Patient case: 68-year-old male with colon cancer; genetic feature: MLH1 methylation suppression (microsatellite instability)

Clinical trial: 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

Summary: A phase I/II 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.


Eligibility: 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.

Relevance to patient case: not relevant