PHASE 3 STUDY OF IBRUTINIB IN COMBINATION WITH RITUXIMAB VERSUS PLACEBO IN COMBINATION WITH RITUXIMAB IN PATIENTS WITH TREATMENT‐NAÏVE FOLLICULAR LYMPHOMA (PERSPECTIVE)

Introduction: Follicular lymphoma (FL) is the most common subtype of indolent non-Hodgkin lymphoma and has a limited number of chemotherapy-free options for treatment-naïve (TN) patients who are older or who have comorbidities. Ibrutinib, a first-in-class, once-daily inhibitor of Bruton's tyrosine kinase, is approved in the EU for the treatment of various B-cell malignancies. In a phase 2 study, frontline treatment with ibrutinib in combination with rituximab (4 weekly doses without maintenance) demonstrated an overall response rate of 85% (35% complete response) with a median follow-up of 22 months and an 18-month PFS rate of 87% (Fowler, Blood 2016). PERSPECTIVE (PCYC-1141, NCT02947347), a randomized, double-blind, placebo-controlled phase 3 trial that builds on the phase 2 study, will be conducted in two parts and will evaluate (1) whether frontline treatment with ibrutinib in combination with rituximab results in prolongation of PFS compared with rituximab alone and (2) whether continuous treatment with ibrutinib affects PFS outcomes compared to finite treatment. Methods: Approximately 440 patients with TN FL will be randomized to receive either ibrutinib or oral placebo once daily; all patients will be administered 4 weekly doses of rituximab followed by maintenance. After at least 2 years of treatment during Part 1, patients randomized to ibrutinib who remain on ibrutinib will be re-randomized in Part 2 to either continue ibrutinib or switch to placebo. Patients must meet at least one Groupe d'Etude des Lymphomes Folliculaires (GELF) criterion and be at least ≥70 years of age or between ages 60 to 69 with one or more comorbidities (creatinine clearance 30–59 mL/min or ECOG performance status of 2). Key exclusion criteria include any prior treatment for FL, evidence of central nervous system involvement, or transformation. Analyses will be conducted in two distinct parts, both with a primary endpoint of PFS. The study is currently in progress with sites planned in the US, EU, and Asia Pacific. Keywords: follicular lymphoma (FL); ibrutinib; rituximab.