Ignite Creation Date:
2025-12-25 @ 2:44 AM
Ignite Modification Date:
2026-01-01 @ 6:21 AM
Study NCT ID:
NCT03502733
Status:
ACTIVE_NOT_RECRUITING
Last Update Posted:
2025-12-24
First Post:
2018-04-17
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Testing the Combination of Copanlisib, Nivolumab and Ipilimumab in Patients With Advanced Cancer and Lymphoma
Sponsor:
National Cancer Institute (NCI)
Organization:
Study Overview
Official Title:
Phase Ib Study of Copanlisib in Combination With Nivolumab or With Nivolumab and Ipilimumab
Status:
ACTIVE_NOT_RECRUITING
Status Verified Date:
2025-12
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This phase Ib trial studies the side effects and best dose of copanlisib and nivolumab and side effects of copanlisib given together with nivolumab and ipilimumab in treating patients with solid tumors that may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced) or lymphoma. Copanlisib stops tumors from growing by blocking proteins that are known to be important for tumor cell growth. Immunotherapy with monoclonal antibodies, such as nivolumab and ipilimumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving copanlisib together with nivolumab or with nivolumab and ipilimumab may work better in treating patients with solid tumors or lymphoma.
Detailed Description:
PRIMARY OBJECTIVES:
I. To establish the safety, tolerability, and the recommended phase 2 dose (RP2D) of copanlisib and nivolumab combination in patients with advanced solid tumors and lymphomas.
II. To evaluate the safety and tolerability of copanlisib combined with nivolumab and ipilimumab in patients with advanced solid tumors and lymphomas.
EXPLORATORY OBJECTIVES:
I. Evaluate the effect of the doublet and triplet combinations on markers of anti-tumor immunity in circulating immune cells and pre- and post-treatment tumor biopsies.
II. Evaluate the effect of the combinations on biomarkers of AKT inhibition, deoxyribonucleic acid (DNA) damage (gammaH2AX, pNbs1, Rad51), apoptosis, and epithelial-mesenchymal transition in pre- and post- treatment tumor biopsies.
III. Assess preliminary antitumor activity of the combinations.
OUTLINE: This is a dose-escalation study of copanlisib and nivolumab, followed by a dose-expansion study.
COHORT I (DOUBLET TREATMENT PLAN): Patients receive copanlisib intravenously (IV) over 1 hour on days 1 and 15 or days 1, 8, and 15 of each cycle and nivolumab IV over 30 minutes on day 1 or days 1 and 15 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo computed tomography (CT) scan and/or magnetic resonance imaging (MRI) throughout the trial. Patients undergo blood sample collection on study and during follow-up, as well as tumor biopsy on study. Patients also undergo an echocardiography (ECHO) during screening and as clinically indicated on study.
COHORT II (TRIPLET SAFETY RUN-IN PHASE TREATMENT PLAN): Patients receive copanlisib IV over 1 hour on days 1, 8, and 15 of each cycle, nivolumab IV over 30 minutes on day 1 of each cycle, and ipilimumab IV over 90 minutes on day 1 for cycles 1-4. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT scan and/or MRI throughout the trial. Patients undergo an ECHO during screening and as clinically indicated on study.
COHORT III (TRIPLET TREATMENT PLAN): Patients receive copanlisib IV over 1 hour on days 1, 8, and 15 of each cycle, nivolumab IV over 30 minutes on day 15 of cycle 1 and then day 1 of each subsequent cycles, and ipilimumab IV over 90 minutes on day 1 for cycles 2-5. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT scan and/or MRI throughout the trial. Patients undergo blood sample collection on study and during follow-up, as well as tumor biopsy on study. Patients also undergo an ECHO during screening and as clinically indicated on study.
After completion of study treatment, patients are followed up monthly for 4 months.
I. To establish the safety, tolerability, and the recommended phase 2 dose (RP2D) of copanlisib and nivolumab combination in patients with advanced solid tumors and lymphomas.
II. To evaluate the safety and tolerability of copanlisib combined with nivolumab and ipilimumab in patients with advanced solid tumors and lymphomas.
EXPLORATORY OBJECTIVES:
I. Evaluate the effect of the doublet and triplet combinations on markers of anti-tumor immunity in circulating immune cells and pre- and post-treatment tumor biopsies.
II. Evaluate the effect of the combinations on biomarkers of AKT inhibition, deoxyribonucleic acid (DNA) damage (gammaH2AX, pNbs1, Rad51), apoptosis, and epithelial-mesenchymal transition in pre- and post- treatment tumor biopsies.
III. Assess preliminary antitumor activity of the combinations.
OUTLINE: This is a dose-escalation study of copanlisib and nivolumab, followed by a dose-expansion study.
COHORT I (DOUBLET TREATMENT PLAN): Patients receive copanlisib intravenously (IV) over 1 hour on days 1 and 15 or days 1, 8, and 15 of each cycle and nivolumab IV over 30 minutes on day 1 or days 1 and 15 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo computed tomography (CT) scan and/or magnetic resonance imaging (MRI) throughout the trial. Patients undergo blood sample collection on study and during follow-up, as well as tumor biopsy on study. Patients also undergo an echocardiography (ECHO) during screening and as clinically indicated on study.
COHORT II (TRIPLET SAFETY RUN-IN PHASE TREATMENT PLAN): Patients receive copanlisib IV over 1 hour on days 1, 8, and 15 of each cycle, nivolumab IV over 30 minutes on day 1 of each cycle, and ipilimumab IV over 90 minutes on day 1 for cycles 1-4. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT scan and/or MRI throughout the trial. Patients undergo an ECHO during screening and as clinically indicated on study.
COHORT III (TRIPLET TREATMENT PLAN): Patients receive copanlisib IV over 1 hour on days 1, 8, and 15 of each cycle, nivolumab IV over 30 minutes on day 15 of cycle 1 and then day 1 of each subsequent cycles, and ipilimumab IV over 90 minutes on day 1 for cycles 2-5. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT scan and/or MRI throughout the trial. Patients undergo blood sample collection on study and during follow-up, as well as tumor biopsy on study. Patients also undergo an ECHO during screening and as clinically indicated on study.
After completion of study treatment, patients are followed up monthly for 4 months.
Study Oversight
Has Oversight DMC:
False
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?: