Aggressive B-Cell Non-Hodgkin Lymphoma, B Cell Lymphoma, Diffuse Large B Cell Lymphoma, DLBCL, DLBCL - Diffuse Large B Cell Lymphoma, DLBCL (Diffuse Large B-Cell Lymphoma) Associated With Chronic Inflammation, Epstein-Barr Virus Positive DLBCL, Nos, Follicular Lymphoma, Follicular Lymphoma Grade 3, Follicular Lymphoma Grade 3B, HGBL With MYC and BCL2 and/or BCL6 Rearrangements, High-grade B-cell Lymphoma, High Grade B-Cell Lymphoma, Not Otherwise Specified, Indolent B-Cell Non-Hodgkin Lymphoma, Large B-cell Lymphoma, Mantle Cell Lymphoma, Marginal Zone Lymphoma, Marginal Zone Splenic Lymphoma, NHL, Adult, Non-hodgkin Lymphoma,B Cell, Primary Mediastinal Large B-cell Lymphoma (PMBCL), Refractory Non-Hodgkin Lymphoma, Relapsed Non-Hodgkin Lymphoma, T-Cell/Histiocyte Rich Lymphoma, Waldenstrom Macroglobulinaemia, Waldenstrom Macroglobulinemia
Conditions
Brief summary
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.
Detailed description
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.
Interventions
Autologous T Cells transduced with CD19 KIR-CAR
Sponsors
Study design
Eligibility
Inclusion criteria
* 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
Exclusion criteria
* 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/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Evaluate the safety of SynKIR310 | 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 |
| Recommended Phase 2 Dose (RP2D) | Up to 24 months | All available data from dose escalation cohorts will be evaluated to determine RP2D |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Feasibility of SynKIR-310 | Up to 24 months | Number of enrolled patients who pass screening but do not receive SynKIR-310 |
| Preliminary efficacy : Objective response rate (ORR) | Up to 24 months | Percentage of patients with a complete or partial response determined by Investigator |
| Preliminary efficacy: Complete response rate (CR) | Up to 24 months | Percentage of patients with a Complete Response determined by Investigator |
| Preliminary efficacy: Duration of response (DOR) | Up to 24 months | Time from the date of the first occurrence of complete response or partial response to the date of progression, relapse, or death from any cause, determined by Investigator |
| PK profile of SynKIR-310 | Up to 24 months | To evaluate the patients who show CAR T persistence in blood (measured in the blood by quantitative polymerase chain reaction (PCR)) at multiple study time points following SynKIR-310 infusion |
Countries
United States
Contacts
Verismo Therapeutics