Phase I study of the LiViT regimen (liposomal irinotecan, vincristine, and temozolomide) in pediatric patients with relapsed/refractory solid tumors.

Abstract

10039 Background: Relapsed or refractory solid tumors in children and adolescents remain a major therapeutic challenge with limited effective options. Liposomal irinotecan provides prolonged systemic exposure compared to conventional irinotecan and may offer improved efficacy and tolerability. We conducted a phase I trial to determine the recommended phase II dose (RP2D), safety, and preliminary antitumor activity of the LiViT regimen in patients aged 2–18 years. Methods: This single-center, open-label phase I study enrolled patients aged 2–18 years with relapsed/refractory solid tumors. The LiViT regimen consisted of vincristine (1.5 mg/m² IV day 1; max 2 mg), temozolomide (150 mg/m²/day IV days 1–5) and liposomal irinotecan at escalating doses of 40, 50, 65, 80, or 100 mg/m² (IV day 1) every 3 weeks. A standard 3+3 dose-escalation design was used (Ia), followed by an expansion cohort (Ib). Results: Twenty-nine patients were enrolled (Ia: 18; Ib: 11). Diagnoses included rhabdomyosarcoma (n=12), neuroblastoma (n=9), desmoplastic small round cell tumor (n=3), Ewing sarcoma (n=2), and others (n=3). In phase Ia, liposomal irinotecan was administered at escalating doses of 40, 50, 65, 80, and 100 mg/m². At 80 mg/m², 1 of the first 3 patients experienced a dose-limiting toxicity (DLT) (grade 3 diarrhea lasting >3 days despite loperamide); the cohort was expanded to 6 patients, and no additional DLTs or other grade 3–4 toxicities were observed. No DLTs occurred among patients treated at 100 mg/m² during Ia (n=3) or in the Ib expansion cohort (n=11). The MTD was not reached, and 100 mg/m² was selected as the RP2D based on safety in 14 patients. Across all dose levels, the only grade ≥3 treatment-related adverse event was the single episode of grade 3 diarrhea at 80 mg/m²; all other toxicities were grade 1–2. Among 27 evaluable patients, 5 achieved partial response (PR) and 12 had stable disease (SD), yielding an objective response rate (ORR) of 18.5% and a disease control rate (DCR) of 63.0%. Conclusions: The LiViT regimen is feasible with a manageable safety profile in pediatric patients with relapsed/refractory solid tumors. The MTD was not reached, and liposomal irinotecan at 100 mg/m²—the highest tested dose—was established as the RP2D. Promising preliminary activity supports phase II evaluation. Clinical trial information: NCT06710821 .