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

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Johns Hopkins Medicine

Status and phase

Active, not recruiting
Phase 2
Phase 1


Colon Cancer
Unresectable or Metastatic Microsatellite Stable (MSS) Solid Tumor Along With Microsatellite Stable (MSS) Colon Cancer


Drug: Copanlisib
Drug: Nivolumab

Study type


Funder types



CA209-8LC (Other Identifier)
IRB00175864 (Other Identifier)

Details and patient eligibility


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.


48 patients




18+ years old


No Healthy Volunteers

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.

Trial design

Primary purpose




Interventional model

Sequential Assignment


None (Open label)

48 participants in 3 patient groups

Phase I - Copanlisib and Nivolumab (De-Escalation)
Experimental group
Drug: Nivolumab
Drug: Copanlisib
Phase II /Arm A-P13K mutation/Copanlisib and Nivolumab
Experimental group
Drug: Nivolumab
Drug: Copanlisib
Phase II/Arm B -P13K wild type /Copanlisib and Nivolumab
Experimental group
Drug: Nivolumab
Drug: Copanlisib

Trial documents

Trial contacts and locations



Data sourced from

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