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

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Background: Follicular lymphoma (FL) is the most common indolent non-Hodgkin s lymphoma (NHL) with a highly variable clinical course across patients Standard frontline therapy for FL includes a monoclonal anti-CD20 antibody with or without chemotherapy that can induce durable remissions but is gener...

Background: Follicular lymphoma (FL) is the most common indolent non-Hodgkin s lymphoma (NHL) with a highly variable clinical course across patients Standard frontline therapy for FL includes a monoclonal anti-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 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 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 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

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