Background: In the phase 1 portion of KEYNOTE-051 (NCT02332668), the 2-mg/kg-Q3W dose of pembro was identified as the pediatric recommended phase 2 dose. We provide an update on the safety and efficacy of this dose by tumor type in the ongoing phase 2 trial. Methods: Pts aged 6 mo to < 18 y with advanced melanoma or a PD-L1–positive, advanced relapsed/refractory solid tumor or lymphoma and measurable disease per RECIST v1.1 received pembro 2 mg/kg Q3W until confirmed disease progression per irRECIST by investigator review, intolerable toxicity, or pt/investigator decision to discontinue. Key efficacy end points were ORR and PFS per RECIST v1.1 by investigator and OS (data cutoff Oct 10, 2017). Results: 689 of 748 prescreened pts had PD-L1–evaluable tumors. Of these, 229 (33.2%) were PD-L1–positive; 125 pts (median age, 13 y [range, 1-17]) were enrolled and treated (10 Hodgkin lymphoma [HL]; 115 other tumors). Median follow-up was 5.7 mo (range, 0.2-29). Primary diagnoses were other non–central nervous system (CNS) solid tumors (46%), sarcoma (19%), CNS tumors (26%), and lymphoma (9%). Seven (6%) pts experienced grade 3-5 treatment-related AEs; of these, 2 (1.6%) discontinued (1 due to increased aspartate aminotransferase; 1 with renal medullary carcinoma died of treatment-related pulmonary edema). No major untoward effects on the developing immune system were observed. One pt (10.0%) with HL achieved CR and 5 (50%) achieved PR. Six (5.2%) pts with other tumors achieved prolonged PR (2 adrenocortical carcinoma and 1 each epithelioid sarcoma, mesothelioma, malignant ganglioglioma, and lymphoepithelial carcinoma). ORR was 60.0% (95% CI, 26.2-87.8) in pts with HL and 5.2% (95% CI, 1.9-11.0) in pts with all other tumor types. Median PFS was 12.2 mo in HL and 1.9 mo in any other tumor type; 12-mo PFS was 56.3% and 8.3%, respectively. Four (40.0%) pts with HL and 19 (16.5%) with any other tumor type survived ≥12 months. Conclusions: Pembro was well tolerated and showed response in HL and in a few rare tumor types, which warrants further study. Enrollment in KEYNOTE-051 is ongoing. Clinical trial information: NCT02332668