Abstract CT038: Kinetics of radiographic response for tebentafusp (tebe) in previously treated metastatic uveal melanoma (mUM) patients (pts) achieving prolonged survival
Authors: Butler Marcus O. , Sato Takami , Carvajal Richard D. , Sacco Joseph J. , Abdullah Shaad E. , Holland Chris , Goodall Howard , Shoushtari Alexander N. 
Published: July 2021

Background: The phase 3 IMCgp100-202 trial (NCT03070392) (Study 202) in untreated mUM demonstrated improved overall survival (OS), HR=0.51, at the first pre-specified interim analysis. This OS benefit and the promising estimated 12-month OS rate of 62% observed in previously treated mUM pts on the phase 2 IMCgp100-102 trial (Study 102; NCT02570308) is not explained by RECIST responses alone. In this post hoc analysis of Study 102, we describe the tumor kinetics of pts with prolonged survival (OS ≥ 12 mo).

Methods: 127 pts with 2L+ mUM received single agent tebe during the expansion phase of Study 102, where treatment beyond RECIST progression was permitted. Analyses of baseline (BL) and on-treatment tumor measurements, best response and time to progression used in this analysis were adjudicated by an independent radiologic committee.

Results: With 19.5 mo median follow-up, 59% (75/127) of pts had OS ≥ 12 mo. Of these 75, a minority had RECIST partial response (PR: 8%; 6/75) and the rest had a best response of stable disease (SD: 57%; 43/75), progressive disease (PD: 33%; 25/75), or not evaluable (NE: 1%; 1/75). In contrast, among 41% (52/127) of pts with OS &lt; 12 mo, 27% (14/52) had SD, 67% (35/52) had PD, and 6% were NE (3/52) as best response. Pts with OS ≥ 12 mo were more likely to have a largest liver metastasis of &lt; 3 cm (43% vs 23%). There were no major differences in the use of prior immunotherapy between the two OS groups.

Most pts with OS ≥ 12 mo (59%; 44/75) had at least some reduction in the sum of target lesions, regardless of RECIST response. The majority of these 44 pts (64%; 28/44) had durable tumor reduction defined by PFS &gt; 6 mo. In contrast, among OS &lt; 12 mo pts, reduction in the sum of target lesions was infrequent (13%; 7/52), and none were durable.

Most pts with tumor growth as best change in target lesions had OS &lt;12 mo (58%; 38/65) compared to OS ≥ 12 mo (42%; 27/65). Among pts with tumor growth, the median BL tumor burden was lower and the rate of increase over time was slower for pts with OS ≥ 12 mo (BL: 59 mm, W8: 68 mm, W16: 68 mm) compared to pts with OS &lt; 12 mo (BL: 113 mm, W8: 129 mm, W16: 143 mm).

Interestingly, 42% (25/60) of pts with best response of PD had OS ≥ 12 mo including 4 pts with evidence of tumor shrinkage at 6 months or later. The reason for PD (new lesions or growth in index lesions) was comparable between both OS groups. More pts continued treatment beyond progression in the OS ≥ 12 (81%) compared to OS &lt; 12 mo (56%).

Conclusion: Analysis of tumor kinetics while on tebe, the first TCR bispecific to report an OS benefit in a solid tumor, suggests most pts with OS ≥ 12 mo are best described by a new type of immune-related response characterized by durable tumor reduction and slowing rate of tumor growth. RECIST responses therefore capture a minority of patients with OS ≥ 12 mo, while just under half of pts with RECIST PD still had promising OS.

Citation Format: Marcus O. Butler, Takami Sato, Richard D. Carvajal, Joseph J. Sacco, Shaad E. Abdullah, Chris Holland, Howard Goodall, Alexander N. Shoushtari. Kinetics of radiographic response for tebentafusp (tebe) in previously treated metastatic uveal melanoma (mUM) patients (pts) achieving prolonged survival [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr CT038.