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

• Status: Recruiting
• Trial end date: 2022-01-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• Collaborators: Bayer; Bristol-Myers Squibb
• Treatments: Antibodies; Antibodies, Monoclonal; Immunoglobulins; Nivolumab

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 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 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 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.

• 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 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.