Table 2.

Selected Clinical Trials using BRAFi/MEKi in combination with ICi for CM.

Concurrent with ICi
Studies with Reported Outcomes
Trial, NCT Number	Patient Population	Treatment Schedule	Study Design	Outcomes	Reference
KEYNOTE-022, NCT02130466	Unresectable stage III or stage IV, BRAF V600 mutant CM	Dabrafenib + trametinib + pembrolizumab vs. dabrafenib + trametinib + placebo	Randomized, double-blind, placebo-controlled phase II	Median PFS survival at 36.6 months median follow-up: 16.9 months vs. 10.7 months	(Ferrucci et al., 2020)
COMBI-i, NCT02967692	Unresectable stage III or stage IV, BRAF V600 mutant CM	Dabrafenib + trametinib + spartalizumab vs. dabrafenib + trametinib + placebo	Randomized, double-blind, placebo-controlled phase III	Median PFS at 27.2 months: 16.2 months vs. 12.0 months; study did not meet its primary endpoint	(Dummer et al., 2022)
NCT02027961	Unresectable stage III or stage IV CM	Cohort A: BRAF V600 mutant CM treated with dabrafenib + trametinib + durvalumab; Cohort B: BRAF wild-type CM treated with trametinib + concurrent durvalumab; Cohort C: BRAF wild-type CM treated with trametinib + sequential durvalumab	Open-label, dose escalation and expansion phase I	Median PFS for Cohort A at 20.8 months median follow-up: 11.2 months; for Cohort B at 22.1 months median follow-up: 4.9 months; Cohort C at 20.8 months median follow-up: 5.9 months	(Ribas et al., 2020)
IMspire150, NCT02908672	Unresectable stage IIIC or stage IV, BRAF V600 mutant CM	Vemurafenib + cobimetinib + atezolizumab vs. vemurafenib + cobimetinib + placebo	Randomized, double-blind, placebo-controlled phase III	Median PFS at 18.9 months median follow-up: 15.1 months vs. 10.6 months	(Gutzmer et al., 2020)
Ongoing Studies
Trial, NCT Number	Patient Population	Treatment Schedule	Study Design	Status
STARBOARD, NCT04657991	Unresectable stage IIIB-D or stage IV, BRAF V600 mutant CM	Encorafenib + binimetinib + pembrolizumab vs. placebo + pembrolizumab	Randomized, double-blind, placebo-controlled phase III	Recruiting
TRIDENT/TRIBECA, NCT02910700	Unresectable stage III or stage IV, BRAF V600 mutant CM	Dabrafenib + trametinib + nivolumab, or trametinib + nivolumab, or encorafenib + binimetinib + nivolumab	Non-randomized, open-label, phase II	Recruiting
Sequential with ICi
Studies with Reported Outcomes
Trial, NCT Number	Patient Population	Treatment Schedule	Study Design	Outcomes	Reference
DREAMSeq, NCT02224781	Unresectable stage III or stage IV, BRAF V600 mutant CM	Ipilimumab + nivolumab followed by crossover to dabrafenib + trametinib vs. dabrafenib + trametinib followed by crossover to ipilimumab + nivolumab	Randomized, open-label, phase III	2-year OS rate: 72% vs. 52%	(Atkinson et al., 2021)
SECOMBIT, NCT02631447	Unresectable stage III or stage IV, BRAF V600 mutant CM; BRAF V600 mutant MM	Ipilimumab + nivolumab followed by crossover to encorafenib + binimetinib vs. encorafenib + binimetinib followed by crossover to ipilimumab + nivolumab vs. 8-weeks induction with encorafenib + binimetinib, then ipilimumab + nivolumab followed by crossover to encorafenib + binimetinib	Randomized, open-label, phase II	2-year OS rate: 73% vs. 65% vs. 69% 2-year PFS rate: 65% vs. 46% vs. 57%	(Ascierto, Mandala, et al., 2021)
Induction before ICi
Ongoing Studies
Trial, NCT Number	Patient Population	Treatment Schedule	Study Design	Status
ImmunoCobiVem, NCT02902029	Unresectable stage IIIB-C or stage IV, BRAF V600 mutant CM	3 months induction with vemurafenib + cobimetinib followed by vemurafenib + cobimetinib and crossover to atezolizumab vs. 3 months induction with vemurafenib + cobimetinib followed by atezolizumab and crossover to vemurafenib + cobimetinib	Randomized, open-label, phase II	Active, not recruiting
EBIN, NCT03235245	Unresectable stage III or stage IV, BRAF V600 mutant CM; BRAF V600 mutant MM	12-weeks induction with encorafenib + binimetinib followed by ipilimumab + nivolumab vs. upfront ipilimumab + nivolumab	Randomized, open-label, phase II	Recruiting
COWBOY, NCT02968303	Unresectable stage III or stage IV, BRAF V600 mutant CM	6-weeks induction with vemurafenib + cobimetinib followed by ipilimumab + nivolumab vs. upfront ipilimumab + nivolumab	Randomized, open-label, phase II	Recruiting