A Phase I/II Biomarker Driven Combination Trial of Copanlisib and Immune Checkpoint Inhibitors in Patients With Advanced Solid Tumors

• Patients must have histologically confirmed malignancy that is metastatic or unresectable and for which standard curative measures do not exist or are no longer effective

• Patients must be \>= 4 weeks beyond treatment with any chemotherapy or other investigational therapy to include hormonal, biological, or targeted agents; or at least 5 half-lives from hormonal, biological, or targeted agents, whichever is shorter at the time of treatment initiation

• Age \>= 18 years. Because no dosing or adverse event data are currently available on the use of copanlisib in combination with nivolumab (and ipilimumab) in patients \< 18 years of age, children are excluded from this study, but will be eligible for future pediatric trials

• Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1

• Absolute neutrophil count (ANC) \>= 1,500 /mcL

• Platelets \>= 100,000 / mcL

• Hemoglobin \>= 9 g/dL

• Serum creatinine =\< 1.5 x upper limit of normal (ULN) OR measured or calculated creatinine clearance (glomerular filtration rate \[GFR\] can also be used in place of creatinine or creatine clearance \[CrCl\]) \>= 60 mL/min for subject with creatinine levels \> 1.5 x institutional ULN (creatinine clearance should be calculated per institutional standard)

• Serum total bilirubin =\< 1.5 x ULN OR direct bilirubin =\< ULN for subjects with total bilirubin levels \> 1.5 x ULN

• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =\< 2.5 x ULN OR =\< 5 x ULN for subjects with liver metastases

• International normalized ratio (INR) or prothrombin time (PT) =\< 1.5 x ULN unless subject is receiving anticoagulant therapy as long as PT or partial thromboplastin time (PTT) is within therapeutic range of intended use of anticoagulants

• Activated partial thromboplastin time (aPTT) =\< 1.5 x ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants

• Patients must have measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1

• Patients must have a glycosylated hemoglobin (HbA1c) =\< 8.5% at screening and a fasting glucose of =\< 160 mg/dL

• Women of child-bearing potential MUST have a negative serum or urine human chorionic gonadotropin (HCG) test within 24 hours of study enrollment unless prior tubal ligation (\>= 1 year before screening), total hysterectomy or menopause (defined as 12 consecutive months of amenorrhea). Patients should not become pregnant or breastfeed while on this study. Sexually active patients must agree to use dual contraception for the duration of study participation and for 7 months after the last dose of study treatment for women of childbearing potential and 5 months for men with partners that are women of childbearing potential

• Patients need to have biopsiable disease to enroll on Trial 1 (copanlisib + nivolumab)

• Patients in dose escalation and expansion of all arms must have actionable mutations in either PIK3CA hotspot (E542, E545, or H1047 are accepted) or PTEN (except for specific wild type cohorts). Local testing in Clinical Laboratory Improvement Amendments (CLIA)-certified laboratory will be accepted. Only mutations that have been recognized as actionable by the MD Anderson Precision Oncology Decision Support (PODS) team will be accepted

• Ability to understand and the willingness to sign a written informed consent document

• Patients who have previously received PD-1/PD-L1/PI3K inhibitors will be eligible for this study