Verismo Therapeutics, a clinical-stage CAR-T company, has announced the activation of its CELESTIAL-301 Phase 1 clinical trial at the Sarah Cannon Research Institute (SCRI) at Colorado Blood Cancer Institute (CBCI). This trial aims to evaluate the safety, tolerability, and preliminary efficacy of SynKIR™-310 in patients with relapsed/refractory (r/r) B-cell Non-Hodgkin Lymphomas (B-cell NHL). The study is enrolling patients who have previously received CAR T-cell therapy and have relapsed or become refractory, as well as those who have not received prior CAR T-cell therapy.
Addressing Unmet Needs in B-cell NHL Treatment
The CELESTIAL-301 trial seeks to address the significant unmet medical need in treating B-cell NHL. While commercially approved CAR T-cell therapies have demonstrated high initial response rates in blood cancers, an estimated 40-50% of patients relapse over time. These relapses are often due to a lack of long-term T-cell effector function and persistence. Currently, treatment options are limited for patients with r/r Diffuse Large B Cell Lymphoma (DLBCL) who relapse following CAR T-cell therapy. Ongoing clinical investigations have yet to fully address this critical need.
SynKIR™-310: A Novel Approach
SynKIR™-310 is based on Verismo’s unique KIR-CAR platform and utilizes a proprietary CD19 binder (DS191). This therapy targets a similar epitope of CD19 as commercially available CAR T-cell therapies but is designed to prolong anti-tumor T-cell function and persistence. The potential improvement in KIR-CAR T-cell persistence could prevent early disease relapse in patients with aggressive lymphomas.
Dr. Laura Johnson, CSO of Verismo Therapeutics, stated, "This trial embodies Verismo's continued commitment to combatting advanced cancers and addressing high areas of unmet medical need. SynKIR™-310 has significant potential to help patients with B-cell Non-Hodgkin Lymphomas and be especially beneficial for patients that relapsed after previous infusions of CAR T cell therapies."
Trial Design and Patient Population
The Phase 1 multicenter clinical trial will include patients with various subtypes of r/r B-cell NHL, including DLBCL, Follicular Lymphoma (FL), Mantle Cell Lymphoma (MCL), and Marginal Zone Lymphoma (MZL). The trial will assess the safety, tolerability, and preliminary efficacy of SynKIR™-310. Verismo received IND clearance from the FDA in May 2024 to proceed with this trial. SynKIR™-310 is Verismo's second clinical pipeline asset, following SynKIR™-110, which targets aggressive mesothelin-expressing solid tumors. Additional information about the CELESTIAL-101 clinical trial can be found on ClinicalTrials.gov (NCT06544265).
About the KIR-CAR Platform
The KIR-CAR platform is a multi-chain CAR T-cell therapy designed to maintain antitumor T-cell activity even in challenging tumor microenvironments. By utilizing NK cell-derived KIR and DAP12 split signaling, the platform provides a novel combination of activation and co-stimulation, separate from traditional T-cell stimulation pathways. This approach enables sustained chimeric receptor expression and improves long-term KIR-CAR T-cell function, leading to prolonged T-cell functional persistence and regression of solid tumors and blood cancers in preclinical models resistant to traditional CAR T-cell therapies.
