This phase I/II trial studies the side effects and best dose of copanlisib when given together with nivolumab and ipilimumab and to see how well they work in treating patients with solid cancers that may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced) and have changes in PIK3CA and PTEN genes. Copanlisib may stop the growth of tumor cells by blocking some of the enzymes needed for 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. The addition of copanlisib to usual immunotherapy may work better in treating patients with solid cancers compared to usual immunotherapy alone.
PRIMARY OBJECTIVE:
I. To evaluate safety and confirm the combination recommended phase 2 dose (RP2D) of the combination of copanlisib, nivolumab (and ipilimumab) in patients with molecularly-selected advanced solid tumors.
SECONDARY OBJECTIVES:
I. To observe and record antitumor activity. II. To assess clinical benefit of copanlisib in combination with nivolumab (and ipilimumab) in patients with molecularly-selected advanced solid tumors, as measured by objective response (OR) = complete response (CR) + partial response (PR).
III. To assess overall duration of response (DoR), progression free survival (PFS), and overall survival (OS).
IV. To assess immune-modulatory changes associated with copanlisib-induced PI3K inhibition and combination of copanlisib and nivolumab (and ipilimumab).
V. To correlate molecular alterations in the PI3K-AKT pathway and treatment induced immune-modulatory changes with objective response (OR).
EXPLORATORY OBJECTIVES:
I. To perform molecular profiling assays on malignant and normal tissues, including, but not limited to, whole exome sequencing (WES), ribonucleic acid (RNA) sequencing, reverse phase protein array (RPPA), circulating tumor deoxyribonucleic acid (DNA) analysis, and immune profiling in order to:
Ia. Identify potential predictive and prognostic biomarkers beyond any genomic alteration by which treatment may be assigned; Ib. Identify resistance mechanisms using genomic DNA- and RNA-based assessment platforms.
II. To contribute genetic analysis data from de-identified biospecimens to Genomic Data Commons (GDC), a well annotated cancer molecular and clinical data repository, for current and future research.
III. To bank formalin-fixed, paraffin-embedded (FFPE) tissue, blood (for cell-free DNA analysis), and nucleic acids obtained from patients at the Early-Phase and Experimental Clinical Trials (EET) Biobank at Nationwide Children's Hospital.
OUTLINE: This is a phase I, dose-escalation study of copanlisib followed by a phase II study. Patients are assigned to 1 of 2 trials.
TRIAL I: Patients receive copanlisib hydrochloride intravenously (IV) over 1 hour on days 1, 8, and 15 of cycle 1. Beginning in cycle 2, patients also receive nivolumab IV over 60 minutes on day 1. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo an x-ray and/or computed tomography (CT) scan, as well as a tumor biopsy during screening and on study. Patients also undergo blood sample collection on study.
TRIAL II: Patients receive copanlisib hydrochloride IV over 1 hour on days 1, 8, and 15 of cycle 1. Beginning in cycle 2, patients also receive nivolumab IV over 60 minutes on day 1 and ipilimumab IV over 90 minutes every 8 weeks for 4 doses. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo an x-ray and/or CT scan, as well as a tumor biopsy during screening and on study. Patients also undergo blood sample collection on study.
After completion of study treatment, patients are followed up at 30 days and then every 3-6 months for up to 2 years.
| Condition | Advanced Malignant Solid Neoplasm, Metastatic Malignant Solid Neoplasm, Unresectable Malignant Solid Neoplasm |
|---|---|
| Treatment | biopsy, computed tomography, Ipilimumab, Nivolumab, biospecimen collection, X-Ray Imaging, Copanlisib Hydrochloride |
| Clinical Study Identifier | NCT04317105 |
| Sponsor | National Cancer Institute (NCI) |
| Last Modified on | 29 July 2023 |
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