Treating Non-Small Cell Lung Cancer with mutated EGFR using Sacituzumab Tirumotecan
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Reviewed & Translated by Dat Tien Nguyen, B.A, ScM.
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Posted on February 13th, 2026
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Tumors of patients with non-small cell lung cancer express a high level of receptor for epidermal growth factor (EGFR). Because these receptors are important for tumor proliferation, targeting them with EGFR tyrosine kinase inhibitors (EGFR-TKI) has been an effective strategy to manage the cancer. However, mutation to EGFR can happen, and this leads to resistance against the EGFR-TKI. In these cases, a study was conducted to explore the usage of sacituzumab tirumotecan as an alternative means of treatment.
Funding Source(s): Sichuan Kelun-Biotech Biopharmaceutical
The phase 3 clinical study was conducted in China, and it included 376 participants who had been diagnosed with nonsquamous non-small cell lung cancer. Almost all of the patients were in stage IV disease, with brain & liver metastases occurring in around 15% of the cohort. All of the patients included in the study had mutation to their EGFR, with around 40% having a leucine-to-arginine substitution at residue 858 on exon 21, and 60% having deletion of exon 19. Around 95% of the participants had previously been treated with third-generation EGFR-TKI.
The patients were randomly assigned to be treated intravenously with either the standard combination of pemetrexed plus platinum-based chemotherapy or sacituzumab tirumotecan. This experimental treatment was given at a dose of 5 mg per kilogram of body weight on day 1 and 15 of a 28-day cycle. Sacituzumab tirumotecan is a drug-antibody conjugate, with the antibody targeting trophoblast cell surface antigen 2 (Trop-2) help guide the belotecan-derived topoisomerase I inhibitor drug to the tumor.
After a median follow-up period of 18.9 months, the researchers found that patients treated with sacituzumab tirumotecan reduced the risk of death or disease progression by 51%. Subgroup analyses found that the experimental treatment is effective regardless of EGFR mutation type, as this receptor is not the primary target of the treatment. Additionally, analysis found that the treatment is not as effective in patients with brain metastases, which might indicate that the medication might not be able to penetrate the blood-brain barrier. Besides halting disease progression, tumor shrinkage is more common in patients treated with sacituzumab tirumotecan. However, sacituzumab tirumotecan is associated with a significantly higher frequency of alopecia and stomatitis.
Funding Source(s): Sichuan Kelun-Biotech Biopharmaceutical
The phase 3 clinical study was conducted in China, and it included 376 participants who had been diagnosed with nonsquamous non-small cell lung cancer. Almost all of the patients were in stage IV disease, with brain & liver metastases occurring in around 15% of the cohort. All of the patients included in the study had mutation to their EGFR, with around 40% having a leucine-to-arginine substitution at residue 858 on exon 21, and 60% having deletion of exon 19. Around 95% of the participants had previously been treated with third-generation EGFR-TKI.
The patients were randomly assigned to be treated intravenously with either the standard combination of pemetrexed plus platinum-based chemotherapy or sacituzumab tirumotecan. This experimental treatment was given at a dose of 5 mg per kilogram of body weight on day 1 and 15 of a 28-day cycle. Sacituzumab tirumotecan is a drug-antibody conjugate, with the antibody targeting trophoblast cell surface antigen 2 (Trop-2) help guide the belotecan-derived topoisomerase I inhibitor drug to the tumor.
After a median follow-up period of 18.9 months, the researchers found that patients treated with sacituzumab tirumotecan reduced the risk of death or disease progression by 51%. Subgroup analyses found that the experimental treatment is effective regardless of EGFR mutation type, as this receptor is not the primary target of the treatment. Additionally, analysis found that the treatment is not as effective in patients with brain metastases, which might indicate that the medication might not be able to penetrate the blood-brain barrier. Besides halting disease progression, tumor shrinkage is more common in patients treated with sacituzumab tirumotecan. However, sacituzumab tirumotecan is associated with a significantly higher frequency of alopecia and stomatitis.