Table 2.
CRC clinical trials potentially targeting Treg cell populations.
| Clinical trial | Antibody target | n CRC patients and tumor type | Response to treatment | PFS | OS | Comments and references |
|---|---|---|---|---|---|---|
|
NCT01876511 (Phase II) |
anti-PD-1 pembrolizumab (MK-3475, SCH 900475) | 10 metastatic MSI CRC patients 11 metastatic MSS CRC patients |
40% MSI ORR 0% MSS ORR |
78% MSI 11% MSS |
This findings drove FDA-approval for the treatment of unresectable, metastatic MSI-H and dMMR (218) | |
| NCT00441337 (Phase I) | anti-PD-1 nivolumab (BMS-936558, MDX-1106, ONO-4538) | 14 metastatic MSI or MSS CRC patients | 1 MSI CR ≥ 21 months |
Followed up in: NCT02060188 (phase II) (219) |
||
|
NCT02060188 (Phase II) |
anti-PD-1 nivolumab | 74 refractory metastatic dMMR/MSI-H CRC patients |
23 patients PR 31% ORR 69% DCR ≥ 12 weeks |
50% ≥ 12 months |
73% ≥ 12 months |
This findings drove FDA-approval for the treatment of refractory MSI-H/dMMR CRC (212) |
| anti-PD-1 nivolumab in combination with anti-CTLA-4 ipilimumab (IgG1 isotype) | 119 refractory metastatic dMMR/MSI-H CRC patients |
55% ORR 80% DCR ≥ 12 weeks |
71% ≥ 12 months |
85% ≥ 12 months |
Combination therapy improves therapeutic efficacy for dMMR/ MSI-H CRC (220) |
|
|
NCT00313794 (Phase II) |
anti-CTLA-4 tremelimumab (CP-675,206 or ticilimumab) | 47 refractory metastatic CRC patients Subtype not determined |
45 response-evaluable patients | 2% 15 months before relapse |
45% ≥ 6 months |
No clinically meaningful but interesting for combinational approaches (221) |
|
NCT02870920 (Phase II) |
anti-CTLA-4 tremelimumab and anti-PD-L1 durvalumab | 180 pre-treated-refractory MSS or proficient MMR CRC patients | 1.8 months | 6.6 months | Combination therapy improves the OS and quality of life of patients with advanced refractory CRC but not dMMR CRC (222) | |
|
NCT03101475 (Phase II) |
anti-CTLA-4 tremelimumab and anti-PD-L1 durvalumab | Currently, 22 metastatic CRC patients | Ongoing clinical trial | |||
|
NCT02794571 (Phase I) |
anti-TIGIT (MTIG7192A) as monotherapy or in combination with anti-PD-L1 atezolizumab | Recruiting advanced incurable tumors, including CRC patients | Ongoing clinical trial | |||
|
NCT01968109 (Phase I/IIa) |
anti-LAG-3 relatlimab (BMS-986016) as monotherapy or in combination with anti-PD1 nivolumab | Recruiting advanced solid tumors including CRC patients | Ongoing clinical trial | |||
|
NCT03156114 (Phase I) |
anti-LAG-3 miptenalimab (BI 754111) as monotherapy or in combination with anti- PD-1 ezabenlimab (BI 75409111) | Recruiting advanced solid tumors including metastatic CRC patients | Ongoing clinical trial | |||
|
NCT02608268 (Phase I/II) |
anti-TIM-3 (MBG453) with anti-PD-1 spartalizumab (PDR001) | 6 metastatic CRC patients | 2 partially responded | Ongoing clinical trial (223) |
||
|
NCT02817633 (Phase I) |
anti-TIM-3 (TSR-022) as monotherapy or in combination with anti- PD-1 dostarlimab (TSR-042) | Recruiting advanced solid tumors including CRC patients | Ongoing clinical trial | |||
|
NCT02705105 (Phase I/II) |
anti-CCR4
mogamulizumab as monotherapy or in combination with anti- PD-1 nivolumab |
29 MSS CRC patients | 0 ORR with monotherapy 1 ORR with combination therapy |
No enhanced efficacy of the combination therapy compared to monotherapy with nivolumab (224) |
PFS, progression-free survival; OS, overall survival; MSI, microsatellite instability tumors; MSS, microsatellite stable tumors; dMMR, different mismatch-repair; ORR, overall response rate; PR, Partial response; CR, Complete response; DCR, disease control rate; BSC, best supportive care.