*October 2025*
Treatment with Sacituzumab tirumotecan (sac-TMT) led to an improvement in progression-free survival (PFS) vs chemotherapy in patients with nonsquamous non–small cell lung cancer (NSCLC) harboring EGFR mutations who disease was resistant to EGFR-TKIs, according to phase 3 results of the OptiTROP-Lung04 study (NCT05870319) that were presented during 2025 ESMO Congress.1
Results showed that, at a median follow-up of 18.9 months, the median progression-free survival (PFS) via blinded independent central review (BICR) was 8.3 months (95% CI, 6.7-9.9) with sac-TMT and 4.3 months (95% CI, 4.2-5.5) with chemotherapy (HR, 0.49; 95% CI, 0.39-0.62; P <.0001). The 12-month PFS rates were 32.3% (25.5%-39.2%) and 7.9% (95% CI, 4.4%-12.8%), respectively. The PFS benefit with sac-TMT was observed across all prespecified subgroups.
The investigator-assessed median PFS was 8.4 months (95% CI, 7.1-9.7) with sac-TMT and 4.8 months (95% CI 4.2-5.5) with chemotherapy (HR, 0.51; 95% CI, 0.41-0.65; P <.0001). The 12-month PFS rates were 34.7% (27.7%-41.7%) and 10.7% (95% CI, 6.5%-16.0%), respectively.
“Sac-TMT demonstrated statistically significant and clinically meaningful improvements in PFS and OS compared to platinum-based chemotherapy,” lead study author Li Zhang, MD, professor of medical oncology at Sun Yat-sen University Cancer Center in Guangzhou, China, said in an oral presentation of the data. “The results of the OptiTROP-Lung04 study support sac-TMT as a promising new treatment option for patients with EGFR-mutated NSCLC with EGFR-TKI resistance.”
Sac-TMT is a TROP2 antibody-drug conjugate (ADC) with a unique biofunctional linker that maximizes delivery of a belotecan-derivative topo I inhibitor payload to tumor cells. TROP2 is highly expressed in patients with EGFR-mutated NSCLC; preclinical data have shown that sac-TMT internalization and uptake are enhanced by EGFR mutations.2
The current standard option for patients who relapse on third-generation EGFR TKIs remains platinum-based chemotherapy, but more options are needed.
In the multicenter, open-label, phase 3 OptiTROP-Lung04 trial, 376 patients with nonsquamous stage IIIB/IIIC or IV NSCLC with EGFR-sensitive mutations were randomly assigned 1:1 to receive sac-TMT at 5 mg/kg intravenously (IV) every 2 weeks or pemetrexed at 500 mg/m2 plus carboplatin AUC 5 or cisplatin at 75 mg/m2 every 3 weeks for up to 4 cycles, followed by pemetrexed maintenance at 500 mg/m2 every 3 weeks. Treatment was given until disease progression, intolerable toxicity, or patient request to discontinue therapy. Read more.
