Table 1. List of studies evaluating different strategies of immunotherapy in metastatic MSS CRC.
| Author, Year | Strategy | Participants | Outcomes |
|---|---|---|---|
| Immunotherapy alone | |||
| Brahmer et al (2010) | Phase I MDX-1106 (anti-PD1) |
Various tumours 14/39 MSS CRC |
1 CR, 2 PR |
| Overman et al (2016) | Phase II – CheckMate-142 Nivolumab + ipilimumab |
28/83 MSS CRC | PFS 1.4 m |
| Chen et al (2020) | Phase II – CO.26 trial Durvalumab + tremelimumab |
180, all MSS CRC | PFS 1.8 m |
| Garralda et al (2021) | Phase I Pembrolizumab + favezelimab |
109, all MSS CRC | ORR 6.3% PFS 2.1 m |
| Bullock et al (2023) | Phase Ib Balstilimab + botensilimab |
101, all MSS CRC | ORR 23% (without CRLM) versus 0% (with CRLM) |
| Immunotherapy combined with other systemic therapies | |||
| Hellman et al (2019) | Phase Ib Atezolizumab + cobimetinib |
Various tumours 84/152 MSS CRC |
ORR 8% |
| Eng et al (2019) | Phase III – IMBlaze-370 Atezolizumab + comibetinib versus regorafenib |
363, all MSS CRC | ORR 3% OS 8.8 versus 8.5 m p 0.99 |
| Cousin et al (2020) | Phase II – REGOMUNE Avelumab + regorafenib |
48, all MSS CRC | ORR 0% PFS 3.6 m |
| Gomez-Roca et al (2021) | Phase II – LEAP005 Pembrolizumab + lenvatinib |
Various tumours 32/187 MSS CRC |
ORR 22% PFS 2.3 m |
| Barzi et al (2022) | Phase I/II Pembrolizumab + regorafenib |
73, all MSS CRC | ORR 0% PFS 2 m |
| Saeed et al (2023) | Phase I – CAMILLA Durvalumab + cabozantinib |
Various tumours 17/35 MSS CRC |
ORR 23.5% PFS 4.6 m |
| Fakih et al (2023) | Phase II – REGONIVO Nivolumab + regorafenib |
70, all MSS CRC | ORR 7% PFS 1.8 m |
| Kawazoe et al (2023) | Phase III – LEAP017 Pembrolizumab + lenvatinib versus regorafenib or TFD/TPI |
480, all MSS CRC | ORR 10.4% versus 1.7% OS 9.8 versus 9.2 m p 0.0379 |
| Immunotherapy combination with locoregional treatments | |||
| Wang et al (2020) | Pilot study Durvalumab + tremelimumab + radioembolization |
9 all, MSS CRC | ORR 0% Closed for futility |
| Wang et al (2021) | Retrospective Immunotherapy ± CRLM resection |
95 all, MSS CRC | PFS 3 versus 1.5 m |
| Parikh et al (2021) | Phase II Nivolumab + ipilimumab + radiotherapy |
Various Tumours 40/65 MSS CRC |
ORR 2.5%–10% |
CR, Complete response; PR, Partial response; ORR, Objective response ratio; PFS, Progression free survival; OS, Overall survival; MSS, Microsatellite stable; CRC, Colorectal cancer, CRLM, Colorectal liver metastasis