Editor’s Note: Small cell lung cancer (SCLC), often referred to as the “king of lung cancers,” has seen little change in its first-line treatment over the past 30 years, with the EP regimen (etoposide plus cisplatin) remaining the backbone. Although recent advances in immuno-chemotherapy have brought survival benefits, long-term outcomes for patients remain limited.At the ongoing 2025 ASCO Annual Meeting, Professor Yan Huang from Sun Yat-sen University Cancer Center delivered an oral presentation (Abstract #3002) on the results of a Phase I study of the bispecific ADC agent BL-B01D1 in SCLC patients who had failed prior standard therapies. The drug, which targets both EGFR and HER3, demonstrated a confirmed objective response rate (ORR) of 75% and a median overall survival (OS) of 15.1 months in patients previously treated with immune-chemotherapy. These promising findings provide a potential new therapeutic option for this highly aggressive and difficult-to-treat cancer. Oncology Frontier invited Prof. Huang to share deeper insights into the clinical value and future applications of this novel agent.
Oncology Frontier: First of all, congratulations to you and your team on being selected for an oral presentation at ASCO. This Phase I study has yielded encouraging results in SCLC patients. Could you briefly summarize the key findings of this trial? Based on these results, what clinical research directions do you believe should be prioritized moving forward, and what potential impact might this have on clinical practice?
Prof. Yan Huang, Sun Yat-sen University Cancer Center: Thank you. It’s a great pleasure to share the results of our study with colleagues here at ASCO. This research focused on the Phase I clinical data of the bispecific ADC BL-B01D1 in the SCLC cohort. The agent is a bispecific antibody–drug conjugate targeting both HER3 and EGFR, with the payload being a topoisomerase I inhibitor, Ed-04.
Looking back, Professor Li Zhang first reported early Phase I data on BL-B01D1 at the 2023 ASCO meeting, focusing on patients with locally advanced or metastatic solid tumors. The current oral presentation specifically highlights the drug’s application in small cell lung cancer (SCLC). As we know, SCLC is often referred to as the “king of lung cancers,” and over the past three decades, the standard first-line treatment has remained centered around the EP regimen (cisplatin plus etoposide). While recent advances with EP combined with immunotherapy have brought some progress, long-term survival remains limited.
The most clinically meaningful data in our current study come from the second-line treatment cohort. Among patients who progressed following chemo-immunotherapy, BL-B01D1 demonstrated promising efficacy. The median overall survival (OS) reached 15 months, which represents a substantial improvement over historical benchmarks. In addition, the confirmed objective response rate (ORR) was 75%, significantly higher than the 20%–40% typically seen with standard second-line chemotherapy. I believe these compelling results were a key factor in the study being selected for oral presentation.
It is worth noting that the development pathway of BL-B01D1 offers valuable insights. In addition to the SCLC cohort discussed here, Professor Yunpeng Yang also presented findings from a parallel cohort evaluating BL-B01D1 in non-small cell lung cancer (NSCLC) patients with rare targets (Abstract #3001). The fact that two distinct cohorts from the same Phase I trial were selected for oral presentations at ASCO highlights both the drug’s innovative potential and the strong execution of the clinical research teams.
In my view, the success of a clinical study depends on the synergy of three key elements: innovative drug design, rigorous trial conduct and data quality control, and optimized development efficiency. When these components work in harmony, they can significantly accelerate the delivery of truly novel therapies to patients in need.
Oncology Frontier: Compared to traditional chemotherapy, what are the key mechanistic advantages of BL-B01D1 as an antibody–drug conjugate (ADC) targeting EGFR and HER3 in the context of precision therapy for SCLC?
Prof. Yan Huang, Sun Yat-sen University Cancer Center: The treatment landscape of SCLC is quite distinct. Apart from a few rare targets such as DLL3, SCLC remains largely a chemotherapy-dominated disease—markedly different from NSCLC, where defined oncogenic drivers like EGFR, ALK, and MET have paved the way for targeted therapies.
From current data, BL-B01D1 shows promising value in both the second-line setting and in patients who have failed standard therapies. I believe its clinical efficacy stems from its unique bispecific ADC design. On one hand, its targets—EGFR and HER3—are commonly overexpressed in SCLC, enabling the drug to precisely home in on tumor cells. On the other hand, the ADC’s novel linker structure and optimized payload significantly enhance intracellular drug delivery while minimizing peripheral toxicity.
This mechanism effectively breaks the traditional trade-off between treatment intensity and toxicity that we often face with chemotherapy. Patients can maintain potent anti-tumor activity while experiencing improved tolerability. For chemotherapy-sensitive SCLC, achieving sustained and stable long-term treatment may ultimately translate into meaningful survival benefits.
Oncology Frontier: BL-B01D1 has already demonstrated potential in other solid tumors. Based on its promising results in SCLC, how would you assess its future application prospects in oncology?
Prof. Yan Huang, Sun Yat-sen University Cancer Center: The core advantage of BL-B01D1 as a bispecific ADC lies in its precise targeting capability. The dual-target design—EGFR and HER3—enables enhanced efficacy in tumors with high expression of these markers, such as urothelial carcinoma and breast cancer. At the same time, ADCs deliver cytotoxic payloads directly to tumor cells, overcoming the dose limitations of traditional chemotherapy and enabling more durable treatment responses.
There are two key challenges that must still be addressed in ADC development. First, most current ADCs rely on a single cytotoxic payload—such as topoisomerase inhibitors—whereas standard treatments for solid tumors, including lung cancer, typically involve combination regimens (e.g., platinum-based doublet chemotherapy). A major future direction is to explore how classical agents like platinum compounds could be integrated into ADC platforms, potentially moving their use from late-line to front-line settings.
Second, toxicity management must continue to be improved. While the present study demonstrated manageable safety, hematologic toxicities were still observed in a notable proportion of patients. Moving forward, ADCs should aim to reduce systemic toxicity by refining linker technologies or modifying payload structures—while preserving therapeutic efficacy.
In addition, we must continue to explore novel targets, more potent payloads, and develop treatment strategies for patients who develop resistance to ADCs. These efforts will be crucial in fully realizing the clinical potential of this class of therapies.
Reference: Yan Huang, Li Zhang, Yuxiang Ma, et al. Phase I study of iza-bren (BL-B01D1), an EGFR x HER3 bispecific antibody-drug conjugate (ADC), in patients with locally advanced or metastatic small cell lung cancer (SCLC). ASCO 2025; Abstract 3002.
MD, PhD, Chief Physician, Doctoral Supervisor
Director of Medical Oncology, Sun Yat-sen University Cancer Center
Academic and Professional Appointments:
- Vice Chair, Committee on Cancer Rehabilitation and Palliative Care, Chinese Anti-Cancer Association
- Executive Member, Committee on Supportive and Rehabilitative Oncology, Chinese Society of Clinical Oncology (CSCO)
- Executive Member, Committee on Geriatric Oncology, CSCO
- Chair, Committee on Cancer Rehabilitation and Palliative Care, Guangdong Anti-Cancer Association
- Vice Chair, Committee on Chemotherapy, Guangdong Anti-Cancer Association
- Vice Chair, Committee on Precision Medicine, Guangdong Clinical Medicine Association
- Vice Chair, Committee on Precision Treatment and Clinical Research in Lung Cancer, Guangdong Clinical Medicine Association
