NCT04431635

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

Phase IB 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.Big Ten Cancer Research Consortium BTCRC-LYM17-145

• Status: Terminated
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 6 (actual)
• Sponsor: University of Michigan Rogel Cancer Center · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

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)

Detailed description

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.

Conditions

• Indolent Lymphoma

Interventions

Type	Name	Description
DRUG	Copanlisib	Copanlisib IV: day 1, 8, 15 every 28 days
DRUG	Nivolumab	Nivolumab IV: Cycle 1 days 1 and 15; then day 1 only
DRUG	Rituximab	Rituximab IV: Cycle 1 days 1, 8, 15, 22; then day 1 (C2-6); then Q2 cycles (8-12)

Timeline

• Start date: 2020-06-15
• Primary completion: 2023-11-14
• Completion: 2023-11-14
• First posted: 2020-06-16
• Last updated: 2024-09-27

Locations

5 sites across 1 country: United States

Regulatory

• FDA-regulated drug study