Findings

First-line: checkpoint inhibition

Relatlimab is an antibody against LAG3 – an immune checkpoint found on T cells and co-expressed with PD-1 on tumour-infiltrating lymphocytes.¹
LAG3 expression has been shown to be associated with therapeutic resistance to anti-PD-1.
LAG3 and PD-1 inhibition may be complementary, overcoming resistance to anti-PD-1 alone.
Data from the RELATIVITY trial show superior progression-free survival for relatlimab plus nivolumab compared to nivolumab alone, regardless of prespecified subgroups and stratification factors, and with no new safety signals.²

New drugs for these patients include lenvatinib and lifileucel.
Levantinib may help to shift the tumour microenvironment to an immune stimulatory state via dual VEGF and FGFR inhibition.^3,4
In the Phase 2 LEAP-004 trial, patients receiving lenvatinib plus pembrolizumab had an objective response rate of 21.4%, but with median duration of response of only 8.3 months.⁵
Phase 3 and neoadjuvant trials for lenvatinib are ongoing.
Lifileucel is an adoptive cell therapy using autologous tumour infiltrating lymphocytes (TIL).
In the C144-01 trial there was an objective response rate of 36.4%, and the median duration of response has not yet been reached.⁶

Tebentafusp is a bispecific molecule with two domains.
Uveal melanoma trials in first- and second-line patients show promising results in this notoriously difficult-to-treat disease.
For cutaneous melanoma, results of larger cohorts are pending.
Despite low response rates and the fast tumour progression, tebentafusp patients appear to have statistically and clinically improved overall survival.