Table 3.

Ongoing molecularly guided clinical trials in mCRC

Trial name/identifier	Title	Phase	Status	Molecular selection	Experimental arm	Comparator arm
FOCUS4 EudraCT: 2012-005111-12	Molecular selection of therapy in colorectal cancer: a molecularly stratified randomised controlled trial programme	NR	FOCUS4-A: In development FOCUS4-B: Active, not recruiting FOCUS4-C: Recruiting FOCUS4-D: Active, not recruiting FOCUS4-N: Recruiting	Mutations in BRAF, PIK3CA, RAS and TP53 or MSI/dMMR	Dependent on molecular selection	Dependent on molecular selection
KEYNOTE-177 NCT02563002	A Phase III study of pembrolizumab (MK-3475) vs chemotherapy in microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) stage IV colorectal carcinoma	III	Active, not recruiting	MSI-H/dMMR	Pembrolizumab	Standard of care
NCT02982694	A Phase II open-label study with the anti-PD-L1 atezolizumab monoclonal antibody in combination with bevacizumab in patients with advanced chemotherapy resistant colorectal cancer and MSI-like molecular signature	II	Recruiting	MSI	Atezolizumab and bevacizumab	NA
NCT01703390	Pilot study: biomarker directed treatment in metastatic colorectal cancer	II	Recruiting	ERCC1	ERCC1 low: mFOLFOX6 + cetuximab ERCC1 high: FOLFIRI + cetuximab	NA
S1613 NCT03365882	A randomized Phase II study of trastuzumab and pertuzumab (TP) compared to cetuximab and irinotecan (CETIRI) in advanced/metastatic colorectal cancer (mCRC) with HER-2 amplification	II	Recruiting	HER2	Pertuzumab, trastuzumab	Cetuximab, irinotecan hydrochloride
NCT03549338	A Phase II, randomised, open-label, multicentre, three-arm trial of Sym004 versus each of its component monoclonal antibodies, futuximab and modotuximab, in patients with chemotherapy-refractory metastatic colorectal carcinoma and acquired resistance to anti-EGFR monoclonal antibody therapy	II	Active not recruiting	Acquired resistance to anti-EGFR therapy	Sym004	Futuximab or modotuximab
CHRONOS NCT03227926	A Phase II trial of rechallenge with panitumumab driven by RAS clonal-mediated dynamic of resistance	II	Recruiting	RAS, progression following anti-EGFR therapy	Panitumumab	NA
RASINTRO NCT03259009	Predictive impact of RAS mutations in circulating tumour DNA for efficacy of anti-EGFR reintroduction treatment in patients with metastatic colorectal cancer	NR	Not yet recruiting	RAS, progression following anti-EGFR therapy	Anti-EGFR monoclonal antibody	NA
FIRE-4 NCT02934529	A randomised study to assess the efficacy of cetuximab rechallenge in patients with metastatic colorectal cancer (RAS wild-type) responding to first-line treatment with FOLFIRI plus cetuximab	III	Recruiting	RAS, progression following FOLFIRI + cetuximab	Cetuximab	Anti-EGFR-free treatment (investigator’s choice)
A-REPEAT NCT03311750	Single-arm Phase II study of panitumumab rechallenge in combination with oxaliplatin- or irinotecan-based chemotherapy in patients with RAS wild-type advanced colorectal cancer	II	Recruiting	RAS, progression following anti-EGFR therapy	Panitumumab	NA

BRAF B-rapidly accelerated fibrosarcoma, dMMR deficient mismatch repair, EGFR epidermal growth factor receptor, ERCC1 excision repair cross-complementation group 1, FOLFIRI leucovorin, fluorouracil, and irinotecan, FOLFOX leucovorin, fluorouracil, and oxaliplatin, HER2 human epidermal growth factor 2, mCRC metastatic colorectal cancer, MSI microsatellite instability, MSI-H microsatellite instability high, NA not applicable, NR not reported, PD-L1 programmed cell death ligand 1, PIK3CA phosphatidylinositol 3-kinase catalytic subunit alpha, RAS rat sarcoma