Unresectable or Metastatic Microsatellite Stable (MSS) Solid TumorPhase 1/2NCT03711058
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
A Phase 1/2 study testing Copanlisib and Nivolumab in people with Unresectable or Metastatic Microsatellite Stable (MSS) Solid Tumor and Microsatellite Stable (MSS) Colon Cancer, run by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Unresectable or Metastatic Microsatellite Stable (MSS) Solid Tumor, Microsatellite Stable (MSS) Colon Cancer
- What is being tested?
- Copanlisib and Nivolumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 48 participants
- Where
- 1 siteUnited States
- Study dates
- 17 Jan 2019to 30 Jun 2025
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
Sidney Kimmel Comprehensive Cancer Center
Baltimore, Maryland, 21231
About this study
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
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
- Being tested
- Copanlisib, Nivolumab
- Keywords
- Immunotherapy, Nivolumab, Copanlisib, Unresectable, Metastatic, PD-1, P13K, Antibody, Solid Tumors, Colon Cancer, MSS, Mismatch-repair proficient, Microsatellite stable
- Medical subject headings
- Spinocerebellar Degenerations, Colonic Neoplasms, Neoplasm Metastasis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CopanlisibDrug
Also called Bay 80-6946
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
NivolumabDrug
Also called OPDIVO, Bay 80-6946
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
| Study group | Role | What they receive |
|---|---|---|
| Phase I - Copanlisib and Nivolumab (De-Escalation) | Experimental | Not described Receives: Drug: Copanlisib; Drug: Nivolumab |
| Phase II /Arm A-P13K mutation/Copanlisib and Nivolumab | Experimental | Not described Receives: Drug: Copanlisib; Drug: Nivolumab |
| Phase II/Arm B -P13K wild type /Copanlisib and Nivolumab | Experimental | Not described Receives: Drug: Copanlisib; Drug: Nivolumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
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)
Measured: 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.
Measured: 6-months
Secondary outcomes (5)
Disease Control Rate (DCR) Status at 6 Months.
Percentage of participants achieving stable disease (SD) or better (SD + PR + CR).
Per RECIST 1.1, complete response is defined as disappearance of all target lesions, partial response is defined as at least a 30% decrease in the sum of diameters of target lesions, stable disease occurs when there is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (at least 20% increase). Lesions are assessed by CT or MRI.
Measured: 6-months
Duration of Response (DOR)
Number of months from the first documentation of a partial or complete response by RECIST 1.1 to date of disease progression. Responses may be documented at any time on the study, including patients responding after the 6-month evaluation used for the primary outcome.
Measured: 3 years
Progression Free Survival (PFS)
Number of months from treatment to disease progression (PD)
Measured: 3 years
Overall Survival (OS)
Number of months from the date of first treatment until death or end of follow-up.
Measured: 3 years
Number of Participants Experiencing Study Drug-related Toxicities
Number of participants experiencing study drug-related adverse events Grade 3 or higher as defined by CTCAE v5.0.
Measured: 51 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Oct 2018
- Study start17 Jan 2019
- Primary completion14 Jun 2022
- Study completion30 Jun 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Unresectable or Metastatic Microsatellite Stable (MSS) Solid TumorStudies of the same condition, open and under way.
- More trials run by Sidney Kimmel Comprehensive Cancer Center at Johns HopkinsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 48 participants (actual)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Collaborators
- Bayer, Bristol-Myers Squibb
- Responsible party
- Sponsor
- Investigators
- Nilofer Azad, MD, Principal investigator, Johns Hopkins Medical Institution
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03711058
- Sponsor's protocol ID
- J1887
- Other IDs
- IRB00175864, CA209-8LC
- Status last verified
- Aug 2025
- First submitted
- 15 Oct 2018
- Last updated
- 16 Sep 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Christenson ES, Wala JA, Parkinson R, Collins NB, Jakubowski C, Lin JR, Qian K, Lu J, Wang H, Ho WJ, Chan S, Kulikowicz E, Klein R, Cetasaan Y, Johnson E, Berg M, Meyerhardt JA, Le DT, Schlechter BL, Browner I, Zheng L, Singh H, Donehower R, Jaffee EM, Sorger PK, Giannakis M, Azad N. Copanlisib in combination with nivolumab formicrosatellite stable colorectal cancer: a phase 1/2 trial. Nat Commun. 2026 Jul 23;17(1):7114. doi: 10.1038/s41467-026-72985-6.
PubMed 42493490Morschhauser 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.
PubMed 31619463
Study at a glance
From the registry record, last updated by the sponsor on 16 Sep 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03711058
- Acronym / sponsor ID
- J1887
- Conditions
- Unresectable or Metastatic Microsatellite Stable (MSS) Solid Tumor, Microsatellite Stable (MSS) Colon Cancer
- Keywords
- Immunotherapy, Nivolumab, Copanlisib, Unresectable, Metastatic, PD-1, P13K, Antibody
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 48 participants (actual)
- Lead sponsor
- Sidney Kimmel Comprehensive Cancer Center at Johns HopkinsUniversity, hospital or other
- Collaborators
- Bayer, Bristol-Myers Squibb
- Study start
- 17 Jan 2019 (actual)
- Primary completion
- 14 Jun 2022 (actual)
- Study completion
- 30 Jun 2025 (actual)
- First posted
- 18 Oct 2018 (actual)
- Results
- Posted 15 Jun 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| 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 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- 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.
Key exclusion criteria (30 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CopanlisibAlso: Bay 80-6946Copanlisib 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 | Drug | 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 |
| NivolumabAlso: OPDIVO, Bay 80-6946Nivolumab 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 | Drug | 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 |
Primary outcome
Number of Participants Experiencing a Dose Limiting Toxicity
Time frame: 28 days
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)
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). 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.
5 secondary outcomes
Disease Control Rate (DCR) Status at 6 Months.
Time frame: 6-months
Duration of Response (DOR)
Time frame: 3 years
Progression Free Survival (PFS)
Time frame: 3 years
Overall Survival (OS)
Time frame: 3 years
Number of Participants Experiencing Study Drug-related Toxicities
Time frame: 51 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Sep 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 42493490Christenson ES, Wala JA, Parkinson R, Collins NB, Jakubowski C, Lin JR, Qian K, Lu J, Wang H, Ho WJ, Chan S, Kulikowicz E, Klein R, Cetasaan Y, Johnson E, Berg M, Meyerhardt JA, Le DT, Schlechter BL, Browner I, Zheng L, Singh H, Donehower R, Jaffee EM, Sorger PK, Giannakis M, Azad N. Copanlisib in combination with nivolumab formicrosatellite stable colorectal cancer: a phase 1/2 trial. Nat Commun. 2026 Jul 23;17(1):7114. doi: 10.1038/s41467-026-72985-6.
- Derived from this study: PubMed 31619463Morschhauser 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.
- Individual participant dataSharing planned: Undecided
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Nilofer Azad, MD principal investigator
Johns Hopkins Medical Institution
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Copanlisib and Nivolumab in people with Unresectable or Metastatic Microsatellite Stable (MSS) Solid Tumor and Microsatellite Stable (MSS) Colon Cancer, run by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 30 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 16 Sep 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 15 Jun 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants Experiencing a Dose Limiting Toxicity (time frame: 28 days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03711058, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Sep 2025.