Verismo Therapeutics’ Trial for R/R B-NHL CAR-T SynKIR-310 Doses First Patient
The multicenter trial is open to patients with forms of r/r B-NHL including DLBCL, FL, MCL, and MZL.
The first patient has been dosed in Verismo Therapeutics’ phase 1 CELESTIAL-301 clinical trial (NCT06544265), which is evaluating SynKIR-310, a chimeric antigen receptor T-cell (CAR-T) therapy based on the company's killer immunoglobulin-like receptor (KIR)-CAR platform, in patients with relapsed/refractory (r/r) B-cell nonHodgkin lymphoma (B-NHL).1
The multicenter trial is open to patients with forms of r/r B-NHL including diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), mantle cell lymphoma (MCL), and marginal zone lymphoma (MZL). Notably, the study is open to patients who have previously received another CAR-T therapy but whose disease relapsed or was refractory to the therapy, as well as patients who have never previously received a CAR-T product. The first patient’s dosing took place in Denver, Colorado at the Sarah Cannon Research Institute (SCRI) at Colorado Blood Cancer Institute (CBCI).
SynKIR-310 is based on Verismo’s KIR-CAR platform, which was developed at the University of Pennsylvania, and is intended to enable sustained antitumor activity of the CAR T-cells in difficult tumor microenvironments.2 KIR-CAR is a dual-chain CAR T-cell platform that uses a natural killer cell derived KIR and DAP12, which acts as a novel costimulatory molecule for T-cells, to improve expression and persistence.1,2 In preclinical models resistant to traditional CAR-T approaches it showed prolonged functional T-cell persistence and effected tumor regression.2,3
"The initiation of patient dosing in the CELESTIAL-301 trial marks an exciting milestone for Verismo Therapeutics as we advance our mission to develop transformative therapies for patients facing advanced lymphomas,” Laura Johnson, PhD, the chief operations officer and chief scientific officer at Verismo, said in a statement.1 “CBCI's commitment to patients and to conducting novel early-stage clinical trials has allowed us to reach this milestone earlier than expected. SynKIR-310 is uniquely designed to prolong T-cell functional persistence and combat the challenges of disease relapse, offering a potentially life-saving option for these patients."
The investigational new drug (IND) application enabling CELESTIAL-301 was cleared by the FDA in May 2024.3 The trial is open to adult patients and is expected to enroll approximately 18 patients in total.
"We are thrilled to administer this promising therapy," Michael Tees, MD, the principal investigator at SCRI, added to the statement.1 "Emerging treatments like SynKIR-310 have potential to reshape care for patients with advanced lymphomas, offering new hope. This milestone showcases the impact of CBCI and other expert research centers in advancing early-stage clinical trials."
SynKIR-310 is not the company’s only CAR-T therapy based on the KIR-CAR platform that is currently in clinical development. Verismo is also developing SynKIR-110, which combines an mesothelin (MSLN)-specific antibody with natural killer cell signals to target MSLN-expressing tumors, and is being assessed for the treatment MSLN-expressing pleural mesothelioma, cholangiocarcinoma, or ovarian cancer in the the first-in-human phase 1/2 STAR-101 study (NCT05568680).3 The trial, which is taking place at the University of Pennsylvania, dosed its first patient in September 2023, following a September 2022 IND clearance.4,5
"Preclinical data have shown enhanced efficacy in murine models with no additional safety concerns,” Bryan Kim, DMD, the chief executive officer of Verismo, said in a September 2022 statement.5 “The FDA's clearance of our SynKIR-110 IND represents a new chapter for Verismo as we initiate the first-ever clinical trial for KIR-CAR T-cells. It also validates the years of innovative research and hard work by industry pioneers at Penn and the Verismo team.”
