Multicenter phase 1 study of spartalizumab plus low-dose pazopanib for pediatric relapsed/refractory tumors

The initial results of immunotherapy in children with relapsed/refractory (R/R) tumors have been disappointing. Modulation of angiogenesis with anti-VEGF may enhance immunotherapy penetration. The multicenter phase 1 SPARTO trial in France evaluated the combination of spartalizumab (anti-PD-1) and low-dose pazopanib for pediatric R/R tumors. Forty-one patients (median age 13.9 years; range 7-25) were enrolled and received spartalizumab at three dose levels (2, 3, or 4 mg/kg once every 4 weeks) in combination with pazopanib 225 mg/m² daily. Among 40 evaluable patients, 58 grade 3-4 adverse events were reported in 26 patients. Dose level 4 mg/kg once every 4 weeks was identified as the recommended phase 2 dose. One patient with osteosarcoma had complete response, 4 patients had partial response (2 osteosarcoma, 1 chordoma, 1 carcinoma) and 8 had stable disease (including 4 longer than 4 months). The median duration was 68 days (IQR 57-106); one patient completed 24 cycles, and two were still on treatment at data cut-off (at cycle 16 and cycle 23). The authors conclude that spartalizumab combined with low-dose pazopanib was well tolerated and showed evidence of antitumor activity in pediatric sarcoma, especially osteosarcoma.