Date: 2016-11-09
Type of information: Presentation of results at a congress
phase: 1
Announcement: presentation of results at the Society for Immunotherapy of Cancer (SITC) 31stAnnual Meeting & Associated Programs
Company: Curis (USA - MA)
Product: CA-170
Action
mechanism: immune checkpoint inhibitor. CA-170 is a first-in-class, orally available, small molecule that is designed to specifically target and inhibit the immune checkpoints, Programmed Death Ligand-1 (PD-L1) and V-domain Immunoglobulin Suppressor of T-cell Activation (VISTA). Preclinical ex vivo experiments demonstrated that CA-170 induced effective proliferation and cytokine production by T cells that are specifically suppressed by PD-L1 or VISTA. In subsequent preclinical in vivo studies, CA-170 showed significant anti-tumor activity, similar to anti-PD-1 antibodies, in multiple tumor models. In preclinical toxicology studies, CA-170 was considered to be safe when administered at multiple dose levels using a once daily oral dosing schedule. CA-170 is being developed under a collaboration and licensing agreement with Aurigene.
Disease: advanced solid tumors, lymphoma
Therapeutic area: Cancer - Oncology
Country: USA
Trial
details: CA-170 is a rationally designed and orally available, small molecule that directly targets the Programmed death-ligands 1 and 2 (PD-L1/PD-L2), and V-domain Ig suppressor of T cell activation (VISTA) immune checkpoints and results in activation of T cell proliferation and cytokine production. This is a multi-center, open-label, Phase 1 trial of orally administered CA-170 in adult patients with advanced solid tumors or lymphomas who have progressed or are non-responsive to available therapies and for which no standard therapy exists. (NCT02812875)
Latest
news: * On November 9, 2016, Curis presented preliminary clinical pharmacokinetic (PK) and early biomarker data from the ongoing dose escalation stage of CA-170's Phase 1 trial at the Society for Immunotherapy of Cancer (SITC) 31stAnnual Meeting & Associated Programs in National Harbor, MD. Preclinical data presented previously demonstrated dose-dependent oral exposure in multiple non-clinical models, as well as immune modulation and anti-tumor activity with CA-170 in multiple syngeneic mouse tumor models. Clinical data from a limited number of patients in the Phase 1 trial presented at the SITC conference, demonstrate that similar to the preclinical findings, CA-170 has a dose proportional and predictable PK profile in patients treated orally at various doses in the ongoing dose escalation stage of the study. Further, evaluation of patient blood samples demonstrate that CA-170 appears to be biologically active in modulating the immune system, with a several-fold increase in percentage of circulating CD8+ T cells expressing activation markers within 24 hours of oral dosing. * On June 21, 2016, Curis, announced that the first patient was dosed in a Phase 1 trial of CA-170.The Phase 1 study is designed to: (1) evaluate the safety, tolerability, and pharmacokinetic profile of CA-170; (2) identify any dose-limiting toxicities; and (3) establish the recommended Phase 2 dose (RP2D) of CA-170 in patients with advanced solid tumors or lymphoma. During the expansion stage, the study is expected to assess the anti-cancer activity of CA-170 at the RP2D in patients with specified cancer types. * On June 1, 2016, Curis announced that the FDA has accepted the company's Investigational New Drug (IND) application for CA-170.
