A Phase III Trial Comparing Tisagenlecleucel to Standard of Care (SoC) in Adult Participants With r/r Follicular Lymphoma

The purpose of this phase III study is to verify the clinical benefit of tisagenlecleucel for the treatment of r/r FL by comparing the tisagenlecleucel treatment strategy to standard of care therapy in patients with r/r FL after two or more lines of systemic therapy, with progression-free survival (PFS) as the primary endpoint.

The primary objective is to demonstrate superiority of the tisagenlecleucel treatment strategy over standard of care (SOC) therapy with respect to progression-free survival (PFS) determined by blinded independent review committee (BIRC) based on the Lugano response criteria.

Participants randomized to Arm A (tisagenlecleucel treatment) will receive a single infusion of 0.6 to 6 x 10^8 CAR-positive viable T-cells.

Participants randomized to Arm B (Standard of Care) will receive R2 or R-CHOP based on investigator choice and this has to be determined prior to randomization.

Inclusion criteria

• Age ≥ 18 years at the date of signing the informed consent form.
• Follicular lymphoma grade 1, 2, or 3A confirmed histologically after latest relapse (local assessment).
• Relapsed or refractory disease after a second or later line of systemic therapy including an anti-CD20 antibody and an alkylating agent.
• Disease that is both active on Positron emission tomography (PET) scan (defined as a score of 4 or 5 on the Deauville 5-point scale) and measurable on Computed tomography (CT) scan.
• ECOG performance status of 0, 1 or 2 at screening.
• Adequate hematologic, renal, hepatic and pulmonary organ function at screening.
• Must meet the institutional criteria to undergo leukapheresis (unless historical leukapheresis is available).
• Must be eligible for treatment with the selected standard of care regimen.

Exclusion criteria

• Follicular lymphoma grade 3B or evidence of histologic transformation.
• Prior treatment with anti-CD19 therapy, gene therapy, or adoptive T-cell therapy.
• Active CNS involvement by malignancy.
• Clinically significant active infection, presence of Human immunodeficiency virus (HIV) antibody or active hepatitis B or C.
• Active neurological autoimmune or inflammatory disorders (e.g., Guillain-Barré syndrome).
• Investigational medicinal product within the last 30 days or five half-lives (whichever is longer) prior to randomization.
• Clinically significant cardiovascular conditions such as acute coronary syndrome, significant cardiac arrhythmias, heart failure or decreased LVEF.

Other protocol defined inclusion/exclusion criteria may apply