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

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

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.

Study Overview

• Status: Recruiting
• Conditions: B-cell Lymphoma; B-cell Acute Lymphoblastic Leukemia
• Intervention / Treatment: Drug: Rituximab; Drug: Cyclophosphamid; Drug: Fludarabine; Drug: VP-16; Drug: QN-019a

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Anticipated): 24
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310003
      • Recruiting
      • The first affiliated hospital of medical college of zhejiang university

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Zhejiang University
• Collaborators: Hangzhou Qihan Biotech Co.,Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): November 4, 2021
• Primary Completion (Anticipated): June 1, 2024
• Study Completion (Anticipated): December 1, 2024

Study Registration Dates

• First Submitted: May 13, 2022
• First Submitted That Met QC Criteria: May 17, 2022
• First Posted (Actual): May 18, 2022

Study Record Updates

• Last Update Posted (Actual): May 18, 2022
• Last Update Submitted That Met QC Criteria: May 17, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Leukemia, Lymphoid; Leukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Antineoplastic Agents, Immunological; Cyclophosphamide; Rituximab; Fludarabine
• Other Study ID Numbers: NK-002 (QN-019a)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No