Clinical trial NCT06544265: SynKIR-310 for Relapsed/Refractory B-NHL
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: B Cell Lymphoma
NHL, Adult
Mantle Cell Lymphoma
Relapsed Non-Hodgkin Lymphoma
Refractory Non-Hodgkin Lymphoma
Aggressive B-Cell Non-Hodgkin Lymphoma
Indolent B-Cell Non-Hodgkin Lymphoma
Follicular Lymphoma
Marginal Zone Lymphoma
DLBCL - Diffuse Large B Cell Lymphoma
HGBL With MYC and BCL2 and/or BCL6 Rearrangements
High-grade B-cell Lymphoma
Diffuse Large B Cell Lymphoma
Large B-cell Lymphoma
T-Cell/Histiocyte Rich Lymphoma
Non-hodgkin Lymphoma,B Cell
Primary Mediastinal Large B-cell Lymphoma (PMBCL)
Epstein-Barr Virus Positive DLBCL, Nos
Follicular Lymphoma Grade 3B
DLBCL (Diffuse Large B-Cell Lymphoma) Associated With Chronic Inflammation
High Grade B-Cell Lymphoma, Not Otherwise Specified
Follicular Lymphoma Grade 3
Marginal Zone Splenic Lymphoma
DLBCL
Lead sponsor: Verismo Therapeutics
Sponsor class: INDUSTRY
First posted: 2024-08-09
Enrollment: 18
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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 18 participants, regardless of subtypes of B-NHL, who meet the eligibility criteria, will be treated in the study.

2 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 2 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.

Eligibility criteria: 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.
* Measurable disease at time of enrollment: At least one measurable lesion per Lugano Response Criteria (Cheson et al., 2014).
* 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.
* 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.
* 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.
* Known immunodeficiency disease.
* 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.

Primary outcomes:
measure: Evaluate the safety of SynKIR310
timeFrame: Up to 24 months
measure: Recommended Phase 2 Dose (RP2D)
timeFrame: Up to 24 months
Secondary outcomes:
measure: Feasibility of SynKIR-310
timeFrame: Up to 24 months
measure: Preliminary efficacy : Objective response rate (ORR)
timeFrame: Up to 24 months
measure: Preliminary efficacy: Complete response rate (CR)
timeFrame: Up to 24 months
measure: Preliminary efficacy: Duration of response (DOR)
timeFrame: Up to 24 months
measure: PD profile of SynKIR-310
timeFrame: Up to 24 months
measure: PK profile of SynKIR-310
timeFrame: Up to 24 months
Other outcomes:
Locations:
city: Denver
country: United States
facility: Colorado Blood Cancer Institute, part of Sarah Cannon Cancer Institute
state: Colorado
city: Fairway
country: United States
facility: The University of Kansas Cancer Center
state: Kansas
Study officials:
affiliation: Verismo Therapeutics
name: Laura A Johnson, PhD
role: STUDY_CHAIR
References: