Dose De-escalation Study of the PI3k Alpha/Delta Inhibitor Copanlisib Given in Combination With the Immunotherapeutic Agents Nivolumab and Rituximab in Patients With Relapsed/Refractory Indolent Lymphoma
Patients with relapsed or refractory follicular or marginal zone lymphoma who have received
at least one prior line of therapy will receive
Copanlisib IV: day 1, 8, 15 every 28 days
Nivolumab IV: Cycle 1 days 1 and 15; then day 1 only
Rituximab IV: Cycle 1 days 1, 8, 15, 22; then day 1 (C2-6); then Q2 cycles (8-12)
Patients with relapsed/refractory lymphoma generally have few if any curative options and
demonstrate poor response rates to standard salvage therapies. Novel regimens utilizing
molecular targets are needed to improve outcomes in this patient population. While studies
evaluating single agent small-molecule inhibitors have demonstrated activity in this setting,
combinations of these drugs are generally thought to be more efficacious due to targeting
separate mechanisms of action and decreased chance of developing resistance. The PD-1/PD-L1
axis is a molecular target that has been demonstrated to be up-regulated in several tumors
including malignant lymphoma. Several pre-clinical studies have demonstrated the importance
of this axis on clinical outcomes of patients afflicted with low grade lymphoma including FL.
Targeting this axis with specific inhibitors would appear to be a rationale way to improve
outcomes in patients afflicted with these diseases. PI3K inhibitors in addition to inhibiting
signaling, impart changes in the immune cells in the tumor microenvironment and would appear
to be a logical candidate to explore in combination with immunotherapy. Based on these
preliminary data, we believe that we have justification for proceeding with our proposed
phase I study to combine the PD-1 inhibitor, nivolumab, with the PI3K inhibitor, copanlisib,
and the CD20 antibody, rituximab, in patients with relapsed/refractory follicular and
marginal zone lymphoma. This work has the potential to provide a novel strategy to improve
upon the clinical response noted in this patient population.
If you are confirmed eligible after full screening, you will be required to understand and sign the informed consent if you decide to enroll in the study. Once enrolled you may be asked to make scheduled visits over a period of time.
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