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

Description

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