884TiP A phase Ib/II multicenter, randomized, umbrella study evaluating novel treatment combinations in melanoma (MORPHEUS-MELANOMA)

Immune checkpoint inhibitors (ICIs) targeting cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) and programmed cell death 1 (PD-1) have improved overall survival (OS) in patients (pts) with advanced melanoma, neoadjuvant ICIs can induce tumor regression pts resectable melanoma. Targeting other co-inhibitory receptors, such as lymphocyte activation gene-3 (LAG-3) or immunoglobulin ITIM domain (TIGIT), combining agents multiple immune evasion mechanisms may enhance antitumor activity. MORPHEUS-MELANOMA (NCT05116202) is a phase 1b/2 multicenter, randomized, open-label, umbrella study treatment-naive, stage III (Cohort 1) previously treated IV 2) Cohort will be randomized to receive 6 weeks of treatment 3 experimental arms (RO7247669 [bispecific anti–PD-1/anti–LAG-3], atezolizumab [anti–PD-L1] + tiragolumab [anti–TIGIT], RO7247669 tiragolumab) comparator arm (nivolumab mg/kg [anti–PD-1] ipilimumab [anti–CTLA-4]). Pts stratified by region (Australia vs Rest World) lactate dehydrogenase (≤ > ULN). 2 until unacceptable toxicity loss clinical benefit; new added treatments become available. The enroll ∼61-191 pts, including ≥ safety run-in 2. Experimental preliminary (20 per arm) an expansion additional arm). Primary end point for pathologic response rate at surgery independent review; secondary points are local assessment, event-free survival, recurrence-free OS, objective (ORR), safety. ORR investigator assessment; progression-free duration response, disease control rate, Biopsies collected baseline, cycle (both cohorts), 1). currently enrolling, 21 sites planned Australia, Europe, USA. NCT05116202. Editorial assistance was provided Melanie Sweetlove, MSc (ApotheCom, San Francisco, CA, USA), funded F. Hoffmann-La Roche Ltd.