies, and combination antibodies. The DUBHE-C-204 study is a notable example of immunotherapy advancements presented at ESMO Asia. Additionally, many impactful ADC-related studies were shared during the conference.

Final Thoughts : The DUBHE-C-204 study provides valuable insights into the potential of dual-immunotherapy for cervical cancer, underscoring the need for further optimization and larger-scale trials to confirm its benefits. ESMO Asia 2024 has once again demonstrated its role as a platform for advancing innovation and collaboration in oncology research.

Dr. Danbo Wang

• Title: Distinguished Professor, Doctoral Advisor, Director of Gynecology Research, Liaoning Cancer Hospital
• Positions: Member, Standing Committee, Liaoning Provincial People’s Political Consultative Conference Deputy Director, Science, Education, Culture, and Health Committee Recipient of the State Council Special Allowance National Health Commission Outstanding Young and Middle-Aged Expert Liaoning Provincial Distinguished Expert Principal Investigator of 5 National Natural Science Foundation projects Author of over 100 publications

Professional Affiliations:

• Standing Committee Member, Gynecological Oncology Division, Chinese Medical Association
• Chair, Integrated Rehabilitation Committee for Gynecological Oncology, Chinese Anti-Cancer Association
• Vice Chair, Gynecological Oncology Division, CSCO
• Standing Committee Member, Tumor Prevention and Control Division, Chinese Preventive Medicine Association
• Standing Committee Member, Endoscopic Physicians Division, Chinese Medical Doctor Association
• Deputy Editor-in-Chief, Chinese Journal of Practical Gynecology and Obstetrics
• Vice President, Liaoning Medical Doctor Association
• Vice Chair, Liaoning Anti-Cancer Association