FDA Approves Pembrolizumab for TMB-H Solid Tumors: Threshold ≥13 mut/Mb, KEYNOTE-158 Data

　　1.Approval Snapshot

　　On 16 Oct 2026,FDA traditionally approved pembrolizumab(Keytruda)and pembrolizumab+berahyaluronidase alfa-pmph(Keytruda Qlex)for selected TMB-H solid tumor patients.

　　Criteria:

　　adults and children;

　　unresectable or metastatic;

　　TMB≥13 mut/Mb by FDA-recognized test;

　　disease progression after prior therapy,no satisfactory alternative.

　　Not for all advanced solid tumors.

　　2.Why Threshold Changed from 10 to 13 mut/Mb

　　Previous accelerated approval used≥10 mut/Mb.For traditional approval,FDA found efficacy not confirmed in patients with TMB 10 to<13 mut/Mb,thus raised threshold to≥13 mut/Mb.Biomarker cutoffs require rigorous validation.

　　3.Efficacy(KEYNOTE-158)

　　220 patients with TMB≥13 mut/Mb:

　　ORR:36%;

　　among responders,58%had duration≥12 months.

　　ORR is not cure rate;outcomes vary by tumor type and history.

　　4.Dosing

　　Adults:200mg IV every 3 weeks or 400mg every 6 weeks;

　　Children:2mg/kg IV every 3 weeks(max 200mg);

　　Continue until progression,unacceptable toxicity,or 24 months.

　　5.Safety

　　PD-1 inhibitor:immune-mediated adverse reactions possible:

　　pneumonitis,colitis,hepatitis;

　　endocrinopathies(thyroid,pituitary,diabetes);

　　nephritis,infusion reactions;

　　allogeneic HSCT complications,embryo-fetal toxicity.

　　Monitor beyond tumor shrinkage.