Audio: Thank you, thanks for the question so this study titled IMP is an early phase dose-escalation study first in hand study evaluating effectiveness of a new compound called PORT-2 now PORT-2 is an invariant natural killer…Read Full Transcript Here
Nicholas Coupe, MBBS, Oncologist at Oxford University Hospitals NHS Foundation Trust. In this interview, he speaks about the ASCO 2022 abstract – A phase 1 first-in-human dose-finding/randomized phase 2 study of IMM60 and pembrolizumab (PEM) in advanced melanoma and non"“small cell lung cancer (NSCLC; IMP-MEL).
Origins:
Invariant natural killer T-cells (iNKTs) exhibit characteristics of both innate cells (NK-like) and T-cells (can prime and boost an adaptive immune response). The importance of this relatively rare lymphocyte subset has increased due to its dual potential to have a direct cytotoxic effect on CD1d expressing malignancies as well as its ability to induce long-lasting anticancer CD8 T cell responses mediated through dendritic cell cross-priming and licensing. Several therapeutic techniques including the use of allogenic iNKT cells (both untransduced and CARs) are being developed, and we describe preliminary clinical investigations with IMM60, a synthetically produced iNKT cell agonist formulated in a liposome ( PORT-2). In preclinical investigations, IMM-60 administration resulted in DC and B cell maturation as well as strong activation of iNKT cell-derived IFN-g. IMM60 displayed monotherapy activity in PD-1 resistant models (e.g., B16-F10), up-regulation of PD-L1 expression on cancer cells as a result of its priming effect, and the ability to overcome resistance to PD-1 antibody therapy in efficacy tests.
Methodology:
IMP-MEL is a phase 1/2 open-label research presently enrolling adult patients with advanced NSCLC and melanoma. IMM60 liposomes were given IV Q3W at three ascending dose levels for six doses alone or with PEM 200mg Q3W. The purpose of the study is to evaluate the safety and efficacy of IMM-60 alone and in combination with PEM. Results: Five participants were included in the monotherapy cohort, with a median of three prior treatments (min 2, max 5). The average age was 64.5 years. To yet, no treatment-related adverse events or objective disease responses have been documented in the evaluable monotherapy individuals (n=3).
Findings:
At the levels examined, IMM-60 is well tolerated when provided IV as monotherapy. The liposomal formulation has a promising preliminary safety profile. The full phase 1 results, including circulating cytokine and flow cytometric analyses, will be presented during the symposium. The experiment will proceed to phase 2 comparing IMM60 alone versus PEM monotherapy versus the combination of IMM60 and PEM.