In:
Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 40, No. 16_suppl ( 2022-06-01), p. 2582-2582
Kurzfassung:
2582 Background: Invariant natural killer T-cells (iNKTs) share features of innate cells (NK-like) and T-cells (can prime and boost an adaptive immune response). The importance of this relatively rare lymphocyte subset has generated increased interest due to its dual ability to have a direct cytotoxic effect on CD1d expressing tumors and also its ability to induce long-lasting antitumor CD8 T cell responses mediated by cross priming and licensing of dendritic cells. Various clinical approaches involving the use of allogenic iNKT cells (both untransduced and CARs) are in development and here we describe initial clinical studies with IMM60, a synthetically derived agonist of iNKT cells which is formulated in a liposome( PORT-2). In preclinical studies, IMM-60 treatment results in maturation of DCs and B cells and a potent stimulation of iNKT cell-derived IFN-g. In efficacy studies, IMM60 demonstrated monotherapy activity in PD-1 resistant models, (eg., B16-F10), up-regulation of PD-L1 expression on cancer cells as a consequence of its priming effect, and was able to overcome resistance to PD-1 antibody therapy. Methods: IMP-MEL is an open-label first-in-man phase 1/2 study, currently enrolling adult subjects with advanced NSCLC and melanoma. IMM60 containing liposomes were administered IV Q3W at 3 escalating dose levels for 6 doses alone or with PEM 200mg Q3W. The study seeks to assess the safety and efficacy of IMM-60 alone and in combination with PEM. Results: 5 subjects have been enrolled in the monotherapy cohort having a median of 3 prior therapies (min 2, max 5). Median age was 64.5 years. No treatment related adverse events have been reported nor any objective disease responses in the evaluable monotherapy subjects (n=3) to date. Conclusions: IMM-60 is well tolerated when administered IV as monotherapy at the doses tested. The liposomal formulation leads to a favorable preliminary safety profile. Full results of the phase 1 will be reported at the meeting with analysis of circulating cytokines and flow cytometric analysis. The trial plans to transition to phase 2 testing IMM60-alone vs PEM monotherapy vs the combination of IMM60 with PEM. Clinical trial information: 80472712.
Materialart:
Online-Ressource
ISSN:
0732-183X
,
1527-7755
DOI:
10.1200/JCO.2022.40.16_suppl.2582
Sprache:
Englisch
Verlag:
American Society of Clinical Oncology (ASCO)
Publikationsdatum:
2022
ZDB Id:
2005181-5
