Natural Killer (NK) Cell Therapy for B-Cell Malignancies

Study Overview
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Brief Summary
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This is an open-label, Phase I study of QN-019a (allogeneic CAR-NK cells targeting CD19) as monotherapy in relapsed/refractory B-cell Acute Lymphoblastic Leukemia (B-ALL) and in combination with Rituximab in relapsed/refractory B-cell Lymphoma. This clinical study is to evaluate the safety, tolerability and preliminary efficacy of QN-019a in patients with relapsed/refractory B-cell lymphoma or B-ALL. Up to 22-36 patients will be enrolled.

Detailed Description
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This is an open-label, Phase I study of QN-019a (allogeneic CAR-NK cells targeting CD19) as monotherapy in relapsed/refractory B-cell Acute Lymphoblastic Leukemia (B-ALL) and in combination with Rituximab in relapsed/refractory B-cell Lymphoma. This clinical study is to evaluate the safety, tolerability and preliminary efficacy of QN-019a in patients with relapsed/refractory B-cell lymphoma or B-ALL, where a 3+3 enrollment schema will be utilized at dose escalation stage. Up to 24-36 patients will be enrolled.

Official Title
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QN-019a as a Monotherapy and in Combination With Anti-CD20 Monoclonal Antibodies in Subjects With B-Cell Malignancies

Conditions
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B-cell Lymphoma, B-cell Acute Lymphoblastic Leukemia

Intervention / Treatment
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* Drug: QN-019a
* Drug: Rituximab
* Drug: Cyclophosphamid
* Drug: Fludarabine
* Drug: VP-16


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Diagnosis of B-cell lymphoma or B-ALL as described below: B-cell Lymphoma: Histologically documented lymphomas expected to express CD19 and CD20 Relapsed/refractory disease following at least two prior systemic treatment regimens, or relapsed after the autologous hematopoietic stem cell transplantation (HSCT) B-ALL: Diagnosis of B-ALL that expected to express CD19 Relapsed/refractory disease following prior systemic treatment regimens ALL SUBJECTS: Provision of signed and dated informed consent form (ICF) Age ≥ 18 years old Stated willingness to comply with study procedures and duration Eastern Cooperative Oncology Group (ECOG) performance status ≤1 Adequate organ function as defined in the protocol Donor specific antibody (DSA) to QN-019a: MFI <= 2000 At least 3 weeks after the last systemic immunochemotherapy treatment The estimated survival days are expected to be over 3 months Key Exclusion Criteria: ALL SUBJECTS: Females who are pregnant or lactating Evidence of insufficient organ function as defined in the protocol ECOG Performance Status ≥2 Prior allogeneic hematopoietic stem cell transplant (HSCT) or allogeneic CAR-T/CAR-NK within 6 months of Day 1, or ongoing requirement for systemic GvHD therapy Currently receiving or likely to require systemic immunosuppressive therapy Known active central nervous system (CNS) involvement by malignancy. Non-malignant CNS disease such as stroke, epilepsy, or neurodegenerative disease Clinically significant cardiovascular disease as defined in the protocol Known HIV infection, active Hepatitis B (HBV) or Hepatitis C (HCV) infection Donor specific antibody (DSA) to QN-019a: MFI > 2000 Other comorbid conditions and concomitant medications prohibited as per study protocol Investigator-assessed presence of any medical or social issues that are likely to interfere with study conduct or may cause increased risk to subject

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: QN-019a in Combination with Monoclonal Antibodies<br>QN-019a in Combination with Rituximab in adult subjects with r/r B-cell lymphoma. | Drug: QN-019a<br>* Experimental Interventional Therapy<br>Drug: Rituximab<br>* Monoclonal Antibody<br>Drug: Cyclophosphamid<br>* Lympho-conditioning Agent<br>Drug: Fludarabine<br>* Lympho-conditioning Agent<br>Drug: VP-16<br>* Lympho-conditioning Agent<br>|
| Experimental: QN-019a Monotherapy<br>QN-019a Monotherapy in adult subjects with r/r B-ALL | Drug: QN-019a<br>* Experimental Interventional Therapy<br>Drug: Cyclophosphamid<br>* Lympho-conditioning Agent<br>Drug: Fludarabine<br>* Lympho-conditioning Agent<br>Drug: VP-16<br>* Lympho-conditioning Agent<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The incidence of subjects with Dose Limiting Toxicities within each dose level cohort |  | Day 28 | 
| Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] | Incidence, nature, and severity of treatment related adverse events will be evaluated. | Day 28 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response rate (ORR) of QN-019a as monotherapy in r/r B-ALL and in combination with Rituximab in r/r B-cell Lymphoma |  | From baseline tumor assessment up to approximately 2 years after last dose of QN-019a | 
| Duration of response (DOR) of QN-019a as monotherapy in r/r B-ALL and in combination with Rituximab in r/r B-cell Lymphoma |  | Up to approximately 2 years after last dose of QN-019a | 
| Progression-free survival (PFS) of QN-019a in combination with Rituximab in r/r B-cell Lymphoma |  | Up to approximately 2 years after last dose of QN-019a | 
| Overall survival (OS) of QN-019a as monotherapy in r/r B-ALL and in combination with Rituximab in r/r B-cell Lymphoma |  | Up to approximately 2 years after last dose of QN-019a | 
| Determination of the pharmacokinetics (PK) of QN-019a cells in peripheral blood | The PK of QN-019a in peripheral blood will be reported as the relative percentage of product (QN-019a) DNA versus patient DNA (% chimerism) measured from blood samples at the specified time points | Up to approximately 2 years after last dose of QN-019a | 
| Event-free survival (EFS) of QN-019a as monotherapy in r/r B-ALL |  | Up to approximately 2 years after last dose of QN-019a |