Background: Treatment of patients with BRAF V600–mutant melanoma includes BRAF/MEK-inhibitor combinations based on demonstrated benefits on progression-free survival (PFS) and overall survival (OS). To better understand the proportion of patients who derive long-lived benefit and their characteristics, we performed an updated analysis of OS and other endpoints from the COLUMBUS trial. Methods: In Part 1 of COLUMBUS, […]

Background: We conducted the phase 3 double-blind EORTC 1325/KEYNOTE-054 trial to evaluate pembrolizumab vs placebo in patients (pts) with resected high-risk stage III melanoma. Based on 351 recurrence-free survival (RFS) events and at a median follow-up of 1.25 years (yrs), pembrolizumab improved RFS (hazard ratio (HR) 0.57, P<0.0001) as compared to placebo (Eggermont, NEJM 2018). […]

Background: Previous results of the COMBI-AD trial (NCT01682083) showed a significant relapse-free survival (RFS) benefit with 12 mo of adjuvant D+T vs placebo (PBO) in pts with high-risk resected stage III BRAF V600E/K–mutant melanoma. In the primary analysis, 3-year RFS rates with D+T vs PBO were 58% vs 39% (hazard ratio [HR], 0.47 [95% CI, 0.39-0.58]; P< .001). […]

Background OpACIN-neo tested 3 dosing schemes of neoadjuvant (neoadj) IPI+NIVO and identified 2 cycles of IPI 1mg/kg + NIVO 3mg/kg (I1N3) as the most favorable with a pathologic (path) response rate (pRR) of 77% and 20% grade 3-4 irAEs. After 17.6 months median FU, 1/64 (2%) patients (pts) with path response vs 13/21 (62%) of […]

Background: LOGIC2 evaluates the benefit of a 3rd agent added to encorafenib (enco)/binimetinib (bini), selected at progression based on the genetic tumor evolution. Methods: In part I/run-In, pts were treated with enco/bini until disease progression (as defined per RECIST v1.1). Foundation One NGS was applied on a baseline sample and on a PD sample. Based […]

Background: PD1 induces long-term responses in approximately 30% of MM pts, however 2/3 are resistant (innate or acquired) and will require further treatment. A subset of these pts will benefit from IPI or IPI+PD1, but these pts are yet to be identified. We sought to determine; i) response rate (RR) and survival to IPI+/-PD1 after […]

Background: 5-year follow-up of the phase 3 KEYNOTE-006 study (NCT01866319) showed pembro improved OS vs ipilimumab (ipi) in patients (pts) with advanced melanoma. 3-y OS rate from pembro completion for pts who completed 2 y of pembro was 93.8%. Results with 8 mo of additional follow-up are presented to inform clinical care. Methods: Eligible pts […]

Background: Continuous combination of MAPK inhibition (MAPKi) and anti-PD-(L)1 has been investigated by several trials to improve outcome of BRAFV600 mutated melanoma patients. A major obstacle for continuous combination is the high frequency (~60%) of grade 3-4 treatment-related adverse events (TRAE) for which many patients need to discontinue (~40%). In a preclinical model we showed […]

Background: Patients with advanced melanoma who progress on 1st line TT and 2nd line IT have limited treatment options. We explored the safety and efficacy of re-treatment with 3rd line TT. Methods: was pooled from 6 centers in Australia from 2009-2018. Eligible patients with BRAF V600 mutant melanoma had 1st line therapy with a BRAF/MEK inhibitor, 2nd line IO and […]

Background: Early results of the OpACIN-neo study testing 3 different dosing schedules of neoadjuvant IPI + NIVO demonstrated that 2 cycles IPI 1mg/kg + NIVO 3mg/kg (IPI1NIVO3, arm B) was the most favorable schedule with 20% grade 3-4 immunotherapy-related adverse events (irAEs) and a pathologic response rate (pRR) of 77%. After a median follow-up (FU) […]