Extended Data Fig. 1: Study designs for (a) part 1 and (b) part 2 of COMBI-i.

ALT, alanine aminotransferase; AST, aspartate aminotransferase; BID, twice daily; CD, cluster of differentiation; CNS, central nervous system; DCR, disease control rate; DLT, dose-limiting toxicity; DOR, duration of response; ECOG PS, Eastern Cooperative Oncology Group performance status; FFPE, formalin-fixed paraffin-embedded; ORR, overall response rate; OS, overall survival; PD, progressive disease; PD-L1, programmed death ligand 1; PFS, progression-free survival; PK, pharmacokinetics; Q4W, every 4 weeks; Q8W, every 8 weeks; QD, once daily; RECIST, Response Evaluation Criteria in Solid Tumors; RP3R, recommended phase 3 regimen; S, screening; ULN, upper limit of normal.^a BRAF V600 mutation was assessed based on local testing (followed by central confirmation using the bioMérieux THxID-BRAF assay). ^b With systemic therapy including checkpoint inhibitors, targeted therapy, chemotherapy, biologic therapy, tumor vaccine therapy, or investigational treatment for unresectable or metastatic melanoma; prior intralesional, adjuvant, or neoadjuvant therapy was allowed if completed ≥ 6 months prior to start of study treatment, and prior radiation therapy was allowed if completed ≥ 4 weeks prior to start of study treatment. ^c DL-1b: DLT observation period starts on cycle 2, day 1 (C2D1 [day 29]). Patients who did not tolerate dabrafenib and/or trametinib and discontinued during the first 4 weeks were to be replaced due to insufficient exposure.