Trial results for a Phase 1 study (NCT05063318) investigating lurbinectedin in patients with advanced solid tumors were posted on ClinicalTrials.gov on 2025-09-02. The study found that co-administration with itraconazole increased lurbinectedin's dose-adjusted AUC(0-∞) by a geometric mean ratio of 272.73% compared to lurbinectedin alone.
Background
This study focused on patients with advanced solid tumors, investigating the pharmacokinetic profile of lurbinectedin both alone and when co-administered with itraconazole.
Trial design
The study (NCT05063318) was a Phase 1b, prospective, open-label, two-way crossover drug-drug interaction study. It enrolled 14 participants with advanced solid tumors. The interventions included lurbinectedin alone and lurbinectedin+itraconazole co-administration, designed to assess the impact of itraconazole on lurbinectedin's pharmacokinetics.
Key results
The trial results demonstrated significant changes in lurbinectedin's pharmacokinetic parameters when co-administered with itraconazole:
- For Dose-adjusted AUC(0-∞), the geometric mean was 105.8 μg·h/L/mg (Geometric Coefficient of Variation: 77.37%) for lurbinectedin alone, compared to 288.55 μg·h/L/mg (Geometric Coefficient of Variation: 73.9%) for ITZ+LRB. The least-squares geometric mean ratio was 272.73 (90.0% CI: 213.22 to 348.86).
- For Dose-normalized AUC(0-t), the geometric mean was 103.4 μg·h/L/mg (Geometric Coefficient of Variation: 78.85%) for lurbinectedin alone, compared to 244.77 μg·h/L/mg (Geometric Coefficient of Variation: 91.89%) for ITZ+LRB. The least-squares geometric mean ratio was 236.73 (90.0% CI: 177.35 to 316.0).
- Dose-normalized Cmax showed a geometric mean of 22.43 μg/L/mg (Geometric Coefficient of Variation: 53.75%) for lurbinectedin alone, versus 25.91 μg/L/mg (Geometric Coefficient of Variation: 53.15%) for ITZ+LRB. The least-squares geometric mean ratio was 115.51 (90.0% CI: 100.07 to 133.33).
- The half-life (T1/2) increased from a geometric mean of 46.59 hours (Geometric Coefficient of Variation: 17.12%) for lurbinectedin alone to 101.36 hours (Geometric Coefficient of Variation: 61%) for ITZ+LRB. The least-squares geometric mean ratio was 217.57 (90.0% CI: 151.81 to 311.82).
- Total Body Clearance (CL) decreased from a geometric mean of 9.45 L/h (Geometric Coefficient of Variation: 77.37%) for lurbinectedin alone to 3.47 L/h (Geometric Coefficient of Variation: 73.9%) for ITZ+LRB. The least-squares geometric mean ratio was 36.67 (90.0% CI: 28.66 to 46.9).
What this means
The results indicate that co-administration of lurbinectedin with itraconazole significantly increases lurbinectedin's systemic exposure and prolongs its half-life, while decreasing its total body clearance. Itraconazole is known to be a strong inhibitor of CYP3A4, an enzyme involved in drug metabolism. These pharmacokinetic changes suggest a potential for increased systemic concentrations of lurbinectedin when taken concurrently with strong CYP3A4 inhibitors, which could necessitate dose adjustments to manage potential toxicity in patients with advanced solid tumors.
Source
The information regarding these trial results was obtained from ClinicalTrials.gov, a public database of clinical studies. The results for study NCT05063318, titled "Clinical Trial of Lurbinectedin (PM01183) in Patients With Advanced Solid Tumors," were posted on 2025-09-02 on clinicaltrials.gov.