Compare Efficacy, Safety, and Immunogenicity of Proposed Rituximab Biosimilar (DRL_RI) With MabThera® in LTB Follicular Lymphoma

A Double-blind, Parallel-group, Phase III Study to Compare the Efficacy, Safety, and Immunogenicity of Proposed Rituximab Biosimilar (DRL_RI) With MabThera® in Subjects With Previously Untreated (CD)20-Positive LTB Follicular Lymphoma

The primary objective of the current study is to demonstrate the equivalent efficacy of rituximab (DRL_RI) and MabThera® in subjects with Low Tumor Burden Follicular Lymphoma (LTB-FL).

Also evaluated by Pharmacokinetic, safety, and immunogenicity assessment between a proposed biosimilar (DRL_RI) and the RMP, as an component of clinical study program, and collectively providing the evidence of biosimilarity.

The study will compare the safety and efficacy of DRL_RI vs MabThera in patients with Low Tumor Burden Follicular Lymphoma (LTB-FL). The primary objective is to establish comparative efficacy as measured by ORR up to week 28

It is planned to randomise approx. 312 subjects at approximately ≥ 130 study sites worldwide. Subjects with LTB-FL will be randomized to receive either DRL_RI or MabThera®. Till date, 68 patients have been randomized for the study.

The study specific objectives are mentioned below:

Primary Objective:

• To demonstrate the equivalent efficacy of DRL_RI (biosimilar rituximab) and MabThera in subjects with CD20-positive, LTB FL, as measured by overall response rate (ORR) up to Week 28 evaluated in accordance with Cheson, 1999 response criteria for Non-Hodgkin's Lymphomas.

Secondary Objectives:

• To compare the progression-free survival (PFS), overall survival (OS), and duration of response (DOR) of DRL_RI with MabThera® in subjects with CD20-positive, LTB FL.
• To compare the safety, tolerability, and immunogenicity of DRL_RI with MabThera in subjects with CD20-positive, LTB-FL.

Exploratory Objectives

• To explore the pharmacokinetic (PK) parameters of DRL_RI and MabThera, using a population-PK modelling approach.
• To explore the pharmacodynamic parameters of DRL_RI and MabThera.

Inclusion Criteria:

1. Subject is Male or female subjects aged ≥18 years of age.

2. Subject is histologically confirmed, Grade 1-3a, previous ly untreated, CD20-pos itive.

3. Subject has Ann Arbor Stage II to IV and ECOG status of 0 to 1.

4. Subject has Low tumor burden follicular lymphoma as per Groupe d'Etude des Lymphomes Folliculaires (GELF) Criteria

5. Subject has at least 1 measurable tumor mass in 2 dimensions, and the mass must be:

   1. Nodal lesion >15 mm in the longest dimension; or
   2. Noda l lesion >10 mm to he longest dimension; dimens ion and >10 mm in the shortest dimension; or
   3. Extra-nodal lesion with both long and short dimensions ≥10 mm.

6. Subject has Life expectancy ≥3 months.

7. If female subject, then subject should be non-pregnant, non-lactating.

Exclusion Criteria:

1. Subject with prior use of rituximab or any CD20 monoclonal antibody for any reason.
2. Subjects with known hypersensitivity to rituximab or its excipients, or to proteins of murine or other foreign origin.
3. Any prior therapy for follicular lymphoma (including but not limited to chemotherapy, radiotherapy) or subjects on chronic supra-substitutive doses of systemic gluco-corticosteriods.
4. Subjects who, in the opinion of the Investigator, require additional concomitant treatment for lymphoma.
5. Evidence of histologic transformation to high grade lymphoma or diffuse large B-cell lymphoma.
6. Subjects with known sero-positivity for or history of active viral infection with human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg) will be excluded. And if positive for hepatitis B core antibody or hepatitis C virus (HCV) antibody can only be enrolled if HBV - DNA level <20 IU/mL (or 112 copies/mL) and HCV - RNA is negative respectively by PCR test..
7. Subjects who have received a live vaccine within last 3 months of the first administration of study drug.
8. Subjects with history or presence of a medical condition or disease that in the Investigator's opinion would place the subject at an unacceptable risk for study participation.
9. Participation in any clinical study or having taken any investigational therapy (within 2-months of the first dose of study drug.
10. Women of childbearing potential who do not consent to use highly effective methods of birth control.