Part B (bottom): patients received efti (30 mg) with cycle 1 of pembrolizumab for up to 12 months. Pembrolizumab was given at a dose of 2 mgkg intravenous every 3 weeks efti was given as subcutaneous (s.c.) injection of 1 mg (cohort 1), 6 mg (cohort 2) or 30 mg (cohort 3) every 2 weeks for approximately 6 months, starting with cycle 5 of pembrolizumab.Įligible patients received efti (1, 6, 30 mg) with cycle 5 of pembrolizumab for up to 6 months. Disable macros in word for macĮffect of efti versus an anti-LAG-3 antagonist antibody on the immune response. This therapeutic approach is fundamentally different from the mainstream two-ICI approach (ie, anti-LAG-3anti-PD-1 monoclonal antibody (mAbs)) as efti is an agonist acting on APC and anti-LAG-3 mAb is an antagonist acting on T cells, see figure 1. The present TACTI-mel (Two ACTive Immunotherapies in melanoma) phase I trial is testing this combined push (systemic APC activation) and pull (ICI) approach in metastatic melanoma. Interest in the clinical use of TLR and CD40 agonistic antibodies in immuno-oncology wavered in the past decade, 2 but recent clinical data are encouraging. Professional APCs express major histocompatibility complex (MHC) class II and CD40 molecules as surface receptors and can be activated through direct interactions with T cells expressing these receptors corresponding ligands, lymphocyte activation gene-3 (LAG-3) and CD40-L, respectively.Ī third class of receptors that can activate APCs are called toll-like receptors (TLRs) and bind foreign ligands that are structurally conserved molecules from microbes. This warrants further clinical studies of this new combination therapy combining an antigen-presenting cell activator with an immune checkpoint inhibitor.Ĭombinatorial approaches that target multiple aspects of the cancer immunity cycle, 1 including APC activation, are promising strategies for the treatment of cancer. Treatment induced an increase in activated CD8 and CD4 T cell counts, and in some of the soluble biomarkers, particularly interferon (IFN)-, a Th1 signature cytokine.Īn overall response rate (ORR) of 33 was observed in patients partly with pembrolizumab-refractory of part A and ORR of 50 was observed in patients with PD-1 nave of part B.Ĭonclusions Efti was well tolerated in combination with pembrolizumab with encouraging antitumor activity.
Sustained systemic exposure to the product was obtained in all patients following s.c. No dose-limiting toxicities were reported and the main adverse event for efti was injection site reactions. Results Twenty-four patients with melanoma received pembrolizumab and bi-weekly subcutaneous (s.c.) injections of efti at doses 1 mg, 6 mg or 30 mginjection for up to 6 months (part A) or 30 mginjection for up 12 months (part B). Software Lag Switch 1.2 Plus The Standard.
0 kommentar(er)
