SynKIR-310 for Relapsed/Refractory B-NHL

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.

• SynKIR-310 (Biological): Autologous T Cells transduced with CD19 KIR-CAR

Primary outcomes

• 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 outcomes

• 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

Sex: All, ages: 18 Years to any

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/Exclusion criteria may apply.

• Laura A Johnson, PhD, Study chair, Verismo Therapeutics