Evaluate the Efficacy and Safety of HLX01 Versus Mabthera in Patients With Low Tumour Burden Follicular Lymphoma.

Study Overview
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Brief Summary
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The study is a Phase 3 multi-centre, randomised, double-blind, parallel-arm study to evaluate the efficacy and safety of HLX01 versus European Union (EU)-sourced Mabthera® as first line treatment in patients with low tumour burden FL. The study will consist of a Screening Period (up to 42 days), Treatment Period (Week 1 to Week 44/Month 11), and End of Study (EOS; Month 12 Visit). Approximately 212 patients (106 in each treatment group) will be enrolled. Utilising a 1-sided 97.5% CI for the risk difference, a reference proportion of 83.2% for Mabthera®, delta for non-inferiority of -17%, and assuming a true difference of 1%, a sample size of 106 patients per arm (212 total) provides approximately 85% power to show non-inferiority of HLX01 to Mabthera® on a primary endpoint of risk difference in ORR up to Week 28. No dropout is included, as all patients will either have data provided for ORR (based on best response), or will be classed as non-responder.

Official Title
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A Phase 3 Multi-Centre, Randomised, Double-Blind, Parallel-Arm Study to Evaluate the Efficacy and Safety of HLX01 Versus Rituximab (Mabthera®) as First Line Treatment in Patients With Low Tumour Burden Follicular Lymphoma.

Conditions
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CD20-positive Follicular Lymphoma, With Low Tumour Burden

Intervention / Treatment
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* Drug: HLX01
* Drug: Mabthera®


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Voluntary written informed consent before any study-related activities ≥ 18 years of age Histologically-confirmed, stage II to IV NHL (CD20+ FL of grades 1, 2, or 3a) by World Health Organization classification of lymphoid neoplasms (2016 revision) [11] Low tumour burden according to the GELF criteria The Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 Availability of tumour sample within 12 months before start of study drug treatment At least 1 bi-dimensionally measurable nodal lesion >1.5 cm or extranodal lesion >1 cm in its longest diameter by CT scan as defined by the Modified Lugano Response Classification 2014 Adequate organ function Exclusion Criteria: Prior treatment for FL. Patients previously treated with radiotherapy for stage I FL may be eligible provided they have a measurable lesion located outside the radiation field Transformation to high-grade lymphoma Patients with advanced disease that are considered for treatment with combined chemo immunotherapy Presence or history of central nervous system (CNS) lymphoma involvement Treatment with an investigational agent within 28 days of the first dose of study drug infusion Prior treatment with a chimeric antibody, including HLX01 and Mabthera® History of another malignancy within 2 years of screening, with the exception of curatively treated non-melanoma skin cancer, carcinoma in situ of the uterine cervix, breast or bladder, localised prostate cancer stage T1c or less - and provided that the patient remains relapse free Major surgery within 28 days of the first dose of study drug infusion (excluding lymph node biopsy) Known human immunodeficiency virus (HIV) infection (Serological test for HIV should be performed at screen unless prohibited by local regulations) Active and/or severe infections, including any ongoing infection requiring IV anti microbial treatment Have a current diagnosis of active tuberculosis Active HBV and a positive serological test for HBV (except seropositive due to HBV vaccination) or hepatitis C virus (HCV) Ongoing immunosuppressant treatment; corticosteroid treatment exceeding 20 mg/day prednisone or equivalent within 7 days of the first dose of study drug infusion Known hypersensitivity or allergy to the active principle and/or formulations' ingredients; history of severe allergy or anaphylaxis to murine or biologic agents Live or live attenuated vaccine within 28 days of the first dose of study drug infusion History of significant cardiac or vascular disease including, but not limited to: history of stroke, unstable angina, myocardial infarction or ventricular arrhythmia requiring medication or mechanical control within 6 months before randomisation; congestive heart failure according to the New York Heart Association (NYHA) Functional Classification class III or IV

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: HLX01<br> | Drug: HLX01<br>* Patients will receive HLX01 intravenous (IV) infusion once a week for 4 weeks induction treatment (on Days 1, 8, 15, and 22), and then continue to receive maintenance treatment at Weeks 12, 20, 28, 36, and 44.<br>|
| Active Comparator: EU-sourced rituximab (Mabthera®)<br> | Drug: Mabthera®<br>* Patients will receive Mabthera® intravenous (IV) infusion once a week for 4 weeks induction treatment (on Days 1, 8, 15, and 22), and then continue to receive maintenance treatment at Weeks 12, 20, 28, 36, and 44.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Response Rate | Overall Response Rate up to Week 28, defined as the proportion of patients achieving either complete response (CR) or PR as best response from the first dose of study drug through Week 28 as assessed by a blinded independent review committee according to the Modified Lugano Response Classification 2014. | rom the first dose of study drug through Week 28 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AEs | adverse events | up to 12 months | 
| SAEs | serious adverse events | up to 12 months | 
| Immunogenicity | ADA and neutralising antibody | up to 12 months | 
| Time-to-progression of disease (TTPD) | Time-to-progression of disease | up to 12 months | 
| PFS | progression-free survival | up to 12 months | 
| Cmax | max blood cocentration | up to 12 months | 
| Ctrough | trough serum concentration after each dose during induction period and selected doses thereafter | up to 12 months |