Verismo Therapeutics has initiated patient dosing in its Phase 1 CELESTIAL-301 trial, evaluating SynKIR-310, a novel CAR T-cell therapy, for relapsed/refractory B cell Non-Hodgkin Lymphomas (B-NHL). The first patient was dosed at the Sarah Cannon Research Institute of Colorado Blood Cancer Institute in Denver, Colorado. This multicenter trial aims to assess the safety, tolerability, and preliminary efficacy of SynKIR-310 in patients with various subtypes of B-NHL, including Diffuse Large B Cell lymphoma (DLBCL), Follicular Lymphoma (FL), Mantle Cell Lymphoma (MCL), and Marginal Zone Lymphoma (MZL).
The CELESTIAL-301 trial is enrolling patients who have either relapsed after prior CAR T-cell therapy or have never received it. The trial design includes two cohorts, each with three to six patients, to evaluate safety and feasibility. Dose escalation will be conducted to establish a Recommended Phase II Dose (RP2D), followed by a dose expansion group to further assess SynKIR-310 at the RP2D, regardless of B-NHL subtype.
Addressing Unmet Needs in B-NHL Treatment
Approved CAR T-cell therapies have demonstrated high initial response rates in blood cancers; however, an estimated 40-50% of patients relapse due to a lack of long-term T cell effector function and persistence. Limited treatment options exist for patients with r/r DLBCL who relapse following CAR T-cell therapy. SynKIR-310 is designed to address these unmet needs by prolonging T cell functional persistence and overcoming challenges of disease relapse.
SynKIR-310: A Novel KIR-CAR T-cell Therapy
SynKIR-310 utilizes Verismo's unique KIR-CAR platform and proprietary CD19 binder (DS191). Targeting CD19, similar to commercially approved CAR T-therapies, SynKIR-310 aims to enhance anti-tumor T cell function and persistence, potentially preventing early disease relapse in patients with advanced B cell lymphomas. The KIR-CAR platform is a multi-chain CAR T-cell therapy that has shown the ability to maintain antitumor T cell activity in challenging tumor microenvironments in preclinical animal models.
Expert Perspectives
"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," said Dr. Laura Johnson, Chief Operations Officer and Chief Scientific Officer at Verismo Therapeutics. "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."
Michael Tees, MD, the principal investigator at SCRI at Colorado Blood Cancer Institute (CBCI), added, "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."
Trial Design and Endpoints
The primary endpoints of the CELESTIAL-301 study include assessing the incidence, frequency, and severity of adverse events (AEs) and determining the RP2D of SynKIR-310. Secondary endpoints will evaluate the feasibility of SynKIR-310, objective response rate, complete response rate, duration of response, pharmacodynamics, and pharmacokinetics. The trial aims to enroll up to 18 patients with R/R B-NHL, regardless of subtype, who meet eligibility criteria, including those who have relapsed after two prior lines of therapy and have measurable disease.
