Response-Adapted Therapy With Copanlisib and Rituximab in Untreated Follicular Lymphoma

Background: * Follicular lymphoma (FL) is the most common indolent non-Hodgkins lymphoma (NHL) with a highly variable clinical course across patients * Standard frontline therapy for FL includes a monoclonal anti-cluster of differentiation 20 (CD20) antibody with or without chemotherapy that can induce durable remissions but is generally not curable * The 20% of patients who relapse within 2 years of frontline chemotherapy have an inferior overall survival; molecular profiles and gene-expression signatures can identify patients at high-risk of early treatment failure but are incomplete and require further validation * The phosphoinositide 3-kinase (PI3K) pathway is critically important in FL; agents that target PI3K show good clinical activity in patients who relapse early after chemotherapy * Copanlisib is an intravenous therapy targeting both PI3K-alpha and PI3K-delta isoforms and is Food and Drug Administration (FDA)-approved for use in adults with relapsed and refractory FL * Induction therapy with copanlisib and rituximab may produce deep and durable remissions in patients with FL without the use of cytotoxic agents * Circulating tumor deoxyribonucleic acid (DNA) circulating tumor DNA (ctDNA) is a promising modality for monitoring therapy Objective: \- To determine the complete response (CR) rate after copanlisib and rituximab as induction therapy for patients with untreated follicular lymphoma Eligibility: * Patients with histologically confirmed stage II-IV follicular lymphoma, grade 1-2 or 3a that meet criteria for initiation of systemic therapy * No previous systemic therapy; prior local radiation permitted * Eastern Cooperative Oncology Group (ECOG) performance status 0-2 * Adequate bone marrow and organ function Design: * Phase 2 study of up to 65 patients with untreated FL who meet standard criteria for treatment * Patients will first be treated with a window of copanlisib monotherapy, followed by induction therapy with copanlisib and rituximab for up to 6 cycles * Patients who achieve a CR after 6 cycles of induction therapy will stop treatment and be monitored with computed tomography (CT) scans and plasma assays for circulating tumor DNA (ctDNA). Patients who relapse \> 6 months from the end of induction can be re-treated with 6 additional cycles of copanlisib and rituximab * Patients who achieve a partial response after 6 cycles of induction therapy will receive an additional 6 cycles of extended induction therapy with copanlisib and rituximab * Patients who do not achieve at least a partial response after 6 cycles of induction therapy will stop treatment and be monitored with CT scans and peripheral blood assays for ctDNA * Patients who progress or relapse after induction therapy and meet criteria for salvage therapy will be treated with standard chemotherapy and a monoclonal anti-CD20 antibody