Editor’s Note: At the recent “Yangtze River Academic Breast Cancer Mid-Year Exchange Conference & CSOE Tumor Drug Clinical Research Committee Mid-Year Meeting & 2025 ASCO Debrief,” Professor Ting Li from Fudan University Shanghai Cancer Center delivered an insightful presentation on two key topics: advances in TROP2-targeted ADC therapy for metastatic triple-negative breast cancer (mTNBC) and lessons learned from the Fudan ABC study regarding the challenges and strengths of young investigators conducting investigator-initiated trials (IITs).Oncology Frontier invited Professor Li for an in-depth interview to discuss major research updates on TROP2 ADCs in the treatment of mTNBC presented at ASCO 2025 and their clinical implications, as well as to share practical advice for young physicians undertaking IIT research.
Oncology Frontier: Could you share the latest developments in TROP2-targeted ADC therapy for mTNBC? What impact might these findings have on treatment strategies for this patient group?
Professor Ting Li: Triple-negative breast cancer (TNBC) remains one of the breast cancer subtypes with the poorest prognosis. As diagnostic and therapeutic technologies advance, immunotherapy and antibody-drug conjugates (ADCs) have opened new treatment avenues for TNBC. Several TROP2-targeted ADC studies, including both neoadjuvant and advanced-stage data, were presented at the recent ASCO 2025 Annual Meeting. Here, I’d like to focus on two key studies in advanced TNBC: ASCENT-04 and OptiTROP-Breast05.
The most notable is the ASCENT-04 trial—a global, multicenter, open-label, randomized phase III study evaluating sacituzumab govitecan (SG) plus pembrolizumab versus chemotherapy plus pembrolizumab as first-line treatment in PD-L1–positive (CPS ≥10) patients with unresectable locally advanced or metastatic TNBC who had not received prior systemic therapy. A total of 443 patients were randomized 1:1. Results showed a 35% reduction in the risk of progression or death in the SG-pembrolizumab arm compared with chemotherapy-pembrolizumab (11.2 vs 7.8 months; HR 0.65, 95% CI 0.51–0.84; P = 0.0009). Although overall survival (OS) data are not yet mature, early trends are promising. SG plus pembrolizumab demonstrated higher objective response rates (ORR) (60% vs 53%) and longer median duration of response (DoR) (16.5 vs 9.2 months). Safety profiles were consistent with previous findings, with a notably lower treatment-related discontinuation rate compared to chemotherapy (12% vs 31%). Importantly, the trial allowed crossover; 81% of patients in the control group received SG upon progression, which may affect the interpretation of OS outcomes.
ASCENT-04 is the first phase III trial to confirm that ADC plus immunotherapy can be used as a first-line regimen in TNBC, offering a new treatment option.
Another key study is the OptiTROP-Breast05 phase II single-arm trial, presented orally at ASCO by Professor Yongmei Yin of Jiangsu Province Hospital. This trial investigated the use of lorvotuzumab mertansine (RC88) as first-line therapy in patients with unresectable locally advanced or metastatic TNBC. Among the 41 patients enrolled, with a median follow-up of 18.6 months, the ORR reached 70.7%, DCR 92.7%, and median PFS was 13.4 months. Notably, even in patients with PD-L1 CPS <10, the ORR was 71.9% and median PFS 13.1 months. No treatment-related deaths, neurotoxicity, or interstitial lung disease were observed.
These findings suggest that the first-line treatment landscape for TNBC may evolve significantly. However, more mature OS data are still needed. Meanwhile, ASCENT-04 also raises several unresolved clinical questions—such as how to select treatment for patients who have already received immunotherapy in the neoadjuvant setting, and how to sequence among multiple ADC options to optimize therapeutic strategies.
Oncology Frontier: In your presentation at this year’s conference, you spoke on “Reflections from the Fudan ABC Study: Challenges and Strengths for Young Physicians Conducting IIT Research.” Could you share the main challenges young investigators face in conducting IITs? How do these challenges manifest across different stages of the research process?
Professor Ting Li: Young physicians indeed face multiple challenges when undertaking investigator-initiated trials (IITs). One of the major hurdles is the dual pressure of clinical responsibilities and research demands. Given the limited time for basic research, IITs often become an essential pathway for young doctors to publish and apply for research grants. The biggest challenge during the design phase is carving out time for study planning amid a heavy clinical workload. From our experience, one effective approach is to collaborate with fellow junior colleagues by sharing data and co-authoring papers.
During the implementation phase, data management becomes another significant obstacle. Unlike industry-sponsored trials (ISTs), IITs typically lack dedicated data management staff and must rely on the support of research nurses and clinical research coordinators (CRCs). In terms of quality control, IITs require the investigator to take greater responsibility for oversight, with support from periodic institutional audits. This demands a high degree of self-discipline and initiative from the investigator.
Most importantly, in the topic selection phase, young doctors must identify clinically meaningful research questions. A well-designed IIT should address gaps in current clinical guidelines or evidence-based practices. This calls for sharp clinical observation and critical thinking in day-to-day work.
Oncology Frontier: What advice or insights would you offer to young physicians planning to conduct IITs in the future? In terms of topic selection, team collaboration, and resource acquisition, what key areas should they focus on?
Professor Ting Li: Young doctors have unique strengths when conducting IITs. Being on the clinical frontlines, they are well-positioned to identify pressing issues that arise in real-world practice. Unlike industry-sponsored trials (ISTs), IITs focus more on addressing unmet clinical needs rather than commercial objectives, which often gives the findings greater clinical relevance.
For topic selection, I encourage young investigators to develop the habit of reflecting on and documenting challenging clinical questions. Staying up to date with international conferences and literature is also important for understanding what has been solved and what gaps remain in the field. A strong research question should be innovative, feasible, and clinically meaningful.
In terms of teamwork, I recommend building interdisciplinary teams to leverage the strengths of different experts. As for resource acquisition, young researchers should actively apply for institutional or society-funded grants and make full use of existing clinical data and sample resources. Above all, maintaining research integrity is essential—ensuring the quality of the study and the authenticity of the data.
Professor Ting Li
Fudan University Shanghai Cancer Center
Associate Chief Physician
