Background: Tebentafusp (gp100 x CD3) has demonstrated an overall survival (OS) benefit in mUM. Benefit was observed in patients (pts) who achieved a RECIST v1.1 partial response (PR), stable disease (SD) and even progressive disease (PD) (Nathan 2021). In Phase (Ph) 1, some melanoma pts had SD with tumor reduction > 10% that was confirmed at ≥ 1 subsequent scan (referred to as minor response, MR). In Ph 2, an analysis of MR was pre-specified as an endpoint and presented here. Methods: 127 HLA-A*02:01+ pts with previously treated mUM received weekly intravenous tebentafusp following intra-pt dose escalation of 20mcg Week 1, 30mcg Week 2 and 68mcg Week 3+ (NCT02570308; Carvajal 2022). Radiologic assessments were performed every 8 weeks until week 40, then q12 weeks. Tumor assessment was evaluated by a blinded independent review committee per RECISTv1.1. MR was prospectively defined as RECISTv1.1 best response of SD with reduction in sum of target lesions of -10% to -29% and which was confirmed ≥ 4 weeks later. ctDNA levels were assessed using a targeted mPCR-NGS assay for mutations in 15 genes including mUM oncogenes GNAQ, GNA11, SF3B1, CYSLTR2, PLCB4 and EIF1AX (Natera). Molecular response was defined as ≥ 0.5 log [68%] ctDNA reduction by week 9. Data cut off: Oct 2022. Median duration of follow-up was 46 months. Results: Of 127 pts, the clinical benefit rate of PR + SD was 50% (64/127). 25% (32/127) had any tumor reduction that was confirmed on ≥ 1 subsequent scan, including 6 PR (ORR 5%) and 26 SD (20%). 8/26 SD (6% of 127) met the pre-defined threshold for MR, most (5/8) had >20% reduction. The median duration of response for PR and MR were 8.7 months and 10.6 months, respectively. The estimated percent of pts with PR and MR remaining in response at Month 20 were 20% and 33%, respectively. 3/6 PR pts were alive ≥ 3 years vs 3/8. 58% of PR + SD pts with evaluable ctDNA had a molecular response (26/45), including 2/4 PRs and 5/5 MRs. Conclusions: This Ph2 UM study prospectively confirmed that a subset of SD patients had tumor reduction over multiple scans. The frequency of minor response was similar to that of PR and had similar durability, OS and ctDNA molecular response. SD with confirmed tumor reduction is an emerging endpoint for the ImmTAC platform and will be studied in other trials (NCT05549297, NCT04262466). Clinical trial information: NCT02570308.