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

NCT ID: NCT03711058

Last Updated: 2025-09-16

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 48 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-01-17
• Study Completion Date: 2025-06-30

Brief 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.

Conditions

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

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Phase I - Copanlisib and Nivolumab (De-Escalation)

Group Type: EXPERIMENTAL

Copanlisib

Intervention Type: DRUG

Copanlisib will be administered as a 60 minute IV infusion (-5min/+10min) at a dose of 45 mg - 60 mg IV. Copanlisib will be administered once a week (days 1, 8, and 15 or Day 1 and Day 15 of each 28 day cycle).

Drug: 45 or 60 mg IV

Nivolumab

Intervention Type: DRUG

Nivolumab 480 mg will be administered as a 30 minute IV infusion (-5min/+10min) on Day 1 of each 28 day cycle.

Drug: 480 mg IV

Phase II /Arm A-P13K mutation/Copanlisib and Nivolumab

Group Type: EXPERIMENTAL

Copanlisib

Intervention Type: DRUG

Copanlisib will be administered as a 60 minute IV infusion (-5min/+10min) at a dose of 45 mg - 60 mg IV. Copanlisib will be administered once a week (days 1, 8, and 15 or Day 1 and Day 15 of each 28 day cycle).

Drug: 45 or 60 mg IV

Nivolumab

Intervention Type: DRUG

Nivolumab 480 mg will be administered as a 30 minute IV infusion (-5min/+10min) on Day 1 of each 28 day cycle.

Drug: 480 mg IV

Phase II/Arm B -P13K wild type /Copanlisib and Nivolumab

Group Type: EXPERIMENTAL

Copanlisib

Intervention Type: DRUG

Copanlisib will be administered as a 60 minute IV infusion (-5min/+10min) at a dose of 45 mg - 60 mg IV. Copanlisib will be administered once a week (days 1, 8, and 15 or Day 1 and Day 15 of each 28 day cycle).

Drug: 45 or 60 mg IV

Nivolumab

Intervention Type: DRUG

Nivolumab 480 mg will be administered as a 30 minute IV infusion (-5min/+10min) on Day 1 of each 28 day cycle.

Drug: 480 mg IV

Interventions

Copanlisib

Copanlisib will be administered as a 60 minute IV infusion (-5min/+10min) at a dose of 45 mg - 60 mg IV. Copanlisib will be administered once a week (days 1, 8, and 15 or Day 1 and Day 15 of each 28 day cycle).

Drug: 45 or 60 mg IV

Intervention Type: DRUG

Nivolumab

Nivolumab 480 mg will be administered as a 30 minute IV infusion (-5min/+10min) on Day 1 of each 28 day cycle.

Drug: 480 mg IV

Intervention Type: DRUG

Other Intervention Names

Bay 80-6946; OPDIVO, Bay 80-6946

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Bayer

INDUSTRY

Sponsor Role: collaborator

Bristol-Myers Squibb

INDUSTRY

Sponsor Role: collaborator

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Nilofer Azad, MD

Role: PRINCIPAL_INVESTIGATOR

Johns Hopkins Medical Institution

Locations

Sidney Kimmel Comprehensive Cancer Center

Baltimore, Maryland, United States

Countries

United States

References

Morschhauser F, Machiels JP, Salles G, Rottey S, Rule SAJ, Cunningham D, Peyrade F, Fruchart C, Arkenau HT, Genvresse I, Liu L, Kochert K, Shen K, Kneip C, Pena CE, Grevel J, Zhang J, Cisternas G, Reschke S, Granvil C, Awada A. On-Target Pharmacodynamic Activity of the PI3K Inhibitor Copanlisib in Paired Biopsies from Patients with Malignant Lymphoma and Advanced Solid Tumors. Mol Cancer Ther. 2020 Feb;19(2):468-478. doi: 10.1158/1535-7163.MCT-19-0466. Epub 2019 Oct 16.

Reference Type: DERIVED

PMID: 31619463 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

IRB00175864

Identifier Type: OTHER

Identifier Source: secondary_id

CA209-8LC

Identifier Type: OTHER

Identifier Source: secondary_id

J1887

Identifier Type: -

Identifier Source: org_study_id