CLBR001 and SWI019 in Patients With Relapsed / Refractory B-cell Malignancies

Phase 1

Completed

• Conditions: Diffuse Large B Cell Lymphoma (DLBCL); Burkitt Lymphoma; Follicular Lymphoma (FL); Marginal Zone Lymphoma (MZL); Transformed Follicular Lymphoma; Waldenstrom Macroglobulinemia; Relapsed/Refractory B-cell Lymphomas; Chronic Lymphocytic Leukemia (CLL); Mantle Cell Lymphoma; Primary Mediastinal Large B Cell Lymphoma
• Interventions: Combination Product: CLBR001 and SWI019

• Registration Number: NCT04450069
• Lead Sponsor: Calibr, a division of Scripps Research

Brief Summary

CLBR001 + SWI019 is an combination investigational immunotherapy being evaluated as a potential treatment for patients diagnosed with B cell malignancies who are refractory or unresponsive to salvage therapy or who cannot be considered for or have progressed after autologous hematopoietic cell transplantation. This first-in-human study will assess the safety and tolerability of CLBR001 + SWI019 and is designed to determine the maximum tolerated dose (MTD) or optimal SWI019 dose (OSD). Patients will be administered a single infusion of CLBR001 cells followed by cycles of SWI019. The study will also assess the pharmacokinetics and pharmacodynamics of CLBR001 + SWI019.

Detailed Description

CLBR001 + SWI019 is a two-component therapy comprising an autologous chimeric antigen receptor T (CAR-T) cell product (CLBR001, the switchable CAR-T cell (sCAR-T)) and an anti-CD19 (cluster of differentiation antigen 19) antibody (SWI019, the switch, a biologic). In combination, SWI019 acts as an adapter molecule that controls the activity of the CLBR001 CAR-T cell product.

Study Timeline

• Study First Submitted: 2020-06-23
• Study First Submitted QC: 2020-06-25
• Study First Posted: 2020-06-29
• Study Start: 2020-08-14
• Primary Completion: 2024-05-06
• Study Completion: 2024-05-06
• Status Verified: 2024-08
• Last Update Submitted: 2024-08-19
• Last Update Posted: 2024-08-20

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 18

Inclusion Criteria

• Patients with relapsed / refractory previously treated B cell malignancies (according to the World Health Organization classification; 2017)
• Patients must have received adequate prior therapy including at least two lines of prior therapies including anthracycline or bendamustine-containing chemotherapy, anti-CD20 (cluster of differentiation antigen 20) therapies and/or Brutton's tyrosine kinase (BTK) inhibitors
• Patients treated with prior CD19 targeted molecules (e.g., Blincyto) must have confirmed CD19+ disease
• Patients must be ineligible for allogeneic stem cell transplant (SCT)
• Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0 or 1
• Estimated life expectancy of ≥ 12 weeks from the first day of SWI019 dose administered
• Willing to undergo pre- and post-treatment core needle biopsy
• Adequate hematological, renal, pulmonary, cardiac, and liver function
• Resolved adverse events of any prior therapy to either baseline or CTCAE Grade ≤1
• Women of childbearing potential, a negative pregnancy test and must agree to practice effective birth control
• Men sexually active with female partners of child bearing potential must agree to practice effective contraception
• Willing and able to comply with scheduled visits, treatment plan, laboratory tests and other procedures

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Exclusion Criteria

• Patients diagnosed with certain disease histologies including pediatric lymphomas/leukemias, monoclonal gammopathy of undetermined significance (MGUS), T-cell histiocyte large B cell lymphoma
• Pregnant or lactating women
• Active bacterial, viral, and fungal infections
• History of allogeneic stem cell transplantation
• Treatment with any prior lentiviral or retroviral based CAR-T
• Patients receiving live (attenuated) vaccines within 4 weeks of screening visit or need for live vaccine on study
• Patients with known active central nervous system (CNS) disease. Patients with prior CNS disease that has been effectively treated may be eligible
• History of Class III or IV New York Heart Association (NYHA) heart failure, myocardial infarction, unstable angina or other significant cardiac disease within 6 months of screening
• Involvement of cardiac tissue by lymphoma
• Uncontrolled autoimmune hemolytic anemia or idiopathic thrombocytopenic purpura (ITP)
• HIV-1 and HIV-2 antibody positive patients

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Dose Escalation	CLBR001 and SWI019	CLBR001 + SWI019 is administered via infusion with ascending dose levels to determine the maximum tolerated dose (MTD) or optimal SWI019 dose (OSD)

Primary Outcome Measures

Name	Time	Method
Frequency, relatedness, severity and duration of treatment emergent and treatment related adverse events	35 days	To determine the frequency, relatedness, severity and duration of treatment emergent and treatment related adverse events
Number of first cycle dose limiting toxicities (DLT) as assessed by Common Terminology Criteria for Adverse Events (CTCAE)	up to 1 year	Based on the number of first cycle dose limiting toxicities (DLT) as assessed by CTCAE to determine maximum tolerated dose (MTD)

Secondary Outcome Measures

Name	Time	Method
Area under the curve (AUC) of SWI019	up to Day 35	To quantify the cumulative amount of SWI019 in a patient's peripheral blood over time
Maximum drug concentration (Cmax) of SWI019	up to Day 35	To determine the maximum concentration of SWI019 in a patient's peripheral blood
Time to reach Cmax (Tmax) of SWI019	up to Day 35	To identify the time point when the concentration of SWI019 reaches maximum in a patient's peripheral blood
Clearance (CL) of SWI019	up to Day 35	To determine the clearance factor of SWI019 in a patient's peripheral blood
Quantification of CLBR001 cells in peripheral blood	up to 1 year	To quantify CLBR001 in a patient's peripheral blood at different time points
Immunogenic response to CLBR001	up to 1 year	To evaluate the anti-drug antibodies in response to CLBR001 administration in a patient's peripheral blood
Overall survival (OS)	up to 1 year	To evaluate the overall duration of patient's survival
Immunogenic response to SWI019	up to 1 year	To evaluate the anti-drug antibodies in response to SWI019 administration in a patient's peripheral blood
Apparent elimination half-life (t1/2) of SWI019	up to Day 35	To identify the time point when the concentration of SWI019 reaches half of maximum in a patient's peripheral blood
Phenotype of CLBR001 in peripheral blood and/or tumor/bone marrow biopsies	up to 1 year	To evaluate the phenotype of CLBR001 in a patient's peripheral blood at different time points by flow cytometry
Serum cytokine concentrations	up to 1 year	To measure the cytokine levels (e.g. TNFa, IL-6, IL-1, IL-2, etc.) in a patient's peripheral blood at different time points
Overall (best) objective response by the Response Evaluation Criteria in Lymphoma (RECIL) and Lugano criteria	up to 1 year	To determine the overall (best) objective anti-cancer response by RECIL and Lugano criteria
Duration of response (DOR)	up to 1 year	To evaluate the duration of anti-cancer response after CLBR001 and SWI019 administration
Progression free survival (PFS)	up to 1 year	To evaluate the duration of patient's progression-free survival

Trial Locations

Locations (8)

University of California at San Diego; 🇺🇸 San Diego, California, United States

Masonic Cancer Center, University of Minnesota; 🇺🇸 Minneapolis, Minnesota, United States

Sarah Cannon Research Institute - Texas Transplant Institute; 🇺🇸 San Antonio, Texas, United States

Wake Forest Baptist Health; 🇺🇸 Winston-Salem, North Carolina, United States

Sarah Cannon Research Institute - Tennessee Oncology; 🇺🇸 Nashville, Tennessee, United States

Weill Cornell Medical College - New York Presbyterian Hospital; 🇺🇸 New York, New York, United States

City of Hope National Medical Center; 🇺🇸 Duarte, California, United States

University of Chicago; 🇺🇸 Chicago, Illinois, United States