Table 1.

Selected Clinical Trials using BRAFi and/or MEKi in adjuvant and neoadjuvant applications for CM.

Studies with Reported Outcomes
Trial, NCT Number	Patient Population		Treatment Schedule	Study Design		Outcomes	Reference
COMBI-AD, NCT01682083	Resected stage III, BRAF V600 mutant CM		12-months adjuvant dabrafenib + trametinib vs. double placebo	Randomized, double-blind, placebo-controlled phase III		Median relapse-free survival at 60 months median follow-up: not reached vs. 16.6 months 5-year relapse-free survival rate: 52% vs. 36%; 5-year distant metastasis-free survival rate: 65% vs. 54%	(Dummer, Hauschild, et al., 2020)
Combi-Neo, NCT02231775	Resectable stage III or oligometastatic stage IV, BRAF V600 mutant CM		8-weeks neoadjuvant dabrafenib + trametinib, followed by surgery and up to 44 weeks of adjuvant dabrafenib + trametinib vs. standard of care adjuvant therapy	Randomized, open-label, phase II		Median event-free survival at 18.6 months median follow-up: 19.7 months vs. 2.9 months; trial stopped early due to significantly improved outcomes in the neoadjuvant arm	(Amaria, Prieto, et al., 2018)
NeoCombi, NCT01972347	Resectable stage IIIB-C, BRAF V600 mutant CM		12-weeks neoadjuvant dabrafenib + trametinib, followed by surgery and 40 weeks of adjuvant dabrafenib + trametinib	Single-arm, open-label, phase II		Median relapse-free survival at 27 months median follow-up: 30.6 months with complete pathological response vs. 18.0 months non-complete pathological response	(Long et al.,2019)
Ongoing Studies
Trial, NCT Number		Patient Population	Treatment Schedule		Study Design	Status
NCT02036086		Unresectable, stage IIIB-C, BRAF V600 mutant CM	8-weeks neoadjuvant vemurafenib + cobimetinib, followed by surgery and adjuvant vemurafenib + cobimetinib		Single-arm, open-label, pilot phase II	Active, not recruiting
NCT04741997		Stage IIIB-D or stage IV, BRAF V600 mutant CM	24-weeks neoadjuvant encorafenib + binimetinib, followed by surgery and adjuvant encorafenib + binimetinib vs. 24-weeks neoadjuvant encorafenib + binimetinib, followed by surgery and adjuvant nivolumab		Randomized, open-label, pilot phase I	Recruiting
NCT04221438		Resectable, stage IIIB-D, BRAF V600 mutant CM	8-weeks neoadjuvant encorafenib + binimetinib followed by surgery and adjuvant encorafenib + binimetinib		Single-arm, open-label, phase II	Not yet recruiting
PREMIUM, NCT05097378		Resectable stage III or oligometastatic stage IV, BRAF V600 mutant CM	8-weeks neoadjuvant encorafenib + binimetinib followed by surgery and up to 44-weeks adjuvant encorafenib + binimetinib vs. surgery and standard of care adjuvant therapy		Randomized, open-label, phase II	Not yet recruiting
Neo Trio, NCT02858921		Resectable stage IIIB-C, BRAF V600 mutant CM	6-weeks neoadjuvant: dabrafenib + trametinib + sequential pembrolizumab vs. dabrafenib + trametinib + concurrent pembrolizumab vs. pembrolizumab alone; all arms followed by surgery and adjuvant pembrolizumab		Randomized, open-label, phase II	Active, not recruiting
NeoACTIVATE, NCT03554083		Resectable stage III CM	12-weeks neoadjuvant atezolizumab + tiroligumab, or atezolizumab + cobimetinib, or atezolizumab + vemurafenib + cobimetinib; all arms followed by surgery and adjuvant atezolizumab		Open-label, pilot phase I	Recruiting
NEO-TIM, NCT04722575		Resectable stage III or oligometastatic stage IV CM	BRAF V600 mutant: 6-weeks neoadjuvant vemurafenib + cobimetinib vs. vemurafenib + cobimetinib + atezolizumab; BRAF wild-type: 6-weeks neoadjuvant cobimetinib + atezolizumab; all arms followed by surgery and adjuvant atezolizumab		Randomized, open-label, phase II trial	Recruiting
ALTER-PATH NeoDT, NCT04310397		Resectable stage IIIB-D, BRAF V600 mutant CM	8-weeks neoadjuvant dabrafenib + trametinib, followed by surgery and adjuvant dabrafenib + trametinib or spartalizumab		Single-arm, open-label, pilot phase II	Active, not recruiting