Kelun-Biotech's Sac-TMT: Redefining Targeted Therapy in EGFRm NSCLC Post-TKI Failure

The approval of Kelun-Biotech's TROP2 antibody-drug conjugate (ADC), sacituzumab tirumotecan (Sac-TMT), by China's National Medical Products Administration (NMPA) in October 2025 marks a pivotal moment in the treatment of epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC). This third indication for Sac-TMT-specifically for patients who have progressed after EGFR-tyrosine kinase inhibitor (TKI) therapy-positions the drug as a groundbreaking therapeutic option in a high-unmet-need setting. With its demonstrated ability to deliver statistically significant and clinically meaningful improvements in both progression-free survival (PFS) and overall survival (OS) compared to platinum doublet chemotherapy, Sac-TMT is redefining the standards of care for EGFRm NSCLC and solidifying its strategic value in the evolving oncology landscape, according to a PR Newswire release.

A New Benchmark in Post-TKI Therapy

The OptiTROP-Lung04 trial, which underpinned the October 2025 NMPA approval, demonstrated that Sac-TMT outperformed pemetrexed plus platinum chemotherapy in both PFS and OS metrics. This achievement is particularly notable given the historical challenges of improving OS in EGFRm NSCLC post-TKI failure. Prior to Sac-TMT, no ADC had demonstrated a survival advantage in this patient population, despite the urgent need for alternatives to conventional chemotherapy, which is associated with significant toxicity and limited efficacy; the PR Newswire release highlighted these points.

The March 2025 approval of Sac-TMT for EGFRm NSCLC patients who had progressed after EGFR-TKI and platinum-based chemotherapy further underscored its potential, as reported in a BioSpace report. The OptiTROP-Lung03 trial showed a 40% improvement in PFS and a 25% reduction in mortality risk compared to docetaxel, a standard second-line therapy. Now, with the third indication, Sac-TMT's label has expanded to cover a broader spectrum of TKI-treated patients, including those who may not have received prior platinum-based chemotherapy. This broad coverage enhances its market accessibility and therapeutic relevance, as the BioSpace report noted.

Strategic Differentiation in a Competitive Landscape

The EGFRm NSCLC treatment landscape post-TKI failure remains fragmented, with current standards of care including combinations of third-generation EGFR TKIs (e.g., osimertinib) with anti-angiogenic agents, chemotherapy, or the EGFR–MET bispecific antibody amivantamab. However, these approaches often fail to address the root mechanisms of resistance, such as MET amplification, EGFR C797S mutations, or drug-tolerant persister cells, according to a Nature review.

Sac-TMT's mechanism of action-targeting TROP2, a cell surface antigen overexpressed in various cancers, including NSCLC-offers a distinct advantage. By delivering a cytotoxic payload directly to tumor cells, Sac-TMT circumvents intracellular resistance pathways that limit the efficacy of TKIs. This extracellular targeting strategy not only enhances tumor cell kill but also minimizes systemic toxicity, a critical factor in long-term patient management, as described in the PR Newswire release.

Competitive ADCs in development, such as amivantamab (approved for MET-driven NSCLC) and telisotuzumab vedotin (Teliso-V), have shown modest response rates in trials but lack the OS benefits demonstrated by Sac-TMT. For instance, the CHRYALSIS trial reported a 36% overall response rate (ORR) for amivantamab combined with lazertinib in post-osimertinib patients, but no OS data was provided, an observation highlighted in the BioSpace coverage. In contrast, Sac-TMT's OS advantage positions it as a superior option for patients with limited therapeutic alternatives.

Market Potential and Future Directions

China's NSCLC market is a critical growth driver for Sac-TMT. With approximately 1.06 million new lung cancer cases diagnosed annually and NSCLC accounting for the majority of these, the demand for innovative therapies is immense, the PR Newswire release emphasized. Sac-TMT's approvals align with the NMPA's recent focus on accelerating access to biomarker-driven treatments, a trend that bodes well for its adoption.

Looking ahead, Sac-TMT's development in combination with osimertinib for first-line treatment of EGFRm NSCLC represents a high-impact opportunity. The Phase III registrational study in China has already completed patient enrollment, suggesting a potential expansion into earlier lines of therapy. If successful, this strategy could position Sac-TMT as a cornerstone of EGFRm NSCLC management, bridging the gap between first-line TKIs and post-progression therapies, as noted in the PR Newswire release.

Conclusion

Kelun-Biotech's Sac-TMT has emerged as a transformative ADC in the EGFRm NSCLC space, leveraging its OS benefits, broad patient coverage, and differentiated mechanism to address critical unmet needs. With three NMPA approvals and an ongoing first-line trial, the drug's strategic value is underscored by its ability to redefine treatment paradigms in a market where resistance to TKIs remains a persistent challenge. As the ADC class continues to evolve, Sac-TMT's clinical and commercial trajectory offers a compelling case for investors seeking exposure to innovation-driven oncology therapies.