Background: Tebe is a T-cell receptor bispecific (gp100 x CD3) against gp100 peptide-HLA-A2 complexes that are overexpressed in uveal (UM)/cutaneous melanoma (CM). Tebe is the only therapy to show an OS benefit (HR 0.51) in a phase (Ph) 3 trial in previously untreated metastatic UM. In a prior Ph 1 trial, tebe demonstrated monotherapy activity in anti-PD1 naïve mCM (1-yr OS, approx. 74%). The safety and initial activity of tebe with dose escalation of durva and/or treme in previously treated mCM has been reported. Here, we present updated OS in the subset of mCM patients (pts) relapsed or refractory to prior anti-PD1, a population where recent reports suggest a benchmark 1-yr OS of approximately 55% and median OS of approximately 14 months (mos). Methods: Patients with HLA-A2+, pre-treated mCM received weekly tebe (IV) monotherapy in Arm 4a or in combination with dose escalation of durva and/or treme (IV) on day 15 of each cycle (Arms 1-3). Primary objective was RP2D, secondary objectives were safety and efficacy. Subgroup analyses were performed for durva doses ≥10 mg/kg, a threshold previously defined by Bavarel et al, 2018. Analysis performed on data cut-off 04 January 2022 with median follow up for 14.3 mos. [NCT02535078] Results: 112 pts were treated with median age 59, 23% were ECOG = 1, 37% were BRAFm (73% received prior BRAFi/MEKi), 55% had LDH > ULN. 92% of pts were 2L+ and 74% 3L+; median 3 prior lines. The safety profile of all therapy arms within this study therapy remains very favorable with no new safety signals identified. 97 of 112 pts were documented as relapsed or refractory to prior anti-PD1 (80% also received ipilimumab). Of these 97 pts, 32 received tebe + durva (Arm 1), 13 received tebe + treme (Arm 2), 26 received triplet therapy (Arm 3), and 20 received tebe monotherapy (Arm 4a). 33 of 97 pts in any arm received durva ≥ 10 mg/kg with 1-yr OS of 79%, 2-yr OS of 34%, and median OS of 20 mos. 64 of 97 pts received durva < 10 mg/kg with 1-yr OS of 53%, 2-yr OS of 24%, and median OS of 13 mos. Tebe + durva doublet therapy had similar OS to triplet therapy with tebe + durva + treme: 1-yr OS of 74% vs. 76%, and 2-yr OS of 32% vs. 27%, respectively. Conclusions: Promising OS is seen in mCM similar to mUM, with both tumor types overexpressing gp100. In mCM relapsed or refractory to prior anti-PD1, tebe with anti–PD-L1 continues to demonstrate promising OS (1-yr, approx. 75%) compared to recent benchmarks (1-yr, approx. 55%). These data provide rationale for a randomized study of tebe with anti-PD(L)1 in mCM. Clinical trial information: NCT02535078.