Pembrolizumab in pediatric participants with relapsed or refractory microsatellite instability-high solid tumors: Results from the phase 1/2 KEYNOTE-051 trial.

10040 Background: KEYNOTE-051 (NCT02332668) is an open-label, multicohort, phase 1/2 study evaluating pembrolizumab in children with advanced cancers. Results from participants with melanoma, PD-L1–positive solid tumors, or PD-L1–positive lymphomas showed pembrolizumab had a manageable safety profile, encouraging antitumor activity in relapsed or refractory (R/R) Hodgkin lymphoma, and limited efficacy in most other tumor types. Here, we present results from the cohort of participants with R/R microsatellite instability–high (MSI-H) solid tumors. Methods: Eligible participants were aged 6 months to <18 years and had advanced R/R MSI-H solid tumors determined locally by immunohistochemistry or polymerase chain reaction, measurable disease per RECIST v1.1, and a performance status of ≥50. All participants received pembrolizumab 2 mg/kg (up to a maximum of 200 mg) every 3 weeks for up to 35 doses or until other discontinuation criteria were met. The primary end points were safety and objective response rate (ORR) per RECIST v1.1 by investigator. Secondary end points included duration of response, disease control rate (DCR), and progression-free survival (PFS) per RECIST v1.1, and overall survival (OS). Results: Seven participants with MSI-H solid tumors were enrolled and received treatment. At the data cutoff (Jan 18, 2022), 6 had discontinued treatment and 1 was ongoing. Median age was 11.0 years (range, 3-16), 5 were female, 6 had a central nervous system malignancy (glioblastoma, n = 4; anaplastic astrocytoma, n = 1; high-grade glioma, n = 1), and 1 had an adenocarcinoma. Median time from first dose to data cutoff was 27.6 months (range, 0.3-47.5). Treatment-related AEs occurred in 3 participants; grade 3 or 4 events occurred in 1 participant and included grade 4 lymphocyte count decreased and grade 3 pyrexia. No participants died due to AEs. The ORR per RECIST v1.1 was 0% (95% CI, 0-41); the DCR was 14% (95% CI, 0-58), with 1 participant with adenocarcinoma exhibiting stable disease. Among 6 participants with a postbaseline assessment, 2 had any reduction from baseline in target tumor size, of whom 1 had a reduction of ≥30%. Median PFS was 1.7 months (95% CI, 0.4-NR); 6-month PFS was 17%. Median OS was 7.7 months (95% CI, 1.9-NR); 6-month OS was 50%. One participant with glioblastoma had a complete response at cycle 6 after initial progression, and the complete response was maintained through cycle 20. Conclusions: The safety profile of pembrolizumab in children with MSI-H R/R solid tumors was manageable and consistent with other tumor types. One participant with glioblastoma had a prolonged complete response after initial progression. Further evaluation of pembrolizumab in pediatric MSI-H central nervous system malignancies is ongoing. Clinical trial information: NCT02332668 .