BMC cancer · 2026
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.
СтатьяКлиническое исследование I фазыМногоцентровое исследованиеНазвание и аннотация: Перевод в очереди
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Lin Fengjuan, Xue Junli, Li Qun, Tang Wenbo, Zhao Wei, Xue Liqiong, Zhou Jiuli, Liu Yuan, Jin Wenyue, Sun Hui, Liu Cheng, Guo Ye, Li Jin
Аннотация
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: Eligible patients received legubicin over 7 dose levels from 20 mg/m2 to 360 mg/m2 every 3 weeks (Q3W) in phase 1a and legubicin 270 mg/m2 every 2 weeks (Q2W) on day 1 and 15 of each 4-week cycle or legubicin 270 mg/m2 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: Phase 1a enrolled 28 patients (median age 57.5 years; men 60.7% [17/28]) and phase 1b enrolled 35 (median age 53.0 years, men 51.4% [18/35]), with 15 in the 270 mg/m2 Q2W cohort and 20 in the 270 mg/m2 Q3W cohort. All patients received prior antitumor therapy and 32 (91.4%) in phase 1b received ≥ 3 prior lines of therapy. All patients in phase 1a had any-grade treatment-emergent adverse events (TEAEs), including grade 3 or worse TEAEs in 35.7% (10/28). No maximum tolerated dose was established; the RP2D of legubicin was 270 mg/ m2 Q2W or Q3W. Thirty-four patients (97.1%) in phase 1b had any-grade TEAEs. Grade 3 or worse TEAEs occurred in 37.1% (13/35) of the patients, including neutrophil count decreased (25.7% [9/35]), leucocyte count decreased (20.0% [7/35]), and anemia (11.4% [4/35]). At the phase 1b data cutoff, 1 patient with lung cancer receiving legubicin 270 mg/ m2 Q2W and 1 with ovarian cancer receiving legubicin 270 mg/ m2 Q3W had a partial response, and the IRC-confirmed objective response rate was 5.7% (95% CI 0.7%-19.2%).
CONCLUSIONS: Legubicin is safe and well tolerated at a dose of 270 mg/m2 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).
METHODS: Eligible patients received legubicin over 7 dose levels from 20 mg/m2 to 360 mg/m2 every 3 weeks (Q3W) in phase 1a and legubicin 270 mg/m2 every 2 weeks (Q2W) on day 1 and 15 of each 4-week cycle or legubicin 270 mg/m2 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: Phase 1a enrolled 28 patients (median age 57.5 years; men 60.7% [17/28]) and phase 1b enrolled 35 (median age 53.0 years, men 51.4% [18/35]), with 15 in the 270 mg/m2 Q2W cohort and 20 in the 270 mg/m2 Q3W cohort. All patients received prior antitumor therapy and 32 (91.4%) in phase 1b received ≥ 3 prior lines of therapy. All patients in phase 1a had any-grade treatment-emergent adverse events (TEAEs), including grade 3 or worse TEAEs in 35.7% (10/28). No maximum tolerated dose was established; the RP2D of legubicin was 270 mg/ m2 Q2W or Q3W. Thirty-four patients (97.1%) in phase 1b had any-grade TEAEs. Grade 3 or worse TEAEs occurred in 37.1% (13/35) of the patients, including neutrophil count decreased (25.7% [9/35]), leucocyte count decreased (20.0% [7/35]), and anemia (11.4% [4/35]). At the phase 1b data cutoff, 1 patient with lung cancer receiving legubicin 270 mg/ m2 Q2W and 1 with ovarian cancer receiving legubicin 270 mg/ m2 Q3W had a partial response, and the IRC-confirmed objective response rate was 5.7% (95% CI 0.7%-19.2%).
CONCLUSIONS: Legubicin is safe and well tolerated at a dose of 270 mg/m2 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).