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.

- Have histologically metastatic or unresectable microsatellite stable (MSS) solid tumor
cancer or microsatellite stable MSS colon cancer.

- 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.

- 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 P13K inhibitor

- Chemotherapy, radiotherapy, 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 progressive disease or 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.

- CMV PCR (cytomegalovirus polymerase chain reaction) positive.

- Known history or concurrent interstitial lung disease.

- HbA1c >8.5% at screening.

- 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.

- 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.