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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
6
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)
University of Illinois Cancer Center
Chicago, Illinois, United States
University of Michigan Comprehensive Cancer Center
Ann Arbor, Michigan, United States
University of Michigan Health System
Ann Arbor, Michigan, United States
University of Nebraska Medical Center
Omaha, Nebraska, United States
Rutgers Cancer Institute of New Jersey
New Brunswick, New Jersey, United States
MTD (Maximum Tolerated Dose) of copanlisib given in combination with nivolumab and rituximab
To estimate the MTD (Maximum Tolerated Dose) of copanlisib given in combination with nivolumab and rituximab
Time frame: 28 days
Complete Response rate of the combination of copanlisib, nivolumab, and rituximab given at the MTD.
To estimate the Complete Response (CR) rate of the combination of copanlisib, nivolumab, and rituximab given at the MTD as determined by Lyric criteria \[Cheson 2016}
Time frame: 1 year
Summarize Adverse Events
Summarize all adverse events graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0
Time frame: Up to two years
Overall Response
The rate of overall response, defined as either CR or PR within 1 year of initiation of therapy.
Time frame: 1 year
Duration of Response
3\. Duration of response, as calculated from the time of initial response (CR or PR, determined by Lyric criteria \[Cheson 2016\]) until disease progression or death due to any cause (whichever occurs first).
Time frame: Up to two years
Progression Free Survival
4\. Progression free survival, as calculated from the first dose of the combination to the occurrence of definitive disease progression (as defined by Cheson 2016) or death from any cause, whichever comes first.
Time frame: Up to two years
Time to Next Treatment
Time to next treatment (TTNT) is defined as the time from end of primary treatment to institution of next therapy.
Time frame: Up to two years
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