Editor’s Note: With advances in technology and growing clinical experience, China’s development of antibody-drug conjugates (ADCs) has evolved from following international trends to driving innovation independently. A recent example is the phase I clinical trial of YL201—the world’s first B7-H3-targeted ADC for advanced solid tumors—led by Professors Li Zhang and Hongyun Zhao from Sun Yat-sen University Cancer Center. The results were published in Nature Medicine, one of the most respected medical journals worldwide, marking a new step in global recognition for domestically developed therapies.

Oncology Frontier invited Professors Zhang and Zhao to discuss the efficacy and safety of YL201 in cancers such as small cell lung cancer and nasopharyngeal carcinoma, and to share their perspectives on the drug’s future clinical potential.

01 | Oncology Frontier:

You’ve been deeply involved in lung cancer research for many years and have made significant contributions. Based on your clinical experience, could you share with us the current state and key challenges in the diagnosis and treatment of small cell lung cancer (SCLC)? Which areas are in urgent need of improvement?

Prof. Li Zhang:Lung cancer remains the leading cause of cancer-related deaths in China. Each year, there are approximately 1.06 million newly diagnosed cases in the country [1], which means that about two out of every five lung cancer patients worldwide are from China. This makes lung cancer a major threat to public health and life expectancy in the country.

Among lung cancers, small cell lung cancer (SCLC) accounts for about 15% of all cases [2]. It typically originates from neuroendocrine cells in the bronchial basal layer and is characterized by extremely rapid growth and a tendency to present as a systemic disease [2]. Because of this aggressive nature, surgery has limited effectiveness. In fact, early randomized controlled trials showed that patients who underwent surgery had even shorter survival times compared to those who received radiotherapy alone [3].

Therefore, surgery is generally not considered for SCLC patients—except in very early stages or rare cases where the diagnosis is made postoperatively. The rapid progression and high metastatic potential of SCLC result in poor overall prognosis. For patients with extensive-stage disease, most unfortunately die within two years. Even for those with limited-stage disease, only around 30% may achieve relatively long-term survival through concurrent chemoradiotherapy [4], while 70% do not receive effective treatment.

Overall, the five-year survival rate for SCLC is less than 10%, underscoring its aggressive nature. It remains one of the most life-threatening subtypes of lung cancer.

02 | Oncology Frontier:

With recent advances in ADC therapies, patients with small cell lung cancer now have new treatment options. Notably, a study on the novel ADC YL201 was recently published in Nature Medicine. As one of the corresponding authors, could you briefly introduce its efficacy and safety in SCLC treatment? What are the key takeaways for clinical practice?

Prof. Hongyun Zhao:This was an open-label phase I/Ib clinical trial of YL201, structured in two parts: a dose-escalation phase (phase I) and a dose-expansion phase (phase Ib). This design represents the current standard approach in the development of innovative therapies. The study, which included multiple tumor types, was recently published in Nature Medicine and reported data from 312 patients across 54 research centers [5].

During the trial, we observed that YL201 demonstrated significant therapeutic activity in small cell lung cancer (SCLC), nasopharyngeal carcinoma (NPC), and pulmonary lymphoepithelioma-like carcinoma (LELC). Particularly in SCLC patients who had received second-line or later treatment, YL201 achieved an objective response rate (ORR) of 63.9%, which is nearly three times higher than the historical ORR of around 20% for standard second-line therapies [5].

The strong responses seen in NPC and LELC were also reported internationally for the first time, offering new hope to clinical teams and patients alike. These findings not only validate YL201’s potential but also provide meaningful direction for future clinical research and practice.

YL201 is an antibody-drug conjugate (ADC) that functions similarly to chemotherapy targeting B7-H3. Its safety profile is generally consistent with other ADCs that use topoisomerase inhibitors as the cytotoxic payload. The most common adverse events were hematologic toxicities, including leukopenia, anemia, and neutropenia. The incidence of grade ≥3 treatment-related hematologic toxicities ranged from 13.8% to 31.7%, which aligns with findings from other studies [5].

Importantly, medical oncologists are highly experienced in managing chemotherapy-related toxicities, and with appropriate supportive care, many patients can be stabilized. The treatment discontinuation rate due to adverse events was relatively low at 5.4%, and dose reductions occurred in 17% of patients—both considered within acceptable limits.

Notably, interstitial lung disease (ILD)—a particular concern in ADC development—was observed at a low incidence of around 1% [5], suggesting that the risk of pulmonary toxicity with YL201 is low. Infusion-related reactions were also rare.

Overall, YL201 demonstrated a manageable safety profile, with relatively low rates of dose modification and treatment discontinuation due to adverse events. This large phase I study addressed both efficacy and safety questions that traditionally require separate phase I and II trials. As a result, we have already initiated two phase III clinical trials—one for small cell lung cancer and one for nasopharyngeal carcinoma.

While the phase I results have garnered significant attention, we believe that the clinical application of YL201 should ultimately be guided by the outcomes of the phase III trials. Based on current findings, however, the drug has the potential to influence clinical practice and may eventually be incorporated into treatment guidelines.

YL201 represents a significant step for China in the field of original drug innovation. Its global co-development model marks a shift from China being a participant in global oncology research to becoming a leader. If the results from the phase III trials are positive, YL201 could benefit cancer patients not only in China but around the world.

03 | Oncology Frontier:

We understand that B7-H3 is also expressed in nasopharyngeal carcinoma (NPC) and other solid tumors. Your team has been involved in research in this area for many years. Could you share the findings on how this new drug performs in NPC?

Prof. Li Zhang:Nasopharyngeal carcinoma (NPC) is a malignancy with distinct regional characteristics. In fact, it is the only cancer named after a geographic region—colleagues abroad often refer to NPC as the “Canton tumor,” with “Canton” referring to Guangdong. The disease shows a clear geographic pattern: it is most prevalent in southern China and is also seen at higher rates in areas of Southeast Asia and Africa located at similar latitudes.

In regions where Epstein-Barr virus (EBV) is endemic, early and repeated infections are associated with increased NPC risk. Genetic predisposition also plays a role, making NPC one of the more common cancers in southern China. While over 90% of the general population has been infected with EBV at some point, the link between EBV and NPC is not observed in non-endemic areas north of the Yangtze River, where the disease more closely resembles differentiated squamous cell carcinomas of the head and neck.

In the phase I clinical trial of YL201, tumor types were not restricted. During the trial, we observed notable antitumor activity in NPC patients, prompting the research team to expand the NPC cohort. The results were encouraging: YL201 achieved an objective response rate (ORR) of 48.6% in previously treated NPC patients—a rate significantly higher than that of existing treatment options [5]. These findings were also included in the Nature Medicine publication.

Based on the strong efficacy data, our team rapidly initiated a phase III clinical trial in NPC, directly comparing YL201 to the current standard of care. This trial is now actively ongoing. We believe this effort represents a meaningful contribution from our clinical research team to patients in southern China and regions with similar disease patterns.

It is worth highlighting that although many domestic and international B7-H3-targeted therapies are under development, most of them have focused on small cell lung cancer due to its high B7-H3 expression. YL201 is the first drug globally to demonstrate significant clinical efficacy against nasopharyngeal carcinoma (NPC) via B7-H3 targeting and is also the first B7-H3 ADC worldwide to advance into a phase III trial for the treatment of NPC. These findings represent a meaningful breakthrough and bring new hope for NPC patients.

We sincerely hope that YL201 will become available as a treatment option soon—not only to benefit a broad range of lung cancer patients, but also to offer real clinical value to those with NPC in southern China, where the disease burden is particularly high. This is one of the key innovations of the study.

04 | Oncology Frontier:

As a leading example of a domestically developed anti-cancer drug, YL201 by Elensys Bio has demonstrated both efficacy and safety in clinical studies. It has received Breakthrough Therapy Designation from China’s CDE for relapsed SCLC and Orphan Drug Designation from the U.S. FDA for esophageal cancer. What are your expectations for its future development?

Prof. Hongyun Zhao:At present, phase III clinical trials of YL201 are underway to further evaluate its long-term survival benefits and safety in a broader patient population. We’ve had interest from media outlets and patients alike regarding its performance in other tumor types. As an ADC—often referred to as a “chemotherapy-guided missile” or “magic bullet”—YL201 is not inherently limited to one specific cancer. We believe its future applications are broad and promising.

That said, fully realizing this potential will require more supporting data from phase I studies, as well as confirmation from phase II and III trials. While YL201 has already been granted orphan drug status for esophageal cancer in the U.S., other tumor types—including esophageal cancer—have not yet progressed to phase III, and thus were not the focus of our initial research.

Nonetheless, we see substantial potential for further exploration of YL201 in other cancers, but this will depend on accumulating more clinical evidence. In the future, combination strategies—such as pairing YL201 with immunotherapy, monoclonal antibodies, or bispecific antibodies—may further enhance its efficacy and prolong response duration. These avenues will be key areas of investigation going forward.

Moreover, YL201’s utility may not be limited to the tumor types already mentioned. Should data reveal strong efficacy in other cancers, larger-scale clinical trials will be initiated to validate those findings.

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References:

1. Expert Panel on Standardized Perioperative Immunotherapy for Non-Small Cell Lung Cancer. Expert consensus on standardized perioperative immunotherapy for non-small cell lung cancer. Chinese Journal of Clinical Oncology, 2024, 51(9): 433–446.
2. Chinese Society of Clinical Oncology (CSCO) Small Cell Lung Cancer Expert Committee, Chinese Medical Doctor Association Multidisciplinary Oncology Committee. Expert consensus on immunotherapy for small cell lung cancer (2025 edition). Chinese Journal of Oncology, 2025, 47(1): 65–75.
3. Fox, Wallace, and J.G. Scadding. Medical Research Council comparative trial of surgery and radiotherapy for primary treatment of small-celled or oat-celled carcinoma of bronchus: ten-year follow-up. The Lancet, 1973, 302(7820): 63–65.
4. Toh, T.S., and Lok, B.H. Limited-Stage Small-Cell Lung Cancer: Current Progress and the Next Frontier. Radiation, 2021, 1(4): 317–333.
5. Ma, Yuxiang, et al. A B7H3-targeting antibody–drug conjugate in advanced solid tumors: a phase 1/1b trial. Nature Medicine, 2025: 1–9.

Chief Physician, Doctoral Supervisor, Deputy Chief Professor Director of the Department of Thoracic Oncology, Sun Yat-sen University Cancer Center Leading Expert in Lung Cancer

• Chair, Committee on Cancer Rehabilitation and Symptom Management, Chinese Anti-Cancer Association (CACA)
• Chair-designate, Committee on Clinical Research of Anti-Tumor Drugs, CACA
• Chair, Expert Panel on Immunotherapy, Chinese Society of Clinical Oncology (CSCO)
• Chair, Committee on Non-Small Cell Lung Cancer, CSCO
• Deputy Chair, Expert Panel on Lung Cancer Rehabilitation and Symptom Management, CSCO
• Chair, Clinical Oncology Branch, Guangdong Medical Association
• Member, Precision Medicine Committee, Guangdong Medical Association

Chief Physician, Doctoral Supervisor, Professor Director of the Early-Phase Clinical Trials Ward and Deputy Director of the Department of Clinical Research, Sun Yat-sen University Cancer Center

• Chair, Committee on Precision Therapy for Lung Cancer, Guangdong Medical Association
• Deputy Chair, Committee on Clinical Research of Anti-Tumor Drugs, CACA
• Deputy Chair, Youth Committee of the Chemotherapy Expert Committee, Guangdong Anti-Cancer Association
• Expert Advisor, “Healthy China 2030” National Project on Individualized Treatment Strategies for Lung Cancer