Table 2.
Ongoing clinical trials investigating the efficacy of a combination of MAPK-directed targeted therapy and CPI therapy
| National Clinical Trial (NCT) Number | Title | Status | Conditions | Interventions | Clinical Phase | Start Date |
|---|---|---|---|---|---|---|
| A BRAF-mutant melanoma: concomitant administration of MAPKdirected and CPI therapy | ||||||
| NCT 04657991 | Randomized, double-blind study of ENC and BIN plus PEM versus placebo plus PEM | Recruiting | Unresectable or metastatic BRAFV600-mutant melanoma | ENC 450 mg + BIN 45 mg + PEM 200 mg vs. PEM 200 mg only | 3 | 12/2020 |
|
(SWOG S2000) |
Randomized trial of ENC plus BIN plus NIVO vs. IPI plus NIVO in BRAFV600-mutant melanoma with MBM | Recruiting | Metastatic cutaneous melanoma with MBM | ENC 450 mg + BIN 45 mg + NIVO 3 mg/kg vs. IPI 3 mg/kg + NIVO 1 mg/kg | 2 | 12/2020 |
| NCT 04657991 | Randomized, double-blind study of ENC and BIN plus PEM versus placebo plus PEM | Recruiting | Metastatic or unresectable locally advanced BRAFV600E/K-mutant- melanoma | ENC 450 mg + BIN 45 mg + PEM 200 mg vs. PEM 200 mg only | 3 | 01/2021 |
| B BRAF-mutant melanoma: sequential administration of MAPK-directed and CPI therapy | ||||||
| NCT 03235245 | MAPK-targeted therapy followed by CPI (IPI and NIVO) vs. IPI plus NIVO (EORTC randomized study (EBIN) | Recruiting |
Unresectable, BRAFV600-mutant stage III melanoma and BRAFV600-mutant stage IV melanoma |
ENC 450 mg + BIN 45 mg for 12 weeks, followed by IPI 1 mg/kg + NIVO 3 mg/kg vs. IPI 1 mg/kg + NIVO 3 mg/kg only | 2 | 10/2018 |
|
(IMPemBra) |
Comparison of PEM with intermittent/short-term dual MAPK inhibition plus PEM | Recruiting | BRAFV600-mutant stage IV melanoma | PEM 200 mg vs. short-term DAB 150 mg + TRA 2 mg + PEM 200 mg vs. intermediate DAB + TRA + PEM vs. long-scheme DAB + TRA + PEM | 2 | 12/2015 |
| NCT 04655157 | A Multi-center phase I/II open label study to evaluate safety and efficacy in participants with ENC alone and with BIN in combination with NIVO and low-dose IPI. (QUAD 01: quadruple melanoma therapy) | Recruiting | Unresectable or metastatic BRAFV600-mutant melanoma high-risk patients | ENC 300 mg + IPI 1 mg/kg + NIVO 3 mg/kg vs. ENC 450 mg + BIN 45 mg + IPI 1 mg/kg + NIVO 3 mg/kg | 1/2 | 02/2021 |
| C BRAF-wild-type: sequential or concomitant administration of MAPK-directed and CPI therapy | ||||||
| NCT 03149029 | Abbreviated MAPK-targeted therapy plus PEM | Active | Unresectable or metastatic melanoma | PEM + DAB + TRA (BRAFV600-mutant) vs. PEM + TRA (BRAF wild-type) | 2 | 11/2017 |
| D Administration of MAPK-directed and CPI therapy in a neoadjuvant setting | ||||||
| NCT 03554083 | Neoadjuvant therapy: A pilot clinical trial | Recruiting | High-risk stage III BRAFV600-mutant melanoma | VEM + COB + ATE for up to 3 months followed by surgery and ATE for up to 8 cycles vs. COB + ATE for up to 3 months followed by surgery and ATE for up to 8 cycles | 2 | 06/2018 |
| NCT 02858921 | Phase II, randomised, open label study of neoadjuvant DAB, TRA w/o and with PEM (NeoTrio) | Recruiting | BRAFV600-mutant resectable stage IIIB/C melanoma | DAB 150 mg + TRA 2 mg (1 we) plus consecutive PEM 2mg/kg for 6 we followed by surgery and PEM 2 mg/kg for 46 we vs. concurrent DAB 150 mg + TRA 2 mg + PEM 200 mg for 6 we followed by surgery and PEM 200mg for 46 we vs. PEM 200 mg only with surgery at week 6 | 2 | 11/2017 |
| NCT 04722575 | NEOadjuvant Plus Adjuvant Therapy with VEM, COB, and ATE applied in combination or sequentually | Recruiting | High-risk resectable melanoma (stage III B-D and oligometastatic stage IV), both BRAF wild-type and BRAFV600-mutant | VEM 960 mg + COB 60 mg followed by surgery and ATE 1200 mg vs. VEM 720 mg + COB 60 mg for 6 we and 2 cycles of ATE 840 mg followed by surgery and ATE 1200 mg vs. COB 60 mg + ATE 840 mg for 6 we followed by surgery and ATE 1200 mg | 2 | 12/2020 |
Abbreviations: ATE = atezolizumab; ALT = alanine-aminotransferase; AST = aspartate aminotransferase; BIN = binimetinib; COB = cobimetinib; CR = complete response; DAB = dabrafenib; DOR = duration of response; DLT = dose-limiting toxicity; DUR = durvalumab; ENC = encorafenib;; HR = hazard ratio; IPI = ipilimumab; NA = not available; NIVO = nivolumab; NR = not reached; ns = not significant; ORR = overall response rate; OS = overall survival; PD = progressive disease; PEM = pembrolizumab; PFS = progression-free survival; (tr)AE = (treatment-related) adverse events; TRA = trametinib; we = week; VEM = vemurafenib