- 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
- Phase II: Must have received at least 2 lines of systemic therapy including a
fluropyrimidine, 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
- 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.
- 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
- 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.
- 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
- Any arterial or venous thrombotic or embolic events within 3 months of start of study
- 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.