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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ClinicalTrials.gov Identifier: NCT03711058 |
Recruitment Status :
Recruiting
First Posted : October 18, 2018
Last Update Posted : August 9, 2022
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Condition or disease | Intervention/treatment | Phase |
---|---|---|
Unresectable or Metastatic Microsatellite Stable (MSS) Solid Tumor Along With Microsatellite Stable (MSS) Colon Cancer Colon Cancer | Drug: Copanlisib Drug: Nivolumab | Phase 1 Phase 2 |
Study Type : | Interventional (Clinical Trial) |
Estimated Enrollment : | 54 participants |
Allocation: | Non-Randomized |
Intervention Model: | Sequential Assignment |
Masking: | None (Open Label) |
Primary Purpose: | Treatment |
Official Title: | 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 |
Actual Study Start Date : | January 17, 2019 |
Actual Primary Completion Date : | May 4, 2022 |
Estimated Study Completion Date : | January 2023 |

Arm | Intervention/treatment |
---|---|
Experimental: Phase I - Copanlisib and Nivolumab (De-Escalation) |
Drug: 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 Other Name: Bay 80-6946 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 Other Name: OPDIVO, Bay 80-6946 |
Experimental: Phase II - Copanlisib and Nivolumab |
Drug: 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 Other Name: Bay 80-6946 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 Other Name: OPDIVO, Bay 80-6946 |
- Determine maximum tolerated dose (MTD) of copanlisib with fixed dose nivolumab [ Time Frame: 2 years ]Number of patients having a dose limiting toxicities (DLT) at each level.
- 6-month objective response rate (ORR) of patients treated with copanlisib and nivolumab [ Time Frame: 6-months ]The proportion of subjects with partial response (PR) or complete response (CR) as defined by Response Evaluation Criteria in Solid Tumors (RECIST 1.1)
- Disease control rate (DCR) status at 6 months. [ Time Frame: 6-months ]Percentage of participants achieving stable disease (SD) or better (SD + partial response (PR) + (CR).
- Duration of response (DOR) status at 6 months. [ Time Frame: 6-months ]Number of months from the first documentation of a response to date of disease progression.
- Progression free survival (PFS) status at 6 months. [ Time Frame: 6-months ]Number of months from treatment to disease progression (PD)
- Overall survival (OS) status at 6 months. [ Time Frame: 6-months ]Number of months from the date of first treatment until death or end of follow-up.
- Number of participants experiencing study drug-related toxicities [ Time Frame: 2 years ]Number of participants experiencing study drug-related adverse events Grade 3 or higher as defined by CTCAE v5.0.

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Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
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.

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03711058
Contact: Trish Brothers, RN | 410-614-3644 | GIClinicalTrials@jhmi.edu | |
Contact: Joann Santmyer, RN | 410-614-3644 | GIClinicalTrials@jhmi.edu |
United States, Maryland | |
Sidney Kimmel Comprehensive Cancer Center | Recruiting |
Baltimore, Maryland, United States, 21231 | |
Contact: Trish Brothers, RN 410-614-3644 GIClinicalTrials@jhmi.edu | |
Contact: Joann Santmyer, RN 410-614-3644 GIClinicalTrials@jhmi.edu |
Principal Investigator: | Nilofer Azad, MD | Johns Hopkins Medical Institution |
Responsible Party: | Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins |
ClinicalTrials.gov Identifier: | NCT03711058 |
Other Study ID Numbers: |
J1887 IRB00175864 ( Other Identifier: JHM IRB ) CA209-8LC ( Other Identifier: Bristol-Myers Squibb ) |
First Posted: | October 18, 2018 Key Record Dates |
Last Update Posted: | August 9, 2022 |
Last Verified: | August 2022 |
Individual Participant Data (IPD) Sharing Statement: | |
Plan to Share IPD: | Undecided |
Studies a U.S. FDA-regulated Drug Product: | Yes |
Studies a U.S. FDA-regulated Device Product: | No |
Immunotherapy Nivolumab Copanlisib Unresectable Metastatic PD-1 P13K |
Antibody Solid Tumors Colon Cancer MSS Mismatch-repair proficient Microsatellite stable |
Colonic Neoplasms Neoplasms Colorectal Neoplasms Intestinal Neoplasms Gastrointestinal Neoplasms Digestive System Neoplasms Neoplasms by Site Digestive System Diseases |
Gastrointestinal Diseases Colonic Diseases Intestinal Diseases Nivolumab Antineoplastic Agents, Immunological Antineoplastic Agents Immune Checkpoint Inhibitors Molecular Mechanisms of Pharmacological Action |