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

NCT03711058 | Completed Phase 1 Results DMC FDA Drug

• 3 other identifiers: J1887IRB00175864CA209-8LC
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 1

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

Keywords

Immunotherapy; Nivolumab; Copanlisib; Unresectable; Metastatic; PD-1; P13K; Antibody; Solid Tumors; Colon Cancer; MSS; Mismatch-repair proficient; Microsatellite stable

Outcome Measures

Primary Outcomes (2)

• Number of Participants Experiencing a Dose Limiting Toxicity

  Number of participants experiencing a Dose Limiting Toxicity (DLT) in each dose level. DLT is defined as any of the following study drug-related toxicities occurring during the first cycle of study drug on study: * Grade 4 anemia * Grade ≥ 3 neutropenia lasting ≥ 14 days * Grade ≥ 3 febrile neutropenia * Grade 4 thrombocytopenia, or Grade 3 thrombocytopenia with clinically significant bleeding * Treatment-related ≥ grade 4 AEs, except transient hyperglycemia * Grade ≥ 3 Pneumonitis or recurrent Grade 2 pneumonitis * Grade ≥ 3 Nephritis * Grade ≥ 3 elevated AST or ALT * Grade ≥ 2 eye pain or reduction of visual acuity that does not respond to topical therapy, improve to ≤ grade 1 within 2 weeks of topical therapy, or requires systemic therapy * Any other Grade ≥ 3 toxicities (with certain exceptions for transient AEs or asymptomatic labs)

  28 days

• 6-month Objective Response Rate (ORR) of Patients Treated With Copanlisib and Nivolumab

  The proportion of subjects with partial response (PR) or complete response (CR) as defined by Response Evaluation Criteria in Solid Tumors (RECIST 1.1). Per RECIST 1.1, complete response is defined as disappearance of all target lesions, and partial response is defined as at least a 30% decrease in the sum of diameters of target lesions. Lesions are assessed by CT or MRI.

  6-months

Secondary Outcomes (5)

• Disease Control Rate (DCR) Status at 6 Months.

  6-months

• Duration of Response (DOR)

  3 years

• Progression Free Survival (PFS)

  3 years

• Overall Survival (OS)

  3 years

• Number of Participants Experiencing Study Drug-related Toxicities

  51 months

Study Arms (3)

Phase I - Copanlisib and Nivolumab (De-Escalation)

EXPERIMENTAL

Drug: Copanlisib; Drug: Nivolumab

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

EXPERIMENTAL

Drug: Copanlisib; Drug: Nivolumab

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

EXPERIMENTAL

Drug: Copanlisib; Drug: Nivolumab

Interventions

Copanlisib 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

Also known as: Bay 80-6946

Phase I - Copanlisib and Nivolumab (De-Escalation); Phase II /Arm A-P13K mutation/Copanlisib and Nivolumab; Phase II/Arm B -P13K wild type /Copanlisib and Nivolumab

Nivolumab 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

Also known as: OPDIVO, Bay 80-6946

Phase I - Copanlisib and Nivolumab (De-Escalation); Phase II /Arm A-P13K mutation/Copanlisib and Nivolumab; Phase II/Arm B -P13K wild type /Copanlisib and Nivolumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins: lead
• Bayer: collaborator
• Bristol-Myers Squibb: collaborator

Study Sites (1)

Sidney Kimmel Comprehensive Cancer Center

Baltimore, Maryland, 21231, United States

Location

Related Publications (1)

• 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.

  PMID: 31619463 DERIVED

MeSH Terms

Conditions

Spinocerebellar Degenerations; Colonic Neoplasms; Neoplasm Metastasis

Interventions

copanlisib; Nivolumab

Condition Hierarchy (Ancestors)

Cerebellar Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Spinal Cord Diseases; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Nilofer Azad, MD
• Organization: Sidney Kimmel Cancer Center at Johns Hopkins

nazad2@jhmi.edu

610-614-9169

Study Officials

• Nilofer Azad, MD

  Johns Hopkins Medical Institution

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 15, 2018
• First Posted: October 18, 2018
• Study Start: January 17, 2019
• Primary Completion: June 14, 2022
• Study Completion: June 30, 2025
• Last Updated: September 16, 2025
• Results First Posted: June 15, 2023

Record last verified: 2025-08

Locations

US (1)