The 2025 ESMO Congress was held in Berlin, Germany, from October 17 to 21 (local time), bringing together cutting-edge concepts and latest breakthroughs in international oncology research. Legubicin, a tumor microenvironment-activated small-molecule/albumin conjugate independently developed by Affinity , has had its first Phase III registration study results selected as a Late-Breaking Abstract (LBA) at the 2025 European Society for Medical Oncology (ESMO) Congress. The first-time data were presented in an oral session during the Proffered Paper Session: Sarcoma on October 19 (local time). This registration trial is a first-line, randomized, double-blind, head-to-head study comparing legubicin with doxorubicin for soft tissue sarcoma (STS). Clinical development of legubicin is ongoing or being initiated across multiple tumor types.

Details of the Oral Presentation

· Abstract Number: LBA97

· Study Title: Legubicin versus doxorubicin (DOX) in patients (pts) with advanced soft tissue sarcoma (STS): results of a randomized Phase II/III study

· Presenter: Professor Shen Zan (Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University)

· Session: Proffered Paper Session: Sarcoma

· Local Time: 16:30–16:40, October 19, 2025 (Beijing Time: 22:30–22:40, October 19)

· Venue: Dortmund Auditorium – Hall 7.1a

Presentation Summary

Professor Shen Zan, Director of Medical Oncology at Shanghai Sixth People’s Hospital, Shanghai Jiao Tong University School of Medicine, and Principal Investigator of the QHL-Legubicin-102 study, delivered the oral presentation and shared this key achievement with the global oncology community. This marks the highest-level evidence in China’s advanced soft tissue sarcoma field being recognized by an authoritative international academic conference.

The trial enrolled 306 patients with advanced soft tissue sarcoma (STS). The primary endpoint, progression-free survival (PFS), was significantly superior with legubicin versus doxorubicin. Median PFS (mPFS) assessed by the blinded independent review committee (IRC) was 10.4 months vs. 4.9 months (HR = 0.50; 95% CI: 0.35–0.70; P < 0.0001).Legubicin also demonstrated a significant overall survival (OS) benefit: the 25th percentile of OS (OS P25) was 23.6 months vs. 13.8 months (HR = 0.49; 95% CI: 0.30–0.79), representing an improvement of more than 70%.Additionally, legubicin achieved higher objective response rate (ORR) and disease control rate (DCR) compared with doxorubicin.

The primary dose-limiting toxicity associated with doxorubicin is cardiotoxicity. Legubicin reduced the incidence of grade ≥3 cardiotoxicity by more than 20-fold (1.9% in the legubicin group vs. 39.7% in the doxorubicin group). The incidence of other common grade ≥3 treatment-related adverse events (TRAEs) was also significantly reduced, including hematologic-related events (30.6% vs. 92.5%), gastrointestinal-related events (0% vs. 3.4%), and treatment-related alopecia (13.8% vs. 74.0%). These results demonstrate statistically significant differences and substantial clinical benefits, bringing new hope to patients with soft tissue sarcoma.

About soft tissue sarcoma (STS)

Currently, patients with advanced soft tissue sarcoma have poor survival outcomes. The median overall survival (OS) of patients with advanced STS is approximately 14 months [1], and the 5-year survival rate for patients with stage IV disease according to the AJCC staging system is only 13.9% [2]. According to the latest statistics from the U.S. National Cancer Institute’s SEER database, there has been no significant improvement in the 5-year survival rate over the past three decades, and the poor prognosis in advanced patients is largely attributed to the lack of low-toxicity, highefficacy maintenance therapies [3].

Palliative chemotherapy is based on doxorubicin (DOX). Firstline chemotherapy is primarily doxorubicin-based, but it is associated with dose-limiting toxicities (acute hematologic toxicity and cardiotoxicity). In particular, the cumulative, dose-limiting cardiotoxicity restricts doxorubicin use, with a recommended cumulative dose of ≤550 mg/m² [4]. There is no universally accepted second-line chemotherapy regimen, and treatment is selected based on pathological subtype. There is also a lack of long-term maintenance treatment options for soft tissue sarcoma.

This study supports that legubicin is a promising and safe therapeutic option for soft tissue sarcoma with the potential for long-term maintenance treatment. It demonstrates that legubicin may replace doxorubicin (DOX) and provides clinical evidence for the tumor microenvironment-activated (TMEA) XDC platform drugs, including legubicin. By overcoming the dose-limitations of anthracyclines, legubicin is expected to reshape chemotherapy and combination treatment paradigms, enabling broader clinical application and benefiting more patients.

References：

1. 《评价软组织肉瘤患者多柔比星治疗的疗效和安全性：基于临床试验的汇总分析》;

2. Comparative performance of the 7th and the 8th editions of the American Joint Committee on Cancer staging systems for soft tissue sarcoma of the trunk and extremities;

3. SEER: Soft Tissue Cancer — Cancer Stat Facts;

4. Pfizer. Prescribing Information for Doxorubicin Hydrochloride for Injection;

About Affinity (Shanghai) Biopharmaceutical Co., Ltd. ("Affinity")

Affinity is an innovative biopharmaceutical company dedicated to the research, development, production, commercialization and global collaboration of first-in-class and best-in-class novel anti-cancer drugs. We have built a globally original and proprietary technology platform for multi-specific intelligent conjugates activated exclusively within the tumor microenvironment.

Our integrated R&D system consists of two major branches:TMEA-XDC (Tumor Microenvironment-Activated Multi-specific Conjugates), covering ALDC, SMDC and ADC;TMEA-IO (Tumor Microenvironment-Activated Immunotherapeutics), including monoclonal antibodies, bispecific antibodies, TCEs and cytokines.The Company has developed more than 20 novel candidate drugs for the treatment of cancer and other major diseases.

The pivotal first-line, double-blind, head-to-head clinical trial comparing our independently developed tumor microenvironment-activated small-molecule conjugate Legubicin versus doxorubicin for soft tissue sarcoma has been unblinded. The legubicin arm showed a substantially expanded therapeutic window and an excellent safety profile. The drug largely addresses the cardiotoxicity associated with anthracyclines and delivers a significant prolongation of progression-free survival.

Affinity actively advances collaborative development. We have out-licensed the domestic rights of two high-potential pipeline assets and expect steady revenue therefrom. Meanwhile, multiple novel drugs are being developed via our technology licensing partnerships. Leveraging our proprietary platforms, the Company aims to develop first-in-class and best-in-class new drugs as well as combination regimens, strive to become a leading player in the field, and ultimately benefit cancer patients worldwide.

Shanghai Affinity Biopharmaceutical Co., Ltd. is a subsidiary of  Affinity (Shanghai) Biopharmaceutical Co., Ltd. (referred to as “Affinity” or “the Company”).