Significant Advancements in Lung Cancer Treatment with Sacituzumab Tirumotecan from Recent Clinical Trials

Breakthrough in Lung Cancer Treatment: The OptiTROP-Lung04 Trial Results

Introduction

Sichuan Kelun-Biotech Biopharmaceutical Co., Ltd. recently unveiled key data from its Phase 3 OptiTROP-Lung04 trial at the European Society for Medical Oncology (ESMO) Congress held in Berlin. The trial focused on sacituzumab tirumotecan (sac-TMT), a novel antibody-drug conjugate targeting the TROP2 protein, in patients with EGFR-mutated non-small cell lung cancer (NSCLC) who had shown disease progression following treatment with EGFR-TKIs (tyrosine kinase inhibitors).

Trial Overview

The OptiTROP-Lung04 trial involved 376 patients randomized to receive either sac-TMT monotherapy or traditional chemotherapy. Data from July 6, 2025, indicated that patients receiving sac-TMT experienced a median progression-free survival (PFS) of 8.3 months, significantly exceeding the 4.3 months observed in those receiving chemotherapy. These findings suggest a 51% reduction in the risk of disease progression or death (hazard ratio [HR] 0.49; p<0.0001).

At the preplanned interim analysis for overall survival (OS), data revealed that the sac-TMT group achieved significantly better outcomes compared to the chemotherapy group, with a notable 40% reduction in the risk of death (HR 0.6; P=0.001). This is noteworthy given that the median OS for the chemotherapy group was only 17.4 months at that point. Furthermore, when censoring patients at the initiation of subsequent ADCs, sac-TMT showed a 44% lower risk of mortality (HR, 0.56).

Other Promising Results

Additionally, sac-TMT demonstrated an objective response rate (ORR) of 60.6%, compared to 43.1% in the chemotherapy cohort. These results were consistent across various patient subgroups, including those with prior EGFR-TKI therapy and metastatic disease in the liver or brain.

Adverse events were comparable between the two treatment regimens, with no unexpected safety signals emerging. Hematologic toxicities were reported as the most common treatment-related adverse events (TRAEs) for both groups. It's worth noting that no cases of interstitial lung disease or pneumonitis were reported within the sac-TMT group. However, ocular surface toxicity was experienced by 9.6% of sac-TMT patients, primarily classified as grade 1-2.

Conclusion

These positive trial results for sac-TMT mark a significant milestone in the treatment landscape for patients with EGFR-TKI-resistant NSCLC. Professor Li Zhang from the Sun Yat-sen University Cancer Center stated that this treatment represents an important evolution in lung cancer management, showcasing not only improved PFS but also significant OS enhancements compared to standard chemotherapy options.

About Sac-TMT and Future Directions

Sacituzumab tirumotecan is recognized for its targeted approach against advanced solid tumors, including NSCLC. Its unique mechanism involves a proprietary linker that joins the chemotherapy agent, belotecan, to the TROP2-targeted antibody, facilitating selective targeting of cancer cells. The promising results from the OptiTROP-Lung04 trial have paved the way for ongoing and future phase 3 studies, including its combination with other agents.

Given the advancements noted in the trial, sac-TMT has the potential not only to reshape treatment strategies for lung cancer but also to offer new hope to patients struggling with aggressive cancer types. As further data and studies are compiled from ongoing clinical trials, the future appears promising for patients benefitting from this innovative therapeutic approach.