Table 1

Summary of clinical evidence demonstrating TMB as a biomarker for response to immunotherapy

Immunotherapy agent and tumour typeStudy/trial*TMB assay usedType of benefit
 NSCLC (1 L)CheckMate 02652 WESORR, PFS
 NSCLCFlatiron Health117 Foundation CGP panelOS
 Melanoma (1 L or 2 L)CheckMate 03822 WESORR, OS, PFS
 MelanomaCheckMate 06423 WESORR, OS
 BladderCheckMate 27583 WESORR, OS, PFS
 GBMBouffet et al, 2016118 WESDRR
 MelanomaVan Allen et al, 2015119 WESCBR
Snyder et al, 201486 WESCBR, OS
Nivolumab and ipilimumab in combination
 NSCLC (1 L)CheckMate 01235 WESORR, DCB, PFS
 NSCLC (1 L)CheckMate 227†8 FoundationOne CDxORR, PFS
 NSCLC (1 L)CheckMate 5689 FoundationOne CDxORR
 SCLC (2 L)CheckMate 03284 WESORR, OS, PFS
 CRCLe et al, 201544 WESORR, PFS
 Multiple solid tumoursKEYNOTE-012/KEYNOTE-028120 121 WESORR
 NSCLC (2 L)POPLAR/OAK87 88 Foundation bTMBOS, PFS
 NSCLC (1 L)BFAST and B-F1RST122–124 Foundation bTMBDOR, ORR, PFS, OS
 NSCLCRizvi et al, 201856 WESDCB, ORR, PFS
 Bladder (1 L or 2 L)IMvigor 210125 126 Foundation CGP panelORR, OS
 Bladder (2 L)IMvigor 211127 FoundationOneOS
 BladderSnyder et al, 2017128 WESPFS
Multiple agents
 NSCLCRozenblum et al, 2017129 FoundationOne and Guardant360ORR
 MelanomaJohnson et al, 201653 FoundationOneORR, OS, PFS
Hugo et al, 201645 WESOS
 Multiple solid tumoursGoodman et al, 2017130 FoundationOneORR, OS, PFS
Yarchoan et al, 201725 Various (not reported)ORR
 Multiple solid tumours (2 L)Bonta et al, 2017131 FoundationOneORR
  • *Ongoing atezolizumab, durvalumab and avelumab trials have primary completion dates in 2019 and 2020.

  • †CheckMate 227 has monotherapy and combination therapy arms in the study design.

  • CBR, clinical benefit rate; CGP, comprehensive genomic profiling; CRC, colorectal cancer; DCB, durable clinical benefit; DOR, duration of response; DRR, durable response rate; GBM, glioblastoma multiforme; NSCLC, non-small cell lung cancer; ORR, objective response rate; OS, overall survival; PFS, progression-free survival; SCLC, small cell lung cancer; TMB, tumour mutational burden; WES, whole exome sequencing.