Study of PI3Kinase Inhibition (Copanlisib) and Anti-PD-1 Antibody Nivolumab in Relapsed/Refractory Solid Tumors With Expansions in Mismatch-repair Proficient (MSS) Colorectal Cancer

Inclusion Criteria:

* Age ≥18 years.
* Ability to understand and willingness to sign a written informed consent document.
* Phase I: Must have received all curative treatment options and at least 2 lines of systemic therapy.
* Phase II: Must have received at least 2 lines of systemic therapy including a fluoropyrimidine, oxaliplatin, and irinotecan-containing regimen. KRAS/NRAS/BRAF wildtype patients must have received or refused anti-EGR.
* Must have received all curative treatment options and at least 2 lines of systemic and standard therapy.
* Must have measurable disease based on RECIST 1.1
* Must have biopsiable disease.
* Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
* Life expectancy of greater than 3 months.
* Patients must have adequate organ and marrow function defined by study-specified laboratory tests within 21 days of initial study drug.
* Men must use acceptable form of birth control while on study.
* Woman of childbearing potential must have a negative pregnancy test and follow contraceptive guidelines as defined per protocol.

Exclusion Criteria:

* Prior treatment with immunotherapy agents (including, anti-PD-1, anti-PD-L1, anti- PD-L2, anti-CTLA4, etc.).
* Prior therapy with a PI3K inhibitor
* Chemotherapy, target small molecule therapy, investigational therapy, or surgery within 4 weeks prior to first dose of treatment.
* Has received prior radiotherapy within 2 weeks prior to the start of treatment.
* Patient who is receiving or have received any other investigational agents within 4 weeks prior to the first dose of treatment.
* Has received a live vaccine 30 days prior to the first dose of study drug.
* Has known additional malignancy that is progressing or requires active treatment..
* Has known central nervous system (CNS) metastases and/or carcinomatous meningitis.
* Has symptomatic ascites or has required a paracentesis in the last 12 weeks.
* Hypersensitivity reaction to study drug.
* Patients diagnosed of immunodeficiency or are on any immunosuppressive agents within 7 days prior to first dose of study drug.
* Has active autoimmune disease that has required systemic treatment in the past 12 months, or a documented history of clinically severe autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive agents.
* Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis.
* Has an active infection requiring systemic therapy.
* Infection with HIV or hepatitis B or C.
* Cytomegalovirus polymerase chain reaction (CMV PCR) positive.
* Known history or concurrent interstitial lung disease.
* Type I diabetes or Type II diabetes requiring treatment with a sulfonylurea, meglitinide, or insulin at screening.
* Uncontrolled cardiovascular disease.
* Patient with uncontrolled intercurrent illness including, but not limited to, uncontrolled infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
* Use of anti-arrhythmic therapy (beta blockers or digoxin are permitted).
* Use of CYP3A4 inhibitors and inducers within 2 weeks of starting study drug and throughout treatment.
* Any arterial or venous thrombotic or embolic events within 3 months of start of study drug.
* Non-healing wound, ulcer, or fracture.
* Patients with evidence or history of bleeding condition.
* Had a blood or platelet transfusion within 7 days of Cycle 1 Day 1 treatment.
* Seizure disorder requiring anti-seizure medication.
* Conditions, including alcohol or drug dependence, intercurrent illness, or lack of sufficient peripheral venous access, that would affect the patient's ability to comply with study visits and procedures.
* Are pregnant or breastfeeding.
* Unwilling or unable to follow the study schedule for any reason.