Abstract CT290: Ibrutinib-rituximab versus placebo-rituximab for first-line treatment of follicular lymphoma: PERSPECTIVE, a randomized phase 3 study

Abstract

Abstract Background: First-line chemotherapy-free treatment options are limited for patients with follicular lymphoma (FL) who are elderly or have comorbid conditions. Rituximab has been used in the clinic in the first-line setting as a single-agent for the treatment of elderly, frail patients or those with low tumor burden. Ibrutinib is a once-daily Bruton's tyrosine kinase inhibitor approved in the US for the treatment of various B-cell malignancies. A combination of once-daily ibrutinib and 4 weekly doses of intravenous rituximab was recently evaluated in a phase 2 study. Ibrutinib treatment was continued until disease progression or unacceptable toxicity. At a median follow-up of 34 months, the overall response rate of 85% and a complete response of 40% were noted. At 30 months, the progression-free survival (PFS) and overall survival rates were 67% and 97%, respectively (Fowler et al, BJH In Press). Based on these promising results, the ibrutinib-rituximab combination therapy was further investigated in the phase 3 PERSPECTIVE study. The two underlying aims of the study include (1) comparison of PFS outcomes with ibrutinib-rituximab and placebo-rituximab, and (2) evaluation of the differences in PFS outcomes between continuous versus fixed-duration ibrutinib. Methods: PERSPECTIVE (NCT02947347; PCYC-1141-CA), an ongoing multicenter, randomized, double-blind, placebo-controlled phase 3 study, will recruit approximately 440 previously untreated patients with FL. Patients who meet at least one Groupe d'Etude des Lymphomes Folliculaires criterion (Solal-Céligny et al, NEJM 1993) will be enrolled in the trial. In addition, eligible patients will also be ≥70 years or 60-69 years and have one or more of the following comorbidities: creatinine clearance 30-59 mL/min or ECOG performance status of 2. Patients who have received any prior treatment for FL or show evidence of CNS involvement or transformed lymphoma will be excluded. In Part 1 of the study, eligible patients will be randomized into two treatment arms. Patients in Arm A will receive once-daily oral ibrutinib in combination with rituximab. Patients in Arm B will receive oral placebo in combination with rituximab. In both Arms A and B, patients will be treated with weekly doses of rituximab for 4 weeks, followed by maintenance therapy with rituximab. Part 2 of the study will further evaluate patients on the ibrutinib-rituximab combination arm (Arm A), who were on ibrutinib for at least 2 years. These patients will be randomized again into two arms. Patients in the treatment arm will be receive once-daily oral ibrutinib and those in the placebo arm will be switched from ibrutinib to once-daily oral placebo. The primary endpoint for both parts of the study will be PFS. The study is currently enrolling patients and includes participating sites in the US, Europe, and Asia-Pacific Citation Format: Nathan Fowler, Ian W. Flinn, Simon Rule, Robert Chen, Long Kwei, Alvina D. Chu, Leo Gordon. Ibrutinib-rituximab versus placebo-rituximab for first-line treatment of follicular lymphoma: PERSPECTIVE, a randomized phase 3 study [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr CT290.