Abstract 831P
Background
Metastatic uveal melanoma (MUM) is a nearly universal fatal disease with limited treatment options. Tebentafusp, a novel bispecific immune mobilizing T cell receptor, provides an overall survival (OS) benefit for MUM in HLA-A*02:01 positive patients despite a low overall response rate (ORR). Immune checkpoint inhibitors (ICI) in first line therapy also have a low ORR but improved survival. Little is known about the outcomes of patients who receive sequential ICI and tebentafusp.
Methods
In this single center retrospective cohort study, we included patients with MUM treated with tebentafusp and ICI (anti PD1 +/- anti CTLA-4) between 2016-2021. Investigator-assessed ICI response rates (RR), progression free survival (PFS) and OS were analyzed and compared when used before or after tebentafusp. X2, Fisher’s exact and Mann-Whitney U tests were used to compare groups and Cox proportional hazards models were fitted. The Log-rank test was used to assess PFS and OS.
Results
Twenty patients were identified: 10 patients who received ICI following tebentafusp (T-I) and 10 patients treated with ICI prior to tebentafusp (I-T). Disease characteristics were similar amongst both groups (Table). Response rates for the T-I group were: partial response (PR): 10% (1), stable disease (SD): 30% (3) and progressive disease (PD): 60% (6). For the I-T group the corresponding rates were: SD: 20% (2) and PD: 80% (8), p = 0.63 between groups. Median PFS from ICI initiation was 2.86 months (95%CI 2.37-NA) for T-I and 2.35 months (95% CI 0.92-NA) for I-T, (p=0.046). Median OS from start of first treatment was 21.47 months (95% CI 15.78-NA) for T-I, and 16.88 months (95% CI 8.52-NA) for I-T (p=0.38). Table: 831P
| Covariate | ICI - Teb (n=10) | Teb - ICI (n=10) | p-value |
| Age | 0.82 | ||
| Median | 60 (51 - 64) | 57 (50 - 66) | |
| Sex | 1 | ||
| Female | 4 (40) | 5 (50) | |
| Male | 6 (60) | 5 (50) | |
| IV Stage | 0.44 | ||
| M1a | 8 (80) | 5 (50) | |
| M1b | 1 (10) | 3 (30) | |
| M1c | 1 (10) | 2 (20) | |
| ECOG | 1 | ||
| 0 | 8 (80) | 7 (70) | |
| 1 | 2 (20) | 3 (30) | |
| Extra Liver Mets | 1 | ||
| No | 3 (30) | 3 (30) | |
| Yes | 7 (70) | 7 (70) | |
| Increased LDH | 0.63 | ||
| No | 8 (80) | 6 (60) | |
| Yes | 2 (20) | 4 (40) |
Conclusions
In this small series, PD- 1 +/- CTLA-4 blocking antibodies may show better clinical efficacy in patients with MUM when administered after tebentafusp rather than before. A larger study is needed to confirm these data. Erica Koch Hein and Diana Paola Arteaga Ceballos contributed equally to this study.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
E.C. Koch: Financial Interests, Personal, Invited Speaker: Novartis, MSD; Financial Interests, Personal, Advisory Board: Novartis, MSD; Financial Interests, Institutional, Other, Funding: Alamos Gold Inc.; Financial Interests, Institutional, Research Grant: Novartis. M. Vilbert: Other, Institutional, Funding: Alamos Gold Inc. T. Pimentel Muniz: Financial Interests, Personal, Research Grant: Novartis; Financial Interests, Institutional, Funding: Alamos Gold Inc. S. Saibil: Financial Interests, Personal, Advisory Board: Novartis. A. Spreafico: Financial Interests, Personal, Advisory Board: Merck, Bristol Myers Squibb, Oncorus, Janssen, Medison & Immunocore; Financial Interests, Institutional, Research Grant: Novartis, Bristol Myers Squibb, Merck, Bayer, Surface Oncology, Northern Biologics, Janssen Oncology/Johnson & Johnson, Roche, Regeneron, Alkermes, Array Biopharma/Pfizer, GSK, Oncorus, Treadwell, Amgen. M.O. Butler: Financial Interests, Personal, Advisory Board: Bristol Myers Squibb, EMD Serono, GlaxoSmithKline, Immunocore, Merck, Novartis, Pfizer, Sanofi; Financial Interests, Institutional, Research Grant: Merck; Financial Interests, Personal, Other, Safety Review Board: Adaptimmune, GlaxoSmithKline. All other authors have declared no conflicts of interest.