Table 1.
Author | Trial phase | Therapy | Patient population | Objective response rate | Overall survival | Progression-free survival | Other findings |
---|---|---|---|---|---|---|---|
Le et al. [43] | Phase II non-randomized, 3 centers | Pembrolizumab (anti PD-1) 10 mg/kg IV every 14 days |
|
|
|
|
High somatic mutation load associated with prolonged PFS (P = 0.02). |
Topalian et al. [37] | Phase I | Nivolumab (anti PD-1) at doses of 1, 3, or 10 mg/kg every 2 weeks (in dose escalation phase) | Heavily pre-treated, metastatic CRC (n = 17 patients) | CR: 1 patient | - | - | The only responding patient had deficient MMR and PD-L1 positive tumor |
Brahmer et al. [44] | Phase I | BMS-936559 (anti PD-L1) at doses of 0.3, 1, 3, and 10 mg/kg on days 1, 15, and 29 of 6-week cycle | Pre-treated, metastatic CRC (n = 18 patients) | No objective responses | - | - | - |
Herbst et al. [40, 45] | Phase I | MPDL3280A (anti-PD-L1) at doses of≤1, 3, 10, 15 and 20 mg/kg IV every 3 weeks | Pretreated CRC (n = 4 patients) | PR: 1 patient | - | Ongoing response at 60 weeks | Patient post-treatment after 48 weeks |
Bendell et al. [46] | Phase Ib |
|
|
|
- | For responders, PFS range 10–61 weeks | Combinations well tolerated. No worsening of bevacizumab or chemotherapy-associated adverse events. |
Chung et al. [55] | Phase 2, single-arm, multicenter | Tremelimumab (anti-CTLA-4) 15 mg/kg IV on day 1 of every 90-day cycle. | Metastatic CRC, pretreated with any or combination of 5-FU, oxaliplatin, irinotecan and cetuximab (n = 47 patients) |
|
4.8 months (95% CI, 4.1 to 7.7 months) | PFS : 2.3 months (95% CI, 2.1–2.6 months) | No clinically meaningful single-agent activity |
CR = complete response; CRC = colorectal cancer; CTLA-4 = cytotoxic T-lymphocyte-associated protein 4; IV = intravenous; L1 = programmed death ligand 1; OS = overall survival; PD = progressive disease; PD-1 = programmed death 1; PD-MMR = mismatch repair; PFS = progression-free survival; PR = partial response; RR = response rate; SD = stable disease