Study to Assess if ABP798 is Safe & Effective in Treating Non Hodgkin Lymphoma Compared to Rituximab

Study Overview
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Brief Summary
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This was a randomized, double-blind, active-controlled, multiple-dose, clinical similarity study to evaluate the efficacy, pharmacokinetics, pharmacodynamics, safety, tolerability and immunogenicity of ABP 798 compared with rituximab in subjects with grade 1, 2, or 3a follicular B-cell NHL and low tumor burden. Subjects were randomized in a 1:1 ratio to receive a 375 mg/m^2 intravenous infusion of either ABP 798 or rituximab once weekly for 4 weeks followed by dosing at weeks 12 and 20.

Official Title
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A Randomized, Double-Blind Study Evaluating the Efficacy, Safety and Immunogenicity of ABP 798 Compared With Rituximab in Subjects With CD20 Positive B-Cell Non-Hodgkin Lymphoma (NHL)

Conditions
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Lymphoma, Non-Hodgkin

Intervention / Treatment
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* Biological: ABP 798
* Biological: Rituximab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males and females 18 years of age and older Histological confirmed (by lymph node or extranodal region biopsy), Grade 1, 2, or 3a follicular B-cell NHL expressing CD20 within 12 months before randomization Stage 2, 3, or 4 (per Cotswold's Modification of Ann Arbor Staging System) with measurable disease (per International Working Group) subjects must have a baseline scan (computed tomography [CT]) of the neck (if palpable lymph node > 1.0 cm), chest, abdomen, and pelvis to assess disease burden within 6 weeks before randomization subjects must have had a baseline bone marrow biopsy within 12 months before randomization. Previously confirmed positive bone marrow involvement does not need to be repeated for purposes of screening. Low tumor burden based on the Groupe d'Etudes des Lymphomes Folliculaires (GELF) criteria largest nodal or extranodal mass ≤ 7 cm no more than 3 nodal sites with diameter > 3 cm no splenomegaly > 16cm by CT scan and no symptomatic splenomegaly no significant pleural or peritoneal serous effusions by CT lactate dehydrogenase ≤ upper limit of normal (ULN) no B symptoms (night sweats, fever [temperature > 38°C], weight loss > 10% in the previous 6 months) Exclusion Criteria: Diffuse large cell component and/or Grade 3b follicular NHL History or known presence of central nervous system metastases Malignancy other than NHL within 5 years (except treated in-situ cervical cancer, or squamous or basal cell carcinoma of the skin) Recent infection requiring a course of systemic anti-infective agents that was completed ≤ 7 days before randomization (with the exception of uncomplicated urinary tract infection) Other investigational procedures that can impact the study data, results, or patient safety while participating in this study are excluded; participation in observational studies is allowed. Subject is currently enrolled in or has not yet completed at least 30 days or 5 half-lives (whichever is longer) since ending other investigational device or drug study(s), including vaccines, or subject is receiving other investigational agent(s) Previous use of either commercially available or investigational chemotherapy, biological, or immunological therapy for NHL (including rituximab or biosimilar rituximab, or other anti-CD20 treatments) Systemic corticosteroid use within 3 months before randomization (inhaled are allowable)

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: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ABP 798<br>ABP 798 was administered at a dose of 375 mg/m^2 as an intravenous (IV) infusion once weekly for 4 weeks followed by dosing at weeks 12 and 20. | Biological: ABP 798<br>* ABP 798 was supplied as a sterile, preservative-free liquid concentrate for IV infusion at a concentration of 10 mg/mL in either 100 mg/10 mL or 500 mg/50 mL single-dose vials. Subjects were to receive premedications before each infusion. Premedications were to be given according to local practice for administration of rituximab therapy.<br>* Other names: biosimilar to rituximab;|
| Active Comparator: Rituximab<br>Rituximab was administered at a dose of 375 mg/m^2 as an IV infusion once weekly for 4 weeks followed by dosing at weeks 12 and 20. | Biological: Rituximab<br>* Rituximab was procured from commercial supplies in the US and was supplied as a sterile, clear, colorless, preservative-free liquid concentrate for IV infusion at a concentration of 10 mg/mL in either 100-mg/10 mL or 500-mg/50 mL single-dose vials. Subjects were to receive premedications before each infusion. Premedications were to be given according to local practice for administration of rituximab therapy.<br>* Other names: Rituxan;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Who Responded (Overall Response Rate - ORR) by Week 28 Based on Independent Central Assessment of Disease | Overall response within the first treatment cycle was assessed according to International Working Group - Non-Hodgkin Lymphoma criteria (IWG-NHL criteria [Cheson et al, 1999]) by a central reader. Response was evaluated using computerized tomography (CT) scans and positron emission tomography (PET) (to assess nodal disease/organ enlargement), and bone marrow biopsy (to assess bone marrow infiltration). ORR was the percentage of participants with a best overall response of complete response (CR), unconfirmed complete response (CRu) or partial response (PR). Participants that do not meet the criteria for response were considered non-responders. CR was defined as no evidence of disease. CRu showed nodes in the original sum of the products (SPD) regressed by >75% and/or indeterminate bone marrow results. PR was a ≥ 50% decrease in SPD of the six largest dominant nodes; >=50% decrease in liver and spleen nodes, and no increase in size of other nodes nor any new sites of disease. | Post treatment up to Week 28 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Who Responded (Overall Response Rate - ORR) at Week 12 Based on Independent Central Assessment of Disease | Overall response within the first treatment cycle was assessed according to International Working Group - Non-Hodgkin Lymphoma criteria (IWG-NHL criteria [Cheson et al, 1999]) by a central reader. Response was evaluated using computerized tomography (CT) scans and positron emission tomography (PET) (to assess nodal disease/organ enlargement), and bone marrow biopsy (to assess bone marrow infiltration). ORR was the percentage of participants with a best overall response of complete response (CR), unconfirmed complete response (CRu) or partial response (PR). Participants that do not meet the criteria for response were considered non-responders. CR was defined as no evidence of disease. CRu showed nodes in the original sum of the products (SPD) regressed by >75% and/or indeterminate bone marrow results. PR was a ≥ 50% decrease in SPD of the six largest dominant nodes; >=50% decrease in liver and spleen nodes, and no increase in size of other nodes nor any new sites of disease. | Week 12 | 
| Pharmacokinetic Serum Concentrations by Visit | Pharmacokinetic serum samples were analyzed by a central lab. Lower limit of quantification (LLOQ) was 0.25 ug/mL. PK concentrations below the lower limit of quantification were assigned a value of 0. Geometric mean and geometric CV were only calculated using concentrations >0. | Weeks 2, 3, 4, 12 and 20 | 
| Percentage of Participants With Complete Depletion of Clusters of Differentiation 19-Positive (CD19+) Cell Count From Baseline to Day 8 | Complete depletion of CD19+ cell count at any postdose time was defined as CD19+ cell counts < 20 cell/μL (0.02 * 10^9 cell/L). Participants with missing CD19+ cell count at baseline or participants with CD19+ cell count < 20 cell/μL at baseline were to be excluded from the derivation of complete depletion of CD19+ cell count. | Baseline (Day 1), Study Day 8 | 
| Total Immunoglobulin G (IgG) Results by Visit | Samples were analyzed by a central lab. | Baseline (Day 1), Day 8 (Week 2), Weeks 3, 4, 28 | 
| Total Immunoglobulin M (IgM) Results by Visit | Samples were analyzed by a central lab. | Baseline (Day 1), Day 8 (Week 2), Weeks 3, 4, 28 | 
| Participants With Treatment-Emergent Adverse Events | An adverse event (AE) is defined as any untoward medical occurrence in a clinical trial participant. The event does not necessarily have a causal relationship with study treatment. Each AE was graded for severity according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4.03, where Grade 1 = Mild AE Grade 2 = Moderate AE Grade 3 = Severe AE Grade 4 = Life-threatening or disabling AE Grade 5 = Death related to AE. Serious adverse events include any event that is fatal, life threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, a congenital anomaly/birth defect, or other significant medical hazard. IP = investigational product | Day 1 (post treatment) to Week 28 | 
| Percentage of Participants With Treatment-emergent Adverse Events of Interest (AEOIs) | The AEOIs prespecified for this study were infusion reactions including hypersensitivity, cardiac disorders, serious infections, progressive multifocal leukoencephalopathy, hematological reactions, hepatitis B reactivation, opportunistic infections, severe mucocutaneous reactions, tumor lysis syndrome, gastrointestinal perforation, and reversible posterior leukoencephalopathy syndrome. Infusion reactions including hypersensitivity adverse events of interest must have start date the same as, or one day after, an investigational product administration start date. | Day 1 (post treatment) to Week 28 | 
| Number of Participants Who Developed Anti-drug Antibodies | Samples were first tested in an electrochemiluminescence (ECL)-based bridging immunoassay to detect antibodies capable of binding to ABP 798/rituximab (Binding Antibody Assay). Samples confirmed to be positive for binding antibodies were subsequently tested in a cell-based assay to determine neutralizing activity against ABP 798/rituximab (Neutralizing Antibody Assay). Developing antibody incidence was defined as participants with a negative or no binding antibody result at baseline and a positive antibody result at any post-baseline time point. | Baseline (Day 1), Weeks 12, 20 and 28 | 
| Participants' Progression-Free Survival (PFS) Status Based on the Independent Central Assessment of Disease | PFS was based on disease assessments determined by the central, independent, blinded radiologists' and oncologist's review. | Day 1 up to Week 28 | 
| Percentage of Participants Who Survived -- Overall Survival (OS) | Percentage of participants who were alive at the end of the study. | Day 1 up to Week 28 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CD20 Positive B-cell Non-Hodgkin Lymphoma, ABP 798