Table 1.
Summary of clinical evidence demonstrating TMB as a biomarker for response to immunotherapy
| Immunotherapy agent and tumour type | Study/trial* | TMB assay used | Type of benefit |
| Nivolumab | |||
| NSCLC (1 L) | CheckMate 02652 | WES | ORR, PFS |
| NSCLC | Flatiron Health117 | Foundation CGP panel | OS |
| Melanoma (1 L or 2 L) | CheckMate 03822 | WES | ORR, OS, PFS |
| Melanoma | CheckMate 06423 | WES | ORR, OS |
| Bladder | CheckMate 27583 | WES | ORR, OS, PFS |
| GBM | Bouffet et al, 2016118 | WES | DRR |
| Ipilimumab | |||
| Melanoma | Van Allen et al, 2015119 | WES | CBR |
| Snyder et al, 201486 | WES | CBR, OS | |
| Nivolumab and ipilimumab in combination | |||
| NSCLC (1 L) | CheckMate 01235 | WES | ORR, DCB, PFS |
| NSCLC (1 L) | CheckMate 227†8 | FoundationOne CDx | ORR, PFS |
| NSCLC (1 L) | CheckMate 5689 | FoundationOne CDx | ORR |
| SCLC (2 L) | CheckMate 03284 | WES | ORR, OS, PFS |
| Pembrolizumab | |||
| NSCLC (1 L) | KEYNOTE-00136 | WES | ORR, DCB, PFS |
| CRC | Le et al, 201544 | WES | ORR, PFS |
| Multiple solid tumours | KEYNOTE-012/KEYNOTE-028120 121 | WES | ORR |
| Atezolizumab | |||
| NSCLC (2 L) | POPLAR/OAK87 88 | Foundation bTMB | OS, PFS |
| NSCLC (2 L) | POPLAR/FIR/BIRCH85 | FoundationOne | ORR, OS, PFS |
| NSCLC (1 L) | BFAST and B-F1RST122–124 | Foundation bTMB | DOR, ORR, PFS, OS |
| NSCLC | Rizvi et al, 201856 | WES | DCB, ORR, PFS |
| Bladder (1 L or 2 L) | IMvigor 210125 126 | Foundation CGP panel | ORR, OS |
| FoundationOne | ORR | ||
| Bladder (2 L) | IMvigor 211127 | FoundationOne | OS |
| Bladder | Snyder et al, 2017128 | WES | PFS |
| Multiple agents | |||
| NSCLC | Rozenblum et al, 2017129 | FoundationOne and Guardant360 | ORR |
| Melanoma | Johnson et al, 201653 | FoundationOne | ORR, OS, PFS |
| Hugo et al, 201645 | WES | OS | |
| Multiple solid tumours | Goodman et al, 2017130 | FoundationOne | ORR, OS, PFS |
| Yarchoan et al, 201725 | Various (not reported) | ORR | |
| Multiple solid tumours (2 L) | Bonta et al, 2017131 | FoundationOne | ORR |
*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.