Clinical Commentary: Tawbi Assesses Toxicities of Therapies in Advanced Melanoma
Source: Targeted Oncology, April 2023
We have randomized phase 3 data for pembrolizumab [Keytruda], nivolumab, and…nivolumab plus ipilimumab [Yervoy], so I completely agree that all of these [agents are considered] category 1 treatments by the NCCN [National Comprehensive Cancer Network] because all have shown improvements over single-agent ipilimumab. That is kind of where the category 1 comes from when including overall survival [OS] benefit. I consider NCCN guidelines to be…very safe.… They don’t include options just because they exist.
However, [combination] pembrolizumab and low-dose ipilimumab has been tried in 1 large single-arm study called KEYNOTE-29 [NCT02089685] and [found to be]…safer than the combination of ipilimumab and nivolumab or high-dose ipilumumab. Yet, most of…[the] relevant data are from a second-line study that showed about a 25% response rate in the second line low dose of ipilimumab or pembrolizumab. So, personally, I don’t necessarily agree with this recommendation as a first-line regimen for low-dose ipilimumab/ pembrolizumab, but obviously this is up for discussion.
Relatlimab’s Role
Relatlimab is a novel antibody that blocks LAG3…. It’s one of those interesting receptors and is quite different than PD-1. It’s expressed on activated T cells and exhausted T cells. Initially, people were thinking that it has an association with MHC class II, the primary ligand, but more and more data are arising to show that it’s directly associated with the TCR CD3, basically signaling cascade. It actually modulates TCR signaling, so it makes a bigger impact in a place where there’s a lot more TCR signaling happening, and that’s probably why it works better in the first line than… in the second line.