Table 3:
Immunotherapy trials in MSI-H/MMR-D Cancer
| Phase 2: completed studies | |||||
|---|---|---|---|---|---|
| Reference | Trial | Regimen | Patient population | Outcomes: % (95% CI) | FDA approval |
| Le et al. (2015)66 |
NCT01876511 Phase 2 (n=41) |
Pembrolizumab | Treatment refractory metastatic: MMR-D CRC (n=11); MMR-P CRC (n=21); MMR-D non-CRC (n=9) |
• ORR for MMR-D CRC: 40% (12-74) • mOS for MMR-D CRC: not met |
5/2017 for refractory metastatic MSI-H/ MMR-D cancers, regardless of primary site |
| Le et al. (2017)67 |
NCT01876511 Phase 2 (n=86) |
Pembrolizumab | Treatment refractory metastatic MMR-D/MSI-H tumors (12 cancer types) | • ORR: 53% (42-54) • mOS: not met • 2 year OS: 64% (53-78) |
As above |
| Overman et al. (2017)57 | CheckMate -142 NCT02060188 Phase 2 (n=74) |
Nivolumab | ≥1 line prior therapy recurrent/metastatic MMR-D CRC | • ORR: 69%(57-79) • mOS: not met • 1 year OS: 73% (62-82) |
7/2017 for refractory MMR-D/MSI-H mCRC |
| Overman et al. (2017)56 | CheckMate -142 NCT02060188 Phase 2 (n=119) |
Nivolumab + Ipilimumab | ≥1 line prior therapy recurrent/metastatic MMR-D CRC | • ORR (55%. 45.2-63.8) • mOS: not met • 1 year OS: 85% (CI 77.0-90.2) |
7/2018 for 2nd line MMR-D/MSI-H mCRC |
| Phase 3: ongoing trials | ||||
|---|---|---|---|---|
| Trial | Regimen | Patient population | Outcomes (pending) | Expected completion |
| KEYNOTE-17 NCT02563002 Phase 3 (n=308) |
Pembrolizumab vs standard of care (6 regimens) | 1st line MMR-D/MSI-H mCRC | • PFS • OS • ORR |
September 19, 2019 |
|
NCT02912559 Phase 3 (n=700) |
Atezolizumab + FOLFOX vs FOLFOX alone | Stage III MMR-D CRC (adjuvant) | • DFS • OS • AE |
July 1, 2020 |
| Immunotherapy: mechanism of action | ||
|---|---|---|
| Name | Brand name (company) | Mechanism of action |
| Atezolizumab | Tecentriq (Genentech/Roche) | humanized, monoclonal antibody that binds to Programmed Death Ligand 1 (PD-L1) |
| Ipilimumab | Yervoy (Bristol-Myers Squibb) | humanized, monoclonal antibody that binds to Programmed Death Ligand 1 (PD-L1) |
| Nivolumab | Opdivo (Bristol-Myers Squibb) | humanized IgG4 antibody targeting the immune checkpoint programmed death receptor-1 (PD-1) |
| Pembolizumab | Keytruda (Merck and Co. Inc.) | humanized monoclonal antibody against PD-1 receptor. |
CI, confidence interval; CRC, colorectal cancer; DFS, disease free survival; F, female; FOLFOX, combination chemotherapy: 5-fluorouracil (5-FU), leucovorin, oxaliplatin; M, male; mCRC: metastatic colorectal cancer; MMR-D, mismatch repair deficient; MMR-P, mismatch repair proficient; mOS, median overall survival; MSI-H, microsatellite instability – high; ; ORR, objective response rate; PFS, progression free survival;