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

Conditions: Unresectable or Metastatic Microsatellite Stable (MSS) Solid Tumor Along With Microsatellite Stable (MSS) Colon Cancer; Colon 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 criteria:
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.

Keywords: immunotherapy nivolumab copanlisib unresectable metastatic pd-1 p13k antibody solid tumors colon cancer mss mismatch-repair proficient microsatellite stable