Four out of five evaluable patients responded to SynKIR-310, and three of the six treated received it as outpatients. Those two numbers define what Verismo Therapeutics is bringing to the oral session at the 68th ASH Annual Meeting in December, and they set a direct challenge to the toxicity profiles that have defined the CAR-T field since its earliest approvals.
The Phase 1 CELESTIAL-301 trial enrolled patients with relapsed or refractory B-cell non-Hodgkin lymphoma after at least two prior lines of therapy, the same population where approved CD19-directed therapies carry well-documented toxicity burdens. In the ZUMA-1 trial, axicabtagene ciloleucel has carried well-documented rates of Grade 3 or higher neurologic events in its pivotal trial. Across dose cohorts 1 and 2 of CELESTIAL-301, SynKIR-310 produced zero cytokine release syndrome or ICANS of any grade, and no dose-limiting toxicities. The 80% objective response rate and 60% complete response rate come from only five evaluable patients, so statistical weight is limited, but the safety signal across all six treated patients is unambiguous at these early dose levels.
The mechanism behind that profile is structural. SynKIR-310 uses a multi-chain KIR-CAR design that splits target binding and T cell activation across separate receptor components derived from NK cell biology, specifically a killer immunoglobulin-like receptor paired with DAP12, rather than relying on CD3 signaling. The company argues this reduces the background activation that drives early T cell exhaustion in conventional single-chain constructs. Two preclinical posters at ASH will add supporting evidence: one showing a head-to-head comparison where SynKIR-310 achieved deeper tumor control than single-chain CD19 CAR-T designs with substantially lower cytokine output, and a second presenting a CD19/CD20 dual-targeted construct aimed at antigen heterogeneity, which is a recognized driver of relapse after CD19-directed therapy. The duration-of-response data is also notable: the median was not reached among complete responders, with one patient still in complete response at the 12-month assessment.
The ASH oral session on December 13 will add dose cohort 3 data alongside pharmacokinetic and pharmacodynamic correlatives, which should clarify whether the clean safety profile holds as dosing increases. That is the number to watch.
Jon Napitupulu is Director of Media Relations at The Clinical Trial Vanguard. Jon, a computer data scientist, focuses on the latest clinical trial industry news and trends.
