Safety, pharmacokinetics, pharmacodynamics and antitumor activity of legubicin in patients with advanced solid tumors, including lung cancer: a phase 1 dose-escalation and expansion trial

BACKGROUND: This first-in-human, phase 1a/b dose escalation and expansion trial investigated the safety and antitumor activities of legubicin, a novel conjugate of doxorubicin with a legumain-cleavable tetrapeptide linker, for patients with advanced solid tumors who failed or had no applicable standard of care treatment. METHODS: Q3W on day 1 of each 3-week cycle in phase 1b. The primary endpoints included safety (phase 1a/b), the maximum tolerated dose and recommended phase 2 dose (RP2D) (phase 1a), and independent review committee (IRC)-assessed antitumor activities of legubicin per RECIST version 1.1 (phase 1b). RESULTS: Q3W had a partial response, and the IRC-confirmed objective response rate was 5.7% (95% CI 0.7%-19.2%). CONCLUSIONS: administered every 2 or 3 weeks, with preliminary signals of antitumor activities in a heterogeneous cohort of patients with pretreated advanced tumors, including heavily pretreated lung cancer patients. These findings support further evaluation in tumor‑specific studies. TRIAL REGISTRATION: Chinese Clinical Trial Registry (http://www.chictr.org.cn/, ChiCTR2600122142; registered on April 9, 2026).