On June 6, 2025 Sichuan Kelun-Biotech Biopharmaceutical Co., Ltd. ("Kelun-Biotech", 6990.HK) reported that results from its registrational study (OptiTROP-Lung03) evaluating sacituzumab tirumotecan (sac-TMT) versus docetaxel in patients with previously treated advanced EGFR-mutant non-small cell lung cancer (NSCLC) have been published in The British Medical Journal (impact factor: 93.6) (Press release, Kelun, JUN 6, 2025, View Source [SID1234653767]). These data were also presented as an oral presentation in the Lung Cancer—Non–Small Cell Metastatic session (Abstract #8507) at the 2025 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting. Based on the encouraging data from this study, sac-TMT was approved for marketing by the National Medical Products Administration (NMPA) for the treatment of adult patients with epidermal growth factor receptor (EGFR) mutant-positive locally advanced or metastatic non-squamous NSCLC following progression on EGFR-tyrosine kinase inhibitor (TKI) therapy and platinum-based chemotherapy in March 2025. This marks the first global approval of a TROP2 ADC for a lung cancer indication.
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The published results are based on OptiTROP-Lung03, an open-label, randomized, multicenter registrational study evaluating the efficacy and safety profile of sac-TMT monotherapy versus docetaxel for the treatment of patients with locally advanced or metastatic EGFR-mutant NSCLC who have failed after treatment with an EGFR-TKI and platinum-based chemotherapy. A total of 137 patients with advanced EGFR-mutant NSCLC who had progressed after EGFR-TKI and platinum-based chemotherapy were randomized (2:1) to receive sac-TMT (5 mg/kg once every 2 weeks) or docetaxel (75 mg/m2 once every 3 weeks) until disease progression, intolerable toxicity or other reason for discontinuation, with a median follow-up time of 12.2 months (Data cutoff date: December 31, 2024).
Sac-TMT achieved statistically significant and clinically meaningful outcomes compared to docetaxel:
Confirmed objective response rate (ORR) (As assessed by blinded independent review committee (BIRC): 45% (95% CI, 35-56) vs 16% (95% CI, 7-30).
Median progression-free survival (PFS) (As assessed by BIRC: 6.9 months [sac-TMT; 95% CI, 5.4-8.2] vs 2.8 months [docetaxel; 95% CI, 1.6-4.1], hazard ratio (HR)= 0.30 [range, 0.20 -0.46], one-sided p<0.0001; as assessed by investigator (INV): 7.9 months [sac-TMT; 95% CI, 6.2-9.5] vs 2.8 months [docetaxel; 95% CI, 1.5-3.8], HR=0.23 [95% CI, 0.15-0.36], one-sided p<0.0001).
With 36.4% of patients in docetaxel group crossing over to receive sac-TMT, median overall survival (OS) was not reached (NR) for both groups (HR=0.49; 95% CI, 0.27-0.88; one-sided p=0.007). The median OS analysed by pre-specified rank-preserving structural failure time (RPSFT) model adjusted for crossover was 9.3 months for docetaxel and NR for sac-TMT (HR=0.36; 95% CI, 0.20-0.66).
Efficacy benefit favored patients with sac-TMT over docetaxel across all pre-specified subgroups, including prior EGFR-TKI therapy, brain metastases, EGFR mutation type, etc.
Grade ≥ 3 treatment-related adverse events (TRAEs) occurred in 56.0% of patients in sac-TMT group vs 71.7% in docetaxel group.
The results demonstrated that sac-TMT monotherapy achieved statistically significant and clinically meaningful improvements in objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) compared to docetaxel, with a manageable safety profile.
Sac-TMT is being extensively studied in the NSCLC field. Covering treatment settings from later-line therapy to early-stage postoperative adjuvant therapy, including both monotherapy and combination regimens. Currently, five company-led registrational clinical studies for sac-TMT in NSCLC are underway in China. Meanwhile, Merck Sharp & Dohme（the tradename of Merck & Co., Inc., Rahway, NJ, USA）is also conducting five global Phase III clinical trials of sac-TMT for NSCLC in regions where it has exclusive rights.
Professor Li Zhang, National Lead Principal Investigator, Medical Oncologist and Deputy Director of the Lung Cancer Research Centre at Sun Yat-Sen University, stated: "EGFR mutation is the most common driver alteration in NSCLC. The prevalence of EGFR mutations reaches 28.2% among NSCLC patients in China. Although third-generation EGFR-TKIs have become the standard of care for advanced EGFR-mutant NSCLC and may significantly improve PFS, acquired resistance remains inevitable. Combining EGFR-TKIs with chemotherapy can offer additional survival benefits to some patients, but this approach is limited by safety concerns and may compromise future treatment options, posing significant clinical challenges. The publication of the OptiTROP-Lung03 study in the British Medical Journal marks a major milestone—not only highlighting international recognition of this study outcomes in lung cancer, but also demonstrating the global competitiveness of sac-TMT as a novel TROP2 ADC."
Dr. Michael Ge, CEO of Kelun-Biotech, commented: "We are thrilled to see the OptiTROP-Lung03 study published in a top-tier journal. Currently, EGFR-TKIs and chemotherapy remain the standard of care for patients with EGFR-mutant advanced NSCLC, but the challenge of increasing efficacy with manageable tolerability. The results from OptiTROP-Lung03 highlight significant survival benefits with manageable safety profile and suggest that sac-TMT could emerge as a new standard of care for this population. We remain committed to working with our partners to establish sac-TMT as a new standard of care for this patient population and improve outcomes for lung cancer patients worldwide."
Registrational Study Led by Kelun-Biotech
OptiTROP-Lung03: Sac-TMT monotherapy versus docetaxel for locally advanced or metastatic EGFR-mutant NSCLC after treatment failure with EGFR-TKI and platinum-containing chemotherapy；
OptiTROP-Lung04: Sac-TMT monotherapy versus pemetrexed in combination with platinum for locally advanced or metastatic non-squamous NSCLC with EGFR mutations that have failed EGFR-TKI therapy；
OptiTROP-Lung05: Sac-TMT combined with pembrolizumab versus chemotherapy combined with pembrolizumab for first-line treatment of PD-L1-positive locally advanced or metastatic NSCLC;
OptiTROP-Lung06: Sac-TMT combined with pembrolizumab versus chemotherapy combined with pembrolizumab for the first-line treatment of PD-L1-negative locally advanced or metastatic non-squamous NSCLC;
OptiTROP-Lung07: First-line treatment of locally advanced or metastatic NSCLC with EGFR mutations by sac-TMT in combination with ositinib.
Registrational Study Led by MSD
NSCLC not achieving a pCR after neoadjuvant therapy followed by surgery.
NSCLC expressing PD-L1 >50%
pre-treated NSCLC with EGFR mutations or other genomic alterations
EGFR-mutated, advanced non-squ NSCLC progressed on prior EGFR-TK
metastatic sg 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, gastric cancer (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 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 (includes Mainland China, Hong Kong, Macao, and Taiwan).
To date, two indications for sac-TMT have been approved and marketed in China for the treatment of adult patients with unresectable locally advanced or metastatic TNBC who have received at least two prior systemic therapies (at least one of them for advanced or metastatic setting) based on the OptiTROP-Breast01 study and EGFR mutation-positive locally advanced or metastatic non-squamous NSCLC following progression on EGFR-TKI therapy and platinum-based chemotherapy based on the OptiTROP-Lung03 study. Sac-TMT became the first domestic ADC with global intellectual property rights to be fully approved for marketing. It is also the world’s first TROP2 ADC to be approved for marketing in a lung cancer indication. In addition, two new indication applications for sac-TMT for the treatment of adult patients with EGFR-mutant locally advanced or metastatic NSCLC who progressed after treatment with EGFR-TKI therapy and with unresectable locally advanced, metastatic hormone receptor-positive (HR+) and human epidermal growth factor receptor 2-negative (HER2-) BC who have received prior endocrine therapy and other systemic treatments in the advanced or metastatic setting were accepted by the National Medical Products Administration (NMPA), and were reviewed via the priority review and approval process. As of today, the Company has initiated 8 registrational clinical studies in China. MSD has initiated 14 ongoing Phase 3 global clinical studies of sac-TMT as a monotherapy or with pembrolizumab or other agents for several types of cancer. These studies are sponsored and led by MSD.