1130P - Tebentafusp (tebe) in an ongoing cohort of 72 French patients (pts) with metastatic uveal melanoma (mUM)

Background

Tebe, a bispecific T-cell engager, showed a benefit in response rate, progression-free survival (PFS) and overall survival (OS) in HLA A*02-01^pos mUM pts in the IMCgp100-202 phase III trial. Prior to approval, French Health Authorities allowed an early access to Tebe in May 2021 to mUM pts. We report here our real-world experience with Tebe and analyses of potential prognostic and predictive biomarkers.

Methods

Ongoing ambispective cohort of mUM pts treated with Tebe. Tumor sizes were evaluated according to RECIST 1.1. Circulating tumor DNA (ctDNA) analyses were performed on this cohort and on the 18 pts enrolled in the IMCgp100-202 trial and randomized to Tebe, at Institut Curie. ctDNA was measured by digital droplet PCR (ddPCR) targeting codons 183 & 209 of both GNAQ and GNA11.

Results

72 pts were included from May 26^th 2021 to December 12^th 2022. With a median follow-up of 48 weeks, patients received a median of 22 weeks of Tebe. Out of 60 assessable pts, 33 (55%) showed stable disease and 5 (8%) partial response according to RECIST 1.1. Median PFS (mPFS) was 28 weeks (confidence interval 95% [CI₉₅]: 8-56). OS at 12 months (OS_12m) was 72%. No new, unexpected safety event occurred. Elevated baseline LDH was correlated with poorer OS (Spearman rho= -0.26, p<0.01). 63 pts had mUM carrying somatic mutations detectable by ddPCR (ie GNAQ/GNA11 mutations). Of these, 39 pts (62%) had detectable ctDNA at baseline. Pts with detectable ctDNA at baseline had poorer PFS (mPFS 4.0 vs 14.0 months; HR=2.83, CI₉₅[1.48-5.41]) and OS (OS_12m of 51.5% vs 95.4%; HR=6.11, CI₉₅[2.04-18.3]) than those with undetectable ctDNA. 22 pts cleared their ctDNA at first assessment (12 weeks) and had numerically better OS_12m than those who did not (70% vs 60%; HR = 1.83 CI₉₅[0.92-13.9]).

Conclusions

In this real-world cohort of mUM pts, Tebe is associated with clinical outcomes in lin withthe IMCgp100-202 trial. Baseline ctDNA and LDH are prognostic factors while ctDNA clearance might predict benefit from Tebe. Other analyses are ongoing to identify new predictive biomarkers.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

INSERM.

Disclosure

M. Saint-Ghislain: Financial Interests, Invited Speaker: Oncotream. J. Thery: Financial Interests, Invited Speaker: PharmaMar; Financial Interests, Advisory Board: Pfizer, AstraZeneca. P. Combe: Financial Interests, Invited Speaker: Eisai, BMS GmbH&Co.KG, Novartis, Clovis Oncology, AstraZeneca. C. Dutriaux: Financial Interests, Advisory Board: Bristol Myers Squibb, MSD, Pierre Fabre. S. Piperno-Neumann: Financial Interests, Personal, Advisory Board: Immunocore, Pierre Fabre, Atlanthera. M.J. Rodrigues: Financial Interests, Personal, Invited Speaker: Immunocore; Financial Interests, Personal, Advisory Board: GSK, AstraZeneca; Financial Interests, Institutional, Coordinating PI: Johnson & Johnson; Non-Financial Interests, Institutional, Product Samples: MSD. All other authors have declared no conflicts of interest.