Achieves 60% complete remission in relapsed and refractory blood cancer patients with no major immunotoxicity
Safety profile expected to contrast with early clinical trials of Yescarta and Kymriah; high-dose trial results slated for release in December
Dubbed a "miracle cancer drug," CAR-T cell therapy has transformed blood cancer treatment, yet relapse and immunotoxicity remain persistent challenges. SynKIR-310, a next-generation CAR-T therapy developed by Verismo Therapeutics—a US subsidiary of HLB Innovation(024850)—is taking on these limitations. In clinical trials involving blood cancer patients who relapsed or failed to respond to conventional therapies, the treatment achieved a complete remission rate of 60%, with no major immunotoxicities observed.
The latest clinical trial included elderly, high-risk patients. Unlike the early clinical trials of previously approved CAR-T therapies, which induced immunotoxicity in a significant number of patients, SynKIR-310 demonstrated anti-tumor responses while avoiding major immunotoxicities. Additional trial results featuring significantly higher dosage levels are scheduled to be unveiled this coming December.
60% Complete Remission in Elderly, High-Risk Blood Cancer Patients
According to a Phase I clinical abstract released by the American Society of Hematology (ASH) on the 4th (local time), Verismo administered SynKIR-310 to six patients with relapsed or refractory B-cell non-Hodgkin lymphoma. The patients had undergone at least two prior lines of therapy, with a median age of 72. All patients presented with stage 3 or 4 advanced lymphoma, and all three patients with aggressive lymphoma exhibited complex "double-hit" or "triple-hit" genetic abnormalities, which are notoriously difficult to treat.
Among the five evaluable patients, four exhibited a therapeutic response, with three achieving complete remission (CR), showing no detectable signs of cancer. One patient who achieved complete remission maintained their response at the 12-month mark.
The safety profile is equally noteworthy. None of the six treated patients experienced cytokine release syndrome (CRS) or immune effector cell-associated neurotoxicity syndrome (ICANS)—the signature adverse effects of CAR-T therapies. Furthermore, no dose-limiting toxicities or treatment-related serious adverse events were reported. Grade 4 neutropenia and leukopenia were each observed in one patient.
Despite their high efficacy, conventional CAR-T therapies carry a heavy burden of immunotoxicity. In Gilead Sciences' ZUMA-1 Phase I trial for Yescarta, CRS developed in six out of seven patients, while neurotoxicity of grade 3 or higher occurred in four. Similarly, early studies of Novartis' Kymriah reported severe CRS in five out of 28 patients and neurological adverse events in 11.
While direct comparisons are limited due to differing patient demographics and evaluation criteria across trials, SynKIR-310 demonstrated a potential differentiator in safety by avoiding the major immunotoxicities seen in early studies of approved CAR-T treatments.
Kim Hyun-seok, an analyst at Hyundai Motor Securities, noted, "The most positive takeaway is that neither CRS nor ICANS—even at Grade 1—was observed, despite administering the therapy to elderly patients. Achieving complete remission without triggering major immunotoxicities marks a distinguishing early result compared to legacy CAR-T therapies."
He attributed SynKIR-310's selection for an ASH oral presentation to the recognition of these robust safety profiles. Having confirmed early potential in efficacy as well, further evaluation of Cohort 3 results and therapeutic responses across lymphoma subtypes will help clarify its differentiation from existing approved drugs, he added.
If subsequent clinical trials consistently replicate this combination of potent anti-tumor efficacy and low immunotoxicity, KIR-CAR could offer a novel solution to safety concerns, which have long been one of the heaviest burdens associated with traditional CAR-T therapies.
KIR-CAR Minimizes Immune Response… Staged for 1 Billion-Cell High-Dose Trial
KIR-CAR, developed by Verismo, features a receptor design distinct from conventional CAR-T therapies. It separates the cancer-recognizing domain from the T-cell activation signaling domain and incorporates DAP12, a signaling protein derived from natural killer (NK) cells. Through this multi-chain receptor architecture, Verismo aims to sustain anti-tumor activity while mitigating excessive immune responses.
The technical advantages of KIR-CAR were also evident in preclinical studies previously released by Verismo. In animal experiments presented at last year's ASH, SynKIR-310 demonstrated faster and more robust tumor suppression at lower doses compared to conventional single-chain CAR-T therapies. On the 13th day of the experiment, cytokine levels in the conventional single-chain CAR-T control group were significantly higher than those in the SynKIR-310 and other KIR-CAR treatment groups—specifically 37 times higher for IFN-γ, 27 times higher for TNF-α, and 17 times higher for IL-2. Verismo is scheduled to present additional preclinical data directly comparing the two technologies at this year's ASH as well.
The cell doses administered in the current trial were 100 million for the first dose cohort and 300 million for the second. By comparison, the maximum FDA-approved dose for Yescarta is 200 million cells, while Kymriah's authorized adult lymphoma dosage ranges from 60 million to 600 million cells. Although cell-counting methodologies and product characteristics vary, SynKIR-310 showed an absence of major immunotoxicities at dose levels overlapping with those of currently approved therapies.
The next testing ground is the third dose cohort, which administers a massive 1 billion cells. This trial will evaluate anti-tumor efficacy and immunotoxicity at a dosage approximately 3.3 times higher than the previous 300-million-cell cohort.
"With traditional CAR-T therapies, increasing the dosage tends to escalate the toxicity burden without yielding proportional gains in efficacy," Analyst Kim stated. "Given that SynKIR-310 has shown no major immunotoxicity thus far, the critical question is whether higher doses will unlock deeper therapeutic responses."
He added that because approved CAR-T treatments already exhibit high response rates in certain subtypes such as follicular and marginal zone lymphoma, it remains necessary to examine patient-specific responses alongside additional data from Cohort 3.
Verismo is slated to disclose additional Phase I results from Cohort 3, alongside pharmacokinetic and pharmacodynamic (PK/PD) analysis data, during a regular oral presentation at ASH on December 13. Attention is focused on forthcoming data concerning safety, anti-tumor responses, and the in vivo proliferation and persistence of therapeutic cells in patients receiving the escalated 1-billion-cell dose.
