Sacituzumab tirumotecan (佳泰莱®/Jiataile®, sac-TMT, formerly SKB264/MK-2870; Sichuan Kelun-Biotech Biopharmaceutical), a trophoblast cell-surface antigen 2 (TROP2)-directed antibody-drug conjugate (ADC), was approved for marketing by the Chineses National Medical Products Administration (NMPA) for the second indication which is for the treatment of adult patients with epidermal growth factor receptor (EGFR) mutant-positive locally advanced or metastatic non-squamous non-small cell lung cancer (NSCLC) following progression on EGFR-tyrosine kinase inhibitor (TKI) therapy and platinum-based chemotherapy.
Lung cancer
Lung cancer, the second most common cancer in the world, includes two main types of cancer: non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC). NSCLC is the most common pathological type, accounting for about 80 to 85% of all lung cancers. The molecular typing of NSCLC patients in China is different from that of Western populations, and EGFR mutation is a common variant gene type, accounting for about 40 to 50% of lung adenocarcinoma patients in China.
According to the 2024 Chinese Journal of Cancer Research (CSCO) guidelines, EGFR-TKIs are the preferred treatment for stage IV EGFR-mutant NSCLC. [1] Platinum-containing chemotherapy is the main first-line chemotherapy regimen after resistance to EGFR-TKIs; and existing treatment regimens are ineffective in those who have failed EGFR-TKIs and platinum-containing chemotherapy. New drugs are urgently needed to improve patient survival.
Sacituzumab tirumotecan is the first TROP2 ADC drug approved for marketing in lung cancer globally. Compared with current standard of care, sacituzumab tirumotecan significantly extents the overall survival benefits of these patients.
Sacituzumab tirumotecan 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. sacituzumab tirumotecan 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.
First approval: Breast cancer
A analysis of China’s malignant tumor epidemiology data shows that there are 357,000 new cases of breast cancer and 75,000 deaths in Chinese women annually.[2] In the absence of effective therapeutic targets for triple-negative breast cancer, chemotherapy is the most important systemic treatment in the clinic. [3]
In November 2024 sacituzumab tirumotecan received its first marketing authorization in China from the National Medical Products Administration (NMPA) 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 which is for advanced or metastatic stage), based on results from the Phase 3 OptiTROP-Breast01 study.
This approval was based on a multi-center, randomized, controlled, pivotal study (OptiTROP-Lung03) that evaluates the efficacy and safety profile of sacituzumab tirumotecan monotherapy 5mg/kg every other week (Q2W) as an intravenous injection 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 (used sequentially or in combination).
As demonstrated in a pre-specified interim analysis, sacituzumab tirumotecan monotherapy demonstrated a statistically significant and clinically meaningful improvement in objective response rate (ORR), progression-free survival (PFS) and overall survival (OS) compared with docetaxel.
Sacituzumab tirumotecan is also the first ADC drug to demonstrate a statistically and clinically significant improvement in overall survival benefit versus standard of care in patients with EGFR-mutant NSCLC after failure of EGFR-TKI and platinum-based chemotherapy.
Ongoing trials
Currently, Merck & Co/MSD* and Sichuan Kelun-Biotech Biopharmaceutical are conducting a total of 10 registrational Phase 3 clinical studies in NSCLC globally and in China, with the threads covering from the late backline to early postoperative adjuvant, including monotherapy and combination studies. Among them, a registrational Phase 3 clinical study has been conducted in China in combination with osimertinib (Tagrisso®; AstraZeneca) for the first-line treatment of locally advanced or metastatic NSCLC with EGFR mutations (OptiTROP-Lung07).
“We are very pleased that the second indication of the Company’s TROP2 ADC sacituzumab tirumotecan has been approved for marketing, which is exciting progress for us in the field of lung cancer,” noted Michael Ge, CEO of Kelun-Biotech
“The successful approval of this new indication will help to address an unmet treatment need for patients with later-stage EGFRm NSCLC in China. Kelun-Biotech has always been committed to promoting innovation and leadership, and we look forward to continuing our research in the field of ADCs in partnership with MSD,” Ge concluded.
FDA Breakthrough designation
In early December 2024 the U.S. Food and Drug Administration (FDA) granted Breakthrough Therapy designation to sacituzumab tirumotecan for the treatment of patients with advanced or metastatic nonsquamous non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutations (exon 19 deletion [19del] or exon 21 L858R) whose disease progressed on or after tyrosine kinase inhibitor (TKI) and platinum-based chemotherapy.
Genitourinary Cancer
At the American Society of Clinical Oncology (ASCO) Genitourinary (GU) Cancers Symposium, held in San Francisco, USA, from February 13-15, 2025, efficacy and safety results from the Phase 1/2 KL264-01/MK-2870-001 study (NCT04152499) were presented.
The outcome of the study showed that sacituzumab tirumotecan monotherapy had promising anti-tumor activity in patients with unresectable, locally advanced urothelial carcinoma who progressed on ≥1 prior line of platinum-based therapy.
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Note:* Merck & Co, is known as known as Merck Sharp & Dohme (MSD) outside of the United States and Canada.
Clinical trials
A Study of Sacituzumab Tirumotecan (Sac-TMT, MK-2870) as Monotherapy and in Combination With Pembrolizumab (MK-3475) in Participants With Triple-Negative Breast Cancer (MK-2870-011/TroFuse-011) – ClinicalTrials.gov ID NCT06841354
A Study to Evaluate the Efficacy and Safety of Sacituzumab Tirumotecan (MK-2870) Treatment Versus Standard of Care in Participants With Platinum-sensitive Recurrent Ovarian Cancer (MK-2870-022/TroFuse-022/ENGOT-ov84/GOG-3103) – ClinicalTrials.gov ID NCT06824467
Pembrolizumab (MK-3475) Plus Investigational Agents in Resectable Non-small Cell Lung Cancer (NSCLC) (MK-3475-01E/KEYMAKER-U01) -ClinicalTrials.gov ID NCT06788912
A Study of Sacituzumab Tirumotecan (MK-2870) as a Single Agent and in Combination With Pembrolizumab (MK-3475) Versus Treatment of Physician’s Choice in Participants With HR+/HER2- Unresectable Locally Advanced or Metastatic Breast Cancer (MK-2870-010) – ClinicalTrials.gov ID NCT06312176
Pembrolizumab With or Without Maintenance Sacituzumab Tirumotecan (Sac-TMT; MK-2870) in Metastatic Squamous Non-small Cell Lung Cancer (NSCLC) [MK-2870-023]
ClinicalTrials.gov ID NCT06422143
A Study to Evaluate Sacituzumab Tirumotecan (MK-2870) in Advanced/Metastatic Gastroesophageal Adenocarcinoma (MK-2870-015) (TroFuse-015) – ClinicalTrials.gov ID NCT06356311
Sacituzumab Tirumotecan (MK-2870) Plus Pembrolizumab Versus TPC in TNBC Who Did Not Achieve pCR (MK-2870-012) – ClinicalTrials.gov ID NCT06393374
A Study of Efficacy and Safety of Sacituzumab Tirumotecan (MK-2870) Plus Enfortumab Vedotin (EV) With and Without Pembrolizumab in Advanced Urothelial Carcinoma (MK-3475-04C/KEYMAKER-U04) – ClinicalTrials.gov ID NCT06483334
A Study of Sacituzumab Tirumotecan (Sac-TMT, MK-2870) as Monotherapy and in Combination With Pembrolizumab (MK-3475) in Participants With Triple-Negative Breast Cancer (MK-2870-011/TroFuse-011) – ClinicalTrials.gov ID NCT06841354
Sacituzumab Tirumotecan (MK-2870) in Combination With Pembrolizumab Versus Pembrolizumab Alone in Metastatic Non-small Cell Lung Cancer (NSCLC) With Programmed Cell Death Ligand 1 (PD-L1) Tumor Proportion Score (TPS) ≥ 50% (MK-2870-007) (TroFuse-007) – ClinicalTrials.gov ID NCT06170788
A Study to Assess Efficacy and Safety of Pembrolizumab With or Without Sacituzumab Tirumotecan (MK- 2870) in Adult Participants With Resectable Non Small Cell Lung Cancer (NSCLC) Not Achieving Pathological Complete Response (pCR) (MK-2870-019) (TroFuse-019) – ClinicalTrials.gov ID NCT06312137
Sacituzumab Tirumotecan (MK-2870) in Post Platinum and Post Immunotherapy Endometrial Cancer (MK-2870-005) (TroFuse-005) – ClinicalTrials.gov ID NCT06132958
Sacituzumab Tirumotecan (MK-2870) Versus Chemotherapy in Previously Treated Advanced or Metastatic Nonsquamous Non-small Cell Lung Cancer (NSCLC) With EGFR Mutations or Other Genomic Alterations (MK-2870-004) – ClinicalTrials.gov ID NCT06074588
A Clinical Study of MK-2870 Alone or With Chemotherapy to Treat Gastrointestinal Cancers (MK-9999-02A) – ClinicalTrials.gov ID NCT06428409
Efficacy and Safety of SKB264 in Combination With Pembrolizumab in Patients With Initially Unresectable Stage III NSCLC – ClinicalTrials.gov ID NCT06706219
Sacituzumab Tirumotecan (MK-2870) Versus Pemetrexed and Carboplatin Combination Therapy in Participants With Epidermal Growth Factor (EGFR)-Mutated, Advanced Nonsquamous Non-small Cell Lung Cancer (NSCLC) Who Have Progressed on Prior EGFR Tyrosine Kinase Inhibitors (MK-2870-009) – ClinicalTrials.gov ID NCT06305754
Substudy 06C: A Study of Sacituzumab Tirumotecan (MK-2870) With Pembrolizumab (MK-3475) and Chemotherapy in Participants With First-Line Locally Advanced Unresectable/Metastatic Gastroesophageal Adenocarcinoma (MK-3475-06C/KEYMAKER-U06) – ClinicalTrials.gov ID NCT06469944
Substudy 06D: Combination Therapies in Second Line (2L) Gastroesophageal Adenocarcinoma (MK-3475-06D/Keymaker-U06) – ClinicalTrials.gov ID NCT06445972
Pembrolizumab (MK-3475) Plus Investigational Agents in Resectable Non-small Cell Lung Cancer (NSCLC) (MK-3475-01E/KEYMAKER-U01) – ClinicalTrials.gov ID NCT06788912
A Study to Evaluate Investigational Agents With or Without Pembrolizumab (MK-3475) in Participants With Advanced Esophageal Cancer Previously Exposed to Programmed Cell Death 1 Protein (PD-1)/ Programmed Cell Death Ligand 1 (PD-L1) Treatment (MK-3475-06B) – ClinicalTrials.gov ID NCT05319730
Phase I-II, FIH, TROP2 ADC, Advanced Unresectable/Metastatic Solid Tumors, Refractory to Standard Therapies (A264) – ClinicalTrials.gov ID NCT04152499
Highlights of prescribing Information
Osimertinib (Tagrisso®; AstraZeneca)[Prescribing Information]
Reference
[1] Chinese Society of Clinical Oncology (CSCO) (2024)] Guidelines for the diagnosis and treatment of non-small cell lung cancer.
[2] Han B, Zheng R, Zeng H, Wang S, Sun K, Chen R, Li L, Wei W, He J. Cancer incidence and mortality in China, 2022. J Natl Cancer Cent. 2024 Feb 2;4(1):47-53. doi: 10.1016/j.jncc.2024.01.006. PMID: 39036382; PMCID: PMC11256708.
[3] Chinese Society of Clinical Oncology (CSCO) (2024)] Guidelines for the diagnosis and treatment of breast cancer.
[4] Jiang S, Yuan F, Zhou F, Jiang K, Zhang X, Li X, Seneviratne LC, Yu G, Zhang M, Zhang S, Chen M, Blumenthal GM, Akala OO, Li Y, Jing D, Ge J, Shi Y. Efficacy and safety of sacituzumab tirumotecan monotherapy in patients with advanced urothelial carcinoma who progressed on or after prior anti-cancer therapies: Report from the phase 1/2 MK-2870-001 study. (Abstract: #796) Journal of Clinical Oncology 2025 43:5_suppl, 796-796
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