Early ctDNA reduction in metastatic uveal melanoma correlates better with OS than RECIST response

An early reduction in circulating tumour (ct)DNA after second-line tebentafusp treatment in patients with metastatic uveal melanoma is associated with overall survival (OS), regardless of RECIST response, results from the IMCgp100-202 trial showed.

Treatment with tebentafusp, a novel bispecific fusion protein that targets gp100 and activates T cells, has been shown to reduces the risk of death from metastatic uveal melanoma at 14 months by half, compared with available treatments [1]. However, OS was improved in patients regardless of RECIST best response, suggesting better surrogate efficacy endpoints are needed.

In the IMCgp100-202 trial (NCT02570308), 127 patients with metastatic uveal melanoma were treated weekly with tebentafusp in second line. RECIST was assessed and serum samples (n=118) collected at baseline, week 5, and week 9 were analysed for ctDNA. Dr Alexander Shoushtari (Memorial Sloan Kettering Cancer Center, NY, USA) presented the results [2].

Levels of ctDNA were associated with tumour burden at baseline. At 9 weeks, ctDNA was reduced in 70% of patients on tebentafusp, despite a RECIST response rate of only <10%. ctDNA reduction was strongly associated with improved OS, even in patients with RECIST progressive disease or stable disease. OS rate at 1 year was 100% for patients with ctDNA clearance (n=14) versus 57% for patients with ctDNA not cleared. Best overall response among those with ctDNA clearance was progressive disease in 4 (29%), stable disease in 8 (57%), and partial response in 1 (7%); 1 patient was not evaluable.

Dr Shoushtari concluded that “early ctDNA reduction may be a better surrogate of tebentafusp efficacy than RECIST objective response in patients with metastatic uveal melanoma.”

1. Piperno-Neumann S, et al. Cancer Res 2021; 81 (Suppl), CT002.
2. Shoushtari AN, et al. Early reduction in ctDNA, regardless of best RECIST response, is associated with overall survival (OS) on tebentafusp in previously treated metastatic uveal melanoma (mUM) patients. Abstract 1757O, ESMO Congress 2021, 16–21 September.

 

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Posted on 19 November 202131 January 2024