NCT06544265招募中1 期
A Phase 1 Study of SynKIR-310, Autologous T Cells Transduced With CD19 KIR-CAR, in Participants With Relapsed or Refractory B-Cell Non-Hodgkin Lymphoma
Verismo Therapeutics10 个研究点 分布在 1 个国家目标入组 36 人开始时间: 2024年11月1日最近更新:
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 36
- 试验地点
- 10
- 主要终点
- Recommended Phase 2 Dose (RP2D)
研究概览
简要总结
This first-in-human (FIH) trial is designed to assess the safety, feasibility and preliminary efficacy of a single intravenous (IV) dose of SynKIR-310 administered to participants with relapsed/refractory B-NHL.
详细描述
This is a Phase 1, FIH, multicenter, open-label study of a single infusion of SynKIR-310 in participants with relapsed/refractory B-NHL.
Up to 36 participants, regardless of subtypes of B-NHL, who meet the eligibility criteria, will be treated in the study.
Up to 4 cohorts of 3 to 6 participants per cohort will be assessed to determine the safety and feasibility of treatment with SynKIR-310. Doses will be escalated across up to 4 cohorts to determine a Recommended Phase 2 Dose (RP2D).
Once the RP2D has been determined, a dose expansion group will enroll additional participants regardless of subtypes of B-NHL at the RP2D to further characterize the safety, feasibility and preliminary efficacy of SynKIR-310 in treating B-NHL.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Adult 18 years of age and older.
- •Histologically confirmed diagnosis of B-NHL before enrollment.
- •Must have received prior CAR T or were unwilling/unable to receive prior CAR T.
- •Must have refractory or relapsed disease after receiving 2 prior lines of therapies.
- •If relapsed/refractory post-auto-SCT, then must have undergone auto-SCT at least 6 months prior to enrollment.
- •If relapsed/refractory disease after allogeneic stem cell transplant (allo SCT) then must have undergone allo-SCT at least 6 months prior to enrollment and without evidence of graft versus host disease, and expectation to remain off immunosuppressive therapy through duration of trial
- •Measurable disease at time of enrollment: At least one measurable lesion per Lugano Response Criteria (Cheson et al., 2014) or measurable disease per IWWM-11 response criteria (Treon 2023) for Waldenström macroglobulinemia patients.
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1
排除标准
- •Previously treated with any investigational agent within 30 days prior to screening.
- •Any previous or concurrent malignancy, with the following exceptions:
- •Adequately treated non-melanoma skin cancer such as basal cell or squamous cell carcinoma; carcinoma-in-situ (e.g., cervix, bladder, breast) treated curatively and without evidence of recurrence for at least 3 years prior to enrollment or adequately treated melanoma skin cancer in-situ; any other malignancy which has been completely treated and remains in complete remission for ≥ 5 years prior to enrollment. Completely treated prostate cancer with prostate-specific antigen (PSA) level < 1.0 may also be permitted.
- •Use of systemic immunosuppressive drugs within 4 weeks prior to study entry, or anticipated use of systemic immunosuppressive agents through end of study, with the exception of non-T cell targeting agents prior to leukapheresis
- •Known immunodeficiency disease , with the exception of hypoglobulinemia
- •History or presence of active or clinically relevant primary central nervous system (CNS) disorder, such as seizure, encephalopathy, cerebrovascular ischemia/hemorrhage, cerebellar disease, or any autoimmune disease with CNS involvement. For primary CNS disorders that have recovered or are in remission, participants without recurrence within 2 years of planned study enrollment may be included.
- •Uncontrolled hypertension, history of myocarditis or congestive heart failure, unstable angina, serious uncontrolled cardiac arrhythmia, or myocardial infarction within 6 months prior to study entry.
- •Any active uncontrolled systemic fungal, bacterial or viral infection.
- •Note: Other protocol defined Inclusion/Exclusion criteria may apply.
研究组 & 干预措施
SynKIR-310
Experimental
Single dose IV administration of SynKIR-310
干预措施: SynKIR-310 (Biological)
结局指标
主要结局
Recommended Phase 2 Dose (RP2D)
时间窗: Up to 24 months
All available data from dose escalation cohorts will be evaluated to determine RP2D
Evaluate the safety of SynKIR310
时间窗: Up to 24 months
The incidence, frequency, and severity of adverse events (AEs), including serious adverse events (SAEs), treatment-emergent adverse events (TEAEs), and dose-limiting toxicities (DLTs). Presence of RCL-VSV-G
次要结局
- Preliminary efficacy: Duration of response (DOR)(Up to 24 months)
- PK profile of SynKIR-310(Up to 24 months)
- Preliminary efficacy : Objective response rate (ORR)(Up to 24 months)
- Preliminary efficacy: Complete response rate (CR)(Up to 24 months)
- PD profile of SynKIR-310(Up to 24 months)
- Feasibility of SynKIR-310(Up to 24 months)
研究者
研究点 (10)
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相关资讯
Verismo Therapeutics Expands KIR-CAR Solid Tumor Pipeline with Novel CLDN6 Binder from Penn Collaboration- Verismo Therapeutics has secured a novel CLDN6-targeted binder through a research collaboration with the University of Pennsylvania, expanding its KIR-CAR platform into a second solid tumor antigen program.
- CLDN6 is a clinically validated solid tumor target with limited expression in healthy adult tissues, already being pursued via CAR-T, ADC, and bispecific antibody modalities.
- The new preclinical program complements the clinical-stage SynKIR-110 targeting mesothelin, which recently reported early signals of tumor reduction in the STAR-101 Phase 1 trial.
- Verismo's multi-chain KIR-CAR platform is designed to overcome persistence and T-cell exhaustion limitations that have hindered conventional CAR-T therapies in solid tumors.last monthVerismo Therapeutics Reports First Clinical Data for Novel Multi-Chain KIR-CAR Therapies at AACR 2026- Verismo Therapeutics will present initial Phase 1 clinical data for SynKIR™-110 in mesothelin-expressing solid tumors and early data for SynKIR™-310 in B cell non-Hodgkin lymphomas at AACR 2026.
- The company's multi-chain KIR-CAR platform represents the first KIR-CAR-based immuno-oncology therapies in human trials, designed to overcome limitations of traditional CAR T therapies.
- The novel technology uses natural killer cell biology to address "always-on" tonic signaling and T cell exhaustion that limit current single-chain CAR T treatments.
- Preclinical data shows the KIR-CAR platform outperforms conventional CAR T therapies in xenograft models and demonstrates resistance to tumor immunosuppression.6 months agoVerismo's Novel KIR-CAR Platform Shows Superior Tumor Control with Reduced Toxicity in Preclinical Studies- Verismo Therapeutics presented preclinical data at ASH 2025 showing SynKIR™-310 achieved faster and deeper tumor control compared to conventional CD19 CAR-T therapies like tisagenlecleucel.
- The novel KIR-CAR signaling platform demonstrated superior anti-tumor activity while producing substantially lower levels of inflammatory cytokines in mouse models.
- SynKIR™-310 is currently being evaluated in a Phase 1 clinical trial for patients with relapsed/refractory B-cell non-Hodgkin lymphoma, including those previously treated with CD19 CAR-T therapies.
- The technology addresses key limitations of current CAR-T treatments, including T cell exhaustion and cytokine release syndrome that affects many patients.9 months agoVerismo Therapeutics' Novel KIR-CAR Platform Shows Enhanced Safety and Efficacy in Solid Tumor Preclinical Studies- Verismo Therapeutics presented preclinical data at SITC 2025 showing SynKIR™-110 demonstrated reduced cell exhaustion and lower off-target toxicity compared to conventional CAR T therapies.
- The novel KIR-CAR platform achieved sustained tumor killing and deep regression in mesothelioma mouse models while showing selective enrichment in tumors rather than normal tissues.
- SynKIR™-110 is currently in Phase 1 clinical trials for advanced ovarian cancer, cholangiocarcinoma, and mesothelioma, with FDA Orphan Drug and Fast Track designations for mesothelioma treatment.
- The company's oral presentation was selected as one of the top 150 abstracts from over 1,300 submissions at the SITC 2025 Annual Meeting.10 months agoVerismo Therapeutics Partners with Miltenyi Biotec to Advance KIR-CAR Platform for Solid Tumor Treatment- Verismo Therapeutics successfully manufactured its first clinical cell product using lentiviral vector supplied by Miltenyi Bioindustry for the STAR-101 Phase 1 trial.
- The collaboration supports SynKIR™-110, a novel KIR-CAR therapy targeting mesothelin for solid tumor treatment, marking a major milestone in clinical development.
- This partnership establishes a reliable supply chain for Phase 2 development and commercial applications of Verismo's unique multi-chain KIR-CAR platform technology.
- The KIR-CAR platform uses modified NK cell-derived receptors designed to improve T cell persistence and reduce exhaustion in challenging tumor microenvironments.11 months ago
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