Comparison of clinical outcomes of stable disease with confirmed tumor reduction and RECIST partial response for tebentafusp in metastatic uveal melanoma (mUM).

person Alexandra Ikeguchi Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX info_outline Alexandra Ikeguchi, Takami Sato, Marcus O. Butler, Richard D. Carvajal, Joseph J Sacco, Alexander Noor Shoushtari, Jessica Cecile Hassel, Paul D. Nathan, Josep M. Piulats, Douglas Buckner Johnson, Jason J. Luke, Enrique Espinosa, Serge Leyvraz, Laura Collins, Ramakrishna Edukulla, Piruntha Thiyagarajah, Omid Hamid

Authors person Alexandra Ikeguchi Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX info_outline Alexandra Ikeguchi, Takami Sato, Marcus O. Butler, Richard D. Carvajal, Joseph J Sacco, Alexander Noor Shoushtari, Jessica Cecile Hassel, Paul D. Nathan, Josep M. Piulats, Douglas Buckner Johnson, Jason J. Luke, Enrique Espinosa, Serge Leyvraz, Laura Collins, Ramakrishna Edukulla, Piruntha Thiyagarajah, Omid Hamid Organizations Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, Jefferson Medical College, Philadelphia, PA, Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University of Toronto, Toronto, ON, Canada, Columbia University Medical Center, New York, NY, The Clatterbridge Cancer Centre and University of Liverpool, Liverpool, United Kingdom, Memorial Sloan Kettering Cancer Center, New York, NY, University Hospital Heidelberg, Heidelberg, Germany, Mount Vernon Cancer Centre, Noorthwood, United Kingdom, Institut Català d’Oncologia–Bellvitge Institute for Biomedical Research, Barcelona, Spain, Vanderbilt University Medical Center, Nashville, TN, UPMC Hillman Cancer Center, Pittsburgh, PA, Medical Oncology Department. Hospital Universitario La Paz - CIBERONC, Madrid, Spain, Charité– Universitätsmedizin Berlin, Berlin, Germany, Immunocore Ltd., Abingdon, United Kingdom, Immunocore LLC, Rockville, MD, Immunocore Ltd., Abindgon, United Kingdom, The Angeles Clinic and Research Institute, a Cedars-Sinai Affiliate, Los Angeles, CA Abstract Disclosures Research Funding Immunocore 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.

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