At the 2025 European Society for Medical Oncology (ESMO) Congress, Professor Li Zhang presented the pivotal Phase III OptiTROP‑Lung04 trial evaluating sacituzumab tirumotecan (Sac‑TMT) versus platinum‑based chemotherapy in patients with EGFR‑mutated non‑small cell lung cancer (NSCLC) who had progressed on prior EGFR‑TKI therapy. This multicentre, randomized study enrolled 376 patients, assigning them to receive either Sac‑TMT or standard cisplatin/carboplatin plus pemetrexed.
Sacituzumab Tirumotecan Delivers Survival Advantage
After a median follow‑up of 18.9 months, Sac‑TMT demonstrated a statistically and clinically significant improvement in progression‑free survival (PFS). Median PFS was 8.3 months with Sac‑TMT compared with 4.3 months for chemotherapy (hazard ratio 0.49; P < 0.0001), corresponding to a fourfold higher 12‑month PFS rate (32.3% vs 7.9%). Overall survival (OS) data further favoured Sac‑TMT, with median OS not yet reached at data cut‑off, versus 17.4 months in the chemotherapy arm (HR 0.60; P = 0.0006). Adjusted multivariate analysis confirmed the consistency of OS benefit (HR 0.56; P = 0.0002).
Manageable Safety and Response Rates
Efficacy outcomes were complemented by a robust safety and tolerability profile. Sac‑TMT achieved a superior objective response rate of 60.6% compared with 43.1% for chemotherapy, with median duration of response extending to 8.3 months versus 4.2 months. The incidence of grade ≥ 3 treatment‑related adverse events was comparable between study arms, while serious treatment‑related events and interstitial lung disease were distinctly lower with Sac‑TMT and completely absent in some cases.
Clinical Impact and Future Outlook
Professor Zhang emphasized that Sac‑TMT, featuring a novel belotecan‑derived topoisomerase I payload, represents a breakthrough in TROP2‑directed antibody‑drug conjugate (ADC) development. These findings establish Sac‑TMT as a promising therapeutic candidate capable of delivering meaningful survival benefits with manageable toxicity, positioning it for potential adoption as a future standard‑of‑care for patients with EGFR‑TKI‑resistant NSCLC.
Reference
Zhang L et al. Sacituzumab tirumotecan (sac-TMT) vs platinum-based chemotherapy in EGFR-mutated (EGFRm) non-small cell lung cancer (NSCLC) following progression on EGFR-TKIs: results from the randomized, multi-center phase III OptiTROP-Lung04 study. ESMO 2025, Berlin, Germany.
