Dr Coupe on the Background of IMM60 With Pembrolizumab in Melanoma or NSCLC

Nicholas Coupe, MBBS, PhD, oncologist, Oxford University Hospitals, NHS Foundation Trust, discusses the rationale for investigating IMM60 with pembrolizumab (Keytruda) in patients with advanced melanoma or metastatic non-small cell lung cancer (NSCLC), as well as key background information that led to this investigation.

At the 2023 ASCO Annual Meeting, investigators presented data from the ongoing, first-in-human, dose-finding, randomized phase 1/2 IMPORT-201 trial (NCT05709821) which is investigating the novel agent IMM60 as both a monotherapy and in combination with the PD-1 inhibitor pembrolizumab.

The invariant natural killer (NK) T-cell agonist IMM60 is a unique therapy, Coupe begins. Invariant NK T cells are cells that have a broad range of activity across the immune system, affecting both the adaptive and innate arms of the immune system, he says. Once activated, invariant NK T cells can directly affect tumors, Coupe notes. Notably, there is some preclinical work showing that NK T cells can directly upregulate PD-L1 expression in tumor cells, Coupe says, explaining that they can also engage favorably with antigen-presenting cells, such as dendritic cells, which can potentially enhance their immunogenic effect against tumor cells.

Additionally, NK T cells can increase the ability of cytotoxic T cells to be recruited to attack tumor cells and can alsoengage with B-cells, potentially affecting the way the antibodies engage with the tumors, Coupe expands. Moreover, research shows that invariant NK T cells play a key role in optimizing the tumor microenvironment, making it a favorable environment for the destruction of tumor cells. Other research with NK T cell agonists has been conducted in the past, and a preceding compound has demonstrated some activity in this setting, Coupe says. However, the pharmacokinetic and pharmacodynamic profiles of IMM60 supersede that activity, and in the future, IMPORT-201 investigators hope to show promising clinical activity with this agent, Coupe concludes.