LBA41 Phase II study SECOMBIT (sequential combo immuno and target therapy study): 4-years OS data and preliminary biomarkers evaluation

To investigate the best sequential strategy in BRAFV600-mutated melanoma, SECOMBIT study was carried out, a three parallel arms phase 2 randomized trial (NCT02631447). We used combination of encorafenib/binimetinib (E+B) as targeted therapy (T-T) and ipilimumab/nivolumab (I+N) immunotherapy (I-O). explored T-T (Arm A) or I-O B) first line with switch at progression, well “sandwich” preplanned switched to combo after 8 weeks, returning back progression C). In our previous report overall survival (OS) total free (tPFS) rates 3 years showed better trend Arm B C. From Nov 2016 May 2019, 251 patients (pts) from 37 centers 9 countries untreated, metastatic BRAFV600 melanoma were enrolled. Pts A, OS is primary endpoint study. Secondary endpoints include tPFS, 4-year rate preliminary biomarkers evaluation. NGS analysis 21 inflammatory cytokines through Luminex assay HS-ELISA evaluated baseline 83 pts (29,24,30 for A,B,C) 93 (28,29, 36 respectively. The 4 years, median follow up 43 months (IQR: 37-51), calculated all pts, subgroups normal elevate LDH level < ≥ sites. tPFS subgroup are shown table 1. we observed correlation JAK mutation survival, IFN-gamma CXCL5 ORR PFS.Table: LBA41Arm A (T-T)Arm (I-O)Arm C (sandwich)4-year tPFS29%55%54%4-year OS46%64%59%4-year <3 ms33%59%59%4-year ms55%65%62%4-year ≥3 ms23%51%46%4-year ms32%63%54%4-year nLDH31%58%51%4-year nLDH53%70%56%3-year eLDH23%48%60%3-year eLDH42%53%65%4-year eLDH18%48%60%4-year eLDH42%53%65%Biomarkers Analysis yearsJAK WT -OS57%53%71%JAK -PFS38%53%53%JAK MUT - OS75%100%65%JAK PFS75%100%61%IFN-g high ORR67%0%56%IFN-g low ORR67%33%74%CXCL5 PFS>2y27%45%40%CXCL5 PFS>2y56%71%63% Open new tab revealed positive on indicating planned could be beneficial treatment strategy. B, IFN Gamma seems related ICI response. mutations associated long term OS. Further evaluations ongoing.