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Table 2. Ongoing clinical trials of immunotherapy in colorectal cancer
Trial Phase Drugs Setting Number of
identifier
MK-3475-177/KEYNOTE-177 III Pembrolizumab 200 mg each 21 days for up to 35 1st line NCT02563002
Ongoing (not recruiting) treatments vs. chemotherapy
Estimated primary completion date August 15, 2019
A Study to Investigate Efficacy and Safety of III Regorafenib (160 mg days 1-21 every 28 days) vs. 3rd line NCT 02788279
Cobimetinib Plus Atezolizumab and Atezolizumab Cobimetinib plus atezolizumab (cobimetinib 60 mg days
Monotherapy vs. Regorafenib in Participants With 1 to 21 plus atezolizumab 840 mg IV on day 1 and day
Metastatic Colorectal Adenocarcinoma (COTEZO 15 in a 28-day cycle) and atezolizumab monotherapy
IMblaze370) (atezolizumab monotherapy 1,200 milligrams (mg) on
Ongoing, (not recruiting) day 1 in a 21-day cycle
Estimated primary completion date February 2019
A Phase 2 Study With Safety Lead-in, Evaluating II TAS102 plus Nivolumab 3rd line NCT02860546
TAS-102 Plus Nivolumab in Patients With
Microsatellite Stable Refractory Metastatic
Colorectal Cancer
Ongoing (not recruit)
Estimated completation date March 2018
MK-3475-158/KEYNOTE-158 II Pembrolizumab 200 mg every 3 weeks for up to 35 Pre- NCT02628067
Ongoing (recruiting) administrations treated
Estimated primary completion date August 28,
2023
Phase 2 Study of MK-3475 in Patients With II -MSI Negative Colorectal Cancer: Pembroluzumab Pre- NCT01876511
Microsatellite Unstable (MSI) Tumors 10 mg/kg every 14 days treated
Ongoing (recruiting) -MSI Negative with Mutator Phenotype: Pembrolizumab
Estimated primary completion date 200 mg flat dose every 21 days
June 2021
A Phase I, Open-Label, Multi-Centre Study to I Selumetinib + MEDI4736 Pre- NCT02586987
Assess the Safety, Tolerability and Preliminary Anti- Patients with known MSI-high status will be excluded; treated
tumour Activity of Ascending Doses of Selumetinib patients with MSS, MSI-low, or unknown MSI status
(AZD6244 Hyd-sulfate) in Combination With may be enrolled
MEDI4736 and Selumetinib in Combination With
MEDI4736 and Tremelimumab in Patients With
Advanced Solid Tumours
Ongoing (recruiting)
Estimated primary completion date
July 10, 2018
An Open-label, Phase II Basket Study of a II Azacitidine 300 mg daily for 14 consecutive days of Pre- NCT02811497
hypoMEThylating Agent Oral Azacitidine and every 28 days cycle for 3 cycles. PLUS treated
DURvalumab (MEDI4736) (Anti-PDL1) in Advanced Durvalumab 1,500 mg on Day 1 of every 28 days cycle
Solid Tumors (METADUR) for 12 months or until disease progression
Ongoing (recruiting) Only Microsatellite Stable Colorectal Carcinoma
Estimated primary completion date
July 2021
Evaluate the Efficacy of MEDI4736 in Immunological II subjects will receive MEDI4736 for 12 months, or until 3rd line NCT02227667
Subsets of Advanced Colorectal Cancer PD, initiation of alternative cancer therapy, unacceptable
Ongoing (recruiting) toxicity. Following the 12-month treatment period,
Estimated primary completion date subjects without evidence for PD or other reason to
July 2019 discontinue treatment will be monitored without further
treatment. Upon evidence of PD during the monitoring
period, administration of MEDI4736 may resume at the
Q2W schedule, for up to another 12 months
Locally advanced or metastatic MSI-H CRC
*Preliminary data; MSI: microsatellite instable; MSS: microsatellite stable; TAS: Trifluridine/Tipiracil; PD: progressive disease; PDL-1:
programmed cell death ligand-1; CRC: colorectal cancer

could be useful for all CRC if it was possible to convert the tumor towards a “CMS1-like” immune
phenotype. CMS4 tumors (which showed the worse prognosis in terms of overall and relapse-free survival),
for example, are characterized by an unfavorable, inflammed immune phenotype. They revealed high
expression of mesenchymal genes, stromal cell infiltration and an angiogenic microenvironment.

Vascular endothelial growth factor-A (VEGF-A), a proangiogenic molecule produced by the tumors, has
[39]
a crucial role in the development of the immunosuppressive microenvironment . Given the immune-
adjuvant effect that has been suggested for metastatic CRC patients treated with the anti-VEGF antibody