Positive Results from Phase 3 OptiTROP-Lung04 Trial of Sacituzumab Tirumotecan Presented at ESMO Presidential Symposium and Simultaneously Published in NEJM
CHENGDU, China , Oct. 19, 2025 /PRNewswire/ -- Sichuan Kelun-Biotech Biopharmaceutical Co., Ltd. (the "Company") announced that at the 2025 European Society for Medical Oncology (ESMO) Congress held in Berlin, Germany, results from a Phase 3 OptiTROP-Lung04 trial of the Company's trophoblast cell-surface antigen 2 (TROP2)-directed antibody-drug conjugate (ADC) sacituzumab tirumotecan (sac-TMT) in EGFR-mutated non-small cell lung cancer (NSCLC) following progression on epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) was presented as an oral report by Professor Li Zhang from Sun Yat-sen University Cancer Center (Presentation # LBA5, Presidential Symposium II) and were simultaneously published in the New England Journal of Medicine (Impact Factor = 78.5).
In the OptiTROP-Lung04 trial, a total of 376 patients were randomized (1:1) to receive sac-TMT monotherapy or chemotherapy.
As at the data cut-off date July 06, 2025, the median follow-up is 18.9 months. the median Progression-Free Survival (PFS) was 8.3 months in the sac-TMT group and 4.3 months in the chemotherapy group. Sac-TMT significantly improved PFS over chemotherapy with 51% lower risk of disease progression or death (hazard ratio (HR) 0.49; 95% confidence interval (CI), 0.39-0.62; P<0.0001).
At the preplanned interim analysis of overall survival (OS), the OS was not reached (NR) in the sac-TMT group and 17.4 months in the chemotherapy group. sac-TMT significantly improved OS over chemotherapy with 40% lower risk of death (hazard ratio (HR) 0.6; 95% CI: 0.44-0.82; two-sided P=0.001). In the supplemental analysis, when censoring patients at the date of initiation of subsequent ADCs, sac-TMT significantly improved OS over chemotherapy with 44% lower risk of death (HR, 0.56; 95% CI, 0.41 - 0.77).
Sac-TMT significantly improved ORR as compared to chemotherapy (60.6% vs 43.1%)
A consistent PFS and OS benefit of sac-TMT over chemotherapy was observed across all predefined subgroups, including prior EGFR-TKI therapy, presence of liver or brain metastases, and EGFR mutation subtype.
The incidence of any grade treatment-related adverse events (TRAEs) and grade ≥3 TRAEs was similar between the two groups. The most common TRAEs for both sac-TMT and chemotherapy were hematologic toxicities. No TRAEs led to discontinuation or death, and no cases of interstitial lung disease/pneumonitis were reported in the sac-TMT group. Ocular surface toxicity: occurred in 9.6% of patients in the sac-TMT group, all of which were grade 1 - 2.
As a conclusion, sac-TMT demonstrates highly statistically significant and clinically meaningful improvements in PFS and OS compared to platinum-based chemotherapy and showed a manageable safety profile, with no unexpected safety signals identified. Several global phase 3 studies of sac-TMT monotherapy (NCT06305754, NCT06074588) and combination study with osimertinib in China (NCT06670196) in EGFR-mutant NSCLC are ongoing.
Professor Zhang Li, National Lead Principal Investigator from Sun Yat-sen University Cancer Center, commented: "Compared to platinum-based doublet chemotherapy, sac-TMT not only significantly prolonged PFS but also demonstrated a statistically significant and clinically meaningful improvement in OS within this patient population. This achievement marks a major breakthrough in global lung cancer treatment—sac-TMT, as a monotherapy, demonstrated statistically significant and clinically meaningful improvements in both PFS and OS in the Phase III trial for patients with EGFR-TKI-resistant NSCLC. This study provides highly valuable, new evidence-based guidance for lung cancer management worldwide and has the potential to reshape the therapeutic landscape for EGFR-TKI-resistant NSCLC "
About sac-TMT
Sac-TMT, a core product of the Company, is a novel human TROP2 ADC in which the Company has proprietary intellectual property rights, targeting advanced solid tumors such as NSCLC, BC, GC, gynecological tumors, among others. Sac-TMT is developed with a novel linker to conjugate the payload, a belotecan-derivative topoisomerase I inhibitor with a drug-to-antibody-ratio (DAR) of 7.4. Sac-TMT specifically recognizes TROP2 on the surface of tumor cells by recombinant anti-TROP2 humanized monoclonal antibodies, which is then endocytosed by tumor cells and releases the payload KL610023 intracellularly. KL610023, as a topoisomerase I inhibitor, induces DNA damage to tumor cells, which in turn leads to cell-cycle arrest and apoptosis. In addition, it also releases KL610023 in the tumor microenvironment. Given that KL610023 is membrane permeable, it can enable a bystander effect, or in other words kill adjacent tumor cells.
In May 2022, the Company licensed the exclusive rights to MSD (the tradename of Merck & Co., Inc, Rahway, NJ, USA) to develop, use, manufacture and commercialize sac-TMT in all territories outside of Greater China (which includes Mainland China, Hong Kong, Macao and Taiwan).
To date, three indications for sac-TMT have been approved and marketed in China for the treatment of adult patients with unresectable locally advanced or metastatic triple negative breast cancer (TNBC) who have received at least two prior systemic therapies (at least one of them for advanced or metastatic setting), EGFR mutation-positive locally advanced or metastatic non-squamous NSCLC following progression on EGFR-TKI therapy and platinum-based chemotherapy and EGFR mutant-positive locally advanced or metastatic non-squamous NSCLC who progressed after treatment with EGFR-TKI therapy. Sac-TMT is the first TROP2 ADC drug approved for marketing in lung cancer globally. In addition, the new indication applications for sac-TMT for the treatment of adult patients with unresectable locally advanced, metastatic HR+/HER2- BC who have received prior endocrine therapy and other systemic treatments in the advanced or metastatic setting was accepted by the Center for Drug Evaluation (CDE) of the National Medical Products Administration (NMPA), and was included in the priority review and approval process.
As of today, the Company has initiated 9 registrational clinical studies in China. MSD has initiated 15 ongoing Phase 3 global clinical studies of sac-TMT as a monotherapy or with pembrolizumab or other anti-cancer agents for several types of cancer. These studies are sponsored and led by MSD.
About Kelun-Biotech
Kelun-Biotech (6990.HK) is a holding subsidiary of Kelun Pharmaceutical (002422.SZ), which focuses on the R&D, manufacturing, commercialization and global collaboration of innovative biological drugs and small molecule drugs. The company focuses on major disease areas such as solid tumors, autoimmune, inflammatory, and metabolic diseases, and in establishing a globalized drug development and industrialization platform to address the unmet medical needs in China and the rest of world. The Company is committed to becoming a leading global enterprise in the field of innovative drugs. At present, the Company has more than 30 ongoing key innovative drug projects, of which 4 projects have been approved for marketing, 1 project is in the NDA stage and more than 10 projects are in the clinical stage. The company has established one of the world's leading proprietary ADC and novel DC platforms, OptiDC™, and has 2 ADC project approved for marketing and multiple ADC and novel DC assets in clinical or preclinical research stage. For more information, please visit https://kelun-biotech.com/.
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