Advanced Malignant Solid NeoplasmPhase 1/2NCT04317105
Testing the Addition of an Anti-cancer Drug, Copanlisib, to the Usual Immunotherapy (Nivolumab With or Without Ipilimumab) in Patients With Advanced Solid Cancers That Have Changes in the Following Genes: PIK3CA and PTEN
A Phase 1/2 study testing Biopsy Procedure, Biospecimen Collection and Computed Tomography in people with Advanced Malignant Solid Neoplasm and Metastatic Malignant Solid Neoplasm, run by National Cancer Institute (NCI) at 6 sites in 2 countries.
Trial summary
This phase I/II trial studies the side effects and best dose of copanlisib when given together with nivolumab and ipilimumab and to see how well they work in treating patients with solid cancers that may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced) and… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Advanced Malignant Solid Neoplasm, Metastatic Malignant Solid Neoplasm, Unresectable Malignant Solid Neoplasm
- What is being tested?
- Biopsy Procedure, Biospecimen Collection and Computed Tomography
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 54 participants
- Where
- 6 sitesin 2 countries
- Study dates
- 17 Jul 2020to 6 May 2027
- 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
- Patients must have histologically confirmed malignancy that is metastatic or unresectable and for which standard curative measures do not exist or are no longer effective
- Patients must be >= 4 weeks beyond treatment with any chemotherapy or other investigational therapy to include hormonal, biological, or targeted agents; or at least 5 half-lives from hormonal, biological, or targeted agents, whichever is shorter at the time of treatment initiation
- Age >= 18 years. Because no dosing or adverse event data are currently available on the use of copanlisib in combination with nivolumab (and ipilimumab) in patients < 18 years of age, children are excluded from this study, but will be eligible for future pediatric trials
- Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1
- Absolute neutrophil count (ANC) >= 1,500 /mcL
- Platelets >= 100,000 / mcL
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- Hemoglobin >= 9 g/dL
- Serum creatinine =< 1.5 x upper limit of normal (ULN) OR measured or calculated creatinine clearance (glomerular filtration rate [GFR] can also be used in place of creatinine or creatine clearance [CrCl]) >= 60 mL/min for subject with creatinine levels > 1.5 x institutional ULN (creatinine clearance should be calculated per institutional standard)
- Serum total bilirubin =< 1.5 x ULN OR direct bilirubin =< ULN for subjects with total bilirubin levels > 1.5 x ULN
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 x ULN OR =< 5 x ULN for subjects with liver metastases
- International normalized ratio (INR) or prothrombin time (PT) =< 1.5 x ULN unless subject is receiving anticoagulant therapy as long as PT or partial thromboplastin time (PTT) is within therapeutic range of intended use of anticoagulants
- Activated partial thromboplastin time (aPTT) =< 1.5 x ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants
- Patients must have measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1
- Patients must have a glycosylated hemoglobin (HbA1c) =< 8.5% at screening and a fasting glucose of =< 160 mg/dL
- Women of child-bearing potential MUST have a negative serum or urine human chorionic gonadotropin (HCG) test within 24 hours of study enrollment unless prior tubal ligation (>= 1 year before screening), total hysterectomy or menopause (defined as 12 consecutive months of amenorrhea). Patients should not become pregnant or breastfeed while on this study. Sexually active patients must agree to use dual contraception for the duration of study participation and for 7 months after the last dose of study treatment for women of childbearing potential and 5 months for men with partners that are women of childbearing potential
- Patients need to have biopsiable disease to enroll on Trial 1 (copanlisib + nivolumab)
- Patients in dose escalation and expansion of all arms must have actionable mutations in either PIK3CA hotspot (E542, E545, or H1047 are accepted) or PTEN (except for specific wild type cohorts). Local testing in Clinical Laboratory Improvement Amendments (CLIA)-certified laboratory will be accepted. Only mutations that have been recognized as actionable by the MD Anderson Precision Oncology Decision Support (PODS) team will be accepted
- Ability to understand and the willingness to sign a written informed consent document
- Patients who have previously received PD-1/PD-L1/PI3K inhibitors will be eligible for this study
Who cannot join
- Patients who are receiving any other investigational agents
- Pregnant or breastfeeding women will be excluded from participation in this trial, as there is no significant clinical information regarding the effects of copanlisib, nivolumab, and ipilimumab on a fetus or newborn infant
- Known active hepatitis B or hepatitis C infection. All patients must be screened for hepatitis B virus (HBV) and hepatitis C virus (HCV) up to 28 days prior to study drug start using the routine hepatitis virus lab panel. Patients positive for hepatitis B virus surface antigen (HBsAg) and/or hepatitis B virus core antibody (HBcAb) will be eligible if they are negative for HBV DNA, these patients should receive prophylactic antiviral therapy. Patients positive for anti-HCV antibody will be eligible if they are negative for HCV RNA
- Human immunodeficiency virus (HIV)-infected (HIV1/2 antibody-positive) patients may participate IF they meet all the following eligibility requirements:
- They must be on an anti-retroviral regimen with evidence of at least two undetectable viral loads within the past 6 months on this same regimen; the most recent undetectable viral load must be within the past 12 weeks
- They must have a CD4 count >= 250 cells/mcL over the past 6 months on this same anti-retroviral regimen and must not have had a CD4 count < 200 cells/ mcL over the past 2 years, unless it was deemed related to the cancer and/or chemotherapy-induced bone marrow suppression
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- For patients who have received chemotherapy in the past 6 months, a CD4 count < 250 cells/mcL during chemotherapy is permitted as long as viral loads were undetectable during this same chemotherapy
- They must have an undetectable viral load and a CD4 count >= 250 cells/mcL within 7 days of enrollment
- They must not be currently receiving prophylactic therapy for an opportunistic infection and must not have had an opportunistic infection within the past 6 months
- Active infection requiring intravenous (IV) antibiotics or other uncontrolled intercurrent illness requiring hospitalization
- Active autoimmune disease or history of autoimmune disease that might recur, which may affect vital organ function or require immune suppressive treatment including systemic corticosteroids. Exceptions include vitiligo, type I diabetes mellitus, endocrine deficiencies including thyroiditis managed with replacement hormones including physiologic corticosteroids, Sjogren's syndrome
- Inability to comply with the study and follow-up procedures
- History of cerebrovascular accident (CVA), myocardial infarction, or unstable angina within the previous 6 months before starting therapy
- Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin that has undergone curative therapy, or in situ cervical cancer
- Has a known psychiatric or substance abuse disorder that would interfere with cooperation with the requirements of the trial
- Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least 4 weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment. This exception does not include carcinomatous meningitis which is excluded regardless of clinical stability
- History of any clinically significant drug allergy or hypersensitivity to compounds of similar chemical or biologic composition to copanlisib, PI3K inhibitors, nivolumab, and ipilimumab (such as anaphylaxis or hepatotoxicity)
- Has known history of psoriasis even if not active at the time given may pose additional risks of immune activation with the combination regimen
- Patients with live vaccines and live, attenuated vaccines (prohibited for 30 days prior to study agents, during the study, and for 100 days after the last dose of study drug). Patients with inactivated vaccines are permitted
- Copanlisib is primarily metabolized by CYP3A4. Therefore, the concomitant use of strong inhibitors of CYP3A4 (e.g. ketoconazole, itraconazole, clarithromycin, ritonavir, indinavir, nelfinavir, and saquinavir) and strong inducers of CYP3A4 (e.g. rifampin, phenytoin, carbamazepine, phenobarbital, St. John's wort) is not permitted from 14 days prior to enrollment until the end of the study. Other medications that are prohibited while on copanlisib treatment include:
- Herbal medications/preparations (except vitamins)
- Anti-arrhythmic therapy other than beta blockers or digoxin
- Patients will be excluded if they have a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids and adrenal replacement doses > 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease. Patients are permitted to use topical, ocular, intra-articular, intranasal, and inhalational corticosteroids (with minimal systemic absorption). A brief course of corticosteroids for prophylaxis (e.g., contrast dye allergy) or for treatment of non-autoimmune conditions (e.g., delayed-type hypersensitivity reaction caused by contact allergen) is permitted. The use of corticosteroids as antiemetics prior to copanlisib administration will not be allowed
Trial locations and contacts
6 sites in 2 countries.
6 sites in 2 countries
United States5 sites
University of Texas at Austin
Austin, Texas, 78712
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215
University of Texas Medical Branch
Galveston, Texas, 77555-0565
UT MD Anderson Cancer Center
Houston, Texas, 77030
VCU Massey Comprehensive Cancer Center
Richmond, Virginia, 23298
Canada1 site
University Health Network-Princess Margaret Hospital
Toronto, Ontario, M5G 2M9
About this study
Official title: A Phase I/II Biomarker Driven Combination Trial of Copanlisib and Immune Checkpoint Inhibitors in Patients With Advanced Solid Tumors
This phase I/II trial studies the side effects and best dose of copanlisib when given together with nivolumab and ipilimumab and to see how well they work in treating patients with solid cancers that may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced) and have changes in PIK3CA and PTEN genes. Copanlisib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Immunotherapy with monoclonal antibodies, such as nivolumab and ipilimumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. The addition of copanlisib to usual immunotherapy may work better in treating patients with solid cancers compared to usual immunotherapy alone.
Read the detailed description
PRIMARY OBJECTIVE:
- To evaluate safety and confirm the combination recommended phase 2 dose (RP2D) of the combination of copanlisib, nivolumab (and ipilimumab) in patients with molecularly-selected advanced solid tumors.
SECONDARY OBJECTIVES:
- To observe and record antitumor activity. II. To assess clinical benefit of copanlisib in combination with nivolumab (and ipilimumab) in patients with molecularly-selected advanced solid tumors, as measured by objective response (OR) = complete response (CR) + partial response (PR).
III. To assess overall duration of response (DoR), progression free survival (PFS), and overall survival (OS).
IV. To assess immune-modulatory changes associated with copanlisib-induced PI3K inhibition and combination of copanlisib and nivolumab (and ipilimumab).
- To correlate molecular alterations in the PI3K-AKT pathway and treatment induced immune-modulatory changes with objective response (OR).
EXPLORATORY OBJECTIVES:
- To perform molecular profiling assays on malignant and normal tissues, including, but not limited to, whole exome sequencing (WES), ribonucleic acid (RNA) sequencing, reverse phase protein array (RPPA), circulating tumor deoxyribonucleic acid (DNA) analysis, and immune profiling in order to:
Ia. Identify potential predictive and prognostic biomarkers beyond any genomic alteration by which treatment may be assigned; Ib. Identify resistance mechanisms using genomic DNA- and RNA-based assessment platforms.
II. To contribute genetic analysis data from de-identified biospecimens to Genomic Data Commons (GDC), a well annotated cancer molecular and clinical data repository, for current and future research.
III. To bank formalin-fixed, paraffin-embedded (FFPE) tissue, blood (for cell-free DNA analysis), and nucleic acids obtained from patients at the Early-Phase and Experimental Clinical Trials (EET) Biobank at Nationwide Children's Hospital.
OUTLINE: This is a phase I, dose-escalation study of copanlisib followed by a phase II study. Patients are assigned to 1 of 2 trials.
TRIAL I: Patients receive copanlisib hydrochloride intravenously (IV) over 1 hour on days 1, 8, and 15 of cycle 1. Beginning in cycle 2, patients also receive nivolumab IV over 60 minutes on day 1. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo an x-ray and/or computed tomography (CT) scan during screening and every 8 weeks, as well as a tumor biopsy at baseline, cycle 1 day 15, cycle 2 day 15, and every 3 weeks thereafter, and at disease progression. Patients also undergo blood sample collection at baseline, cycle 1 days 8 and 15, cycle 2 day 15, cycle 4 day 1 and disease progression. Patients undergo echocardiography (ECHO) during screening and as clinically indicated on study.
TRIAL II: Patients receive copanlisib hydrochloride IV over 1 hour on days 1, 8, and 15 of cycle 1. Beginning in cycle 2, patients also receive nivolumab IV over 60 minutes on day 1 and ipilimumab IV over 90 minutes every 8 weeks for 4 doses. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo an x-ray and/or CT scan during screening and every 8 weeks, as well as a tumor biopsy at baseline, cycle 1 day 15, cycle 2 day 15, and every 3 weeks thereafter, and at disease progression. Patients also undergo blood sample collection at baseline, cycle 1 days 8 and 15, cycle 2 day 15, cycle 4 day 1 and disease progression. Patients undergo ECHO during screening and as clinically indicated on study.
After completion of study treatment, patients are followed up at 30 days and then every 3-6 months for up to 2 years.
- Conditions
- Advanced Malignant Solid Neoplasm, Metastatic Malignant Solid Neoplasm, Unresectable Malignant Solid Neoplasm
- Being tested
- Biopsy Procedure, Biospecimen Collection, Computed Tomography, Copanlisib Hydrochloride, Echocardiography Test
- Medical subject headings
- Neoplasm Metastasis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Biopsy ProcedureProcedure or surgery
Also called Biopsy, BIOPSY_TYPE, Bx
Undergo a tumor biopsy
Biospecimen CollectionProcedure or surgery
Also called Biological Sample Collection, Biospecimen Collected, Sample Collection, Specimen Collection
Undergo blood sample collection
Computed TomographyProcedure or surgery
Also called CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography
Undergo a CT scan
Copanlisib HydrochlorideDrug
Also called 5-Pyrimidinecarboxamide, 2-Amino-N-(2,3-dihydro-7-methoxy-8-(3-(4-morpholinyl)propoxy)imidazo(1,2-C)quinazolin-5-yl)-, Hydrochloride (1:2), Aliqopa, BAY 80-6946 Dihydrochloride, BAY-80-6946 Dihydrochloride
Given IV
Echocardiography TestProcedure or surgery
Also called EC, Echocardiography
Undergo ECHO
IpilimumabBiological
Also called Anti-Cytotoxic T-Lymphocyte-Associated Antigen-4 Monoclonal Antibody, BMS 734016, BMS-734016, BMS734016
Given IV
NivolumabBiological
Also called ABP 206, BCD-263, BMS 936558, BMS-936558
Given IV
X-Ray ImagingProcedure or surgery
Also called Conventional X-Ray, Diagnostic Radiology, Medical Imaging, X-Ray, Plain film radiographs
Undergo an x-ray
| Study group | Role | What they receive |
|---|---|---|
| Trial I (copanlisib, nivolumab) | Experimental | Patients receive copanlisib hydrochloride IV over 1 hour on days 1, 8, and 15 of cycle 1. Beginning in cycle 2, patients also receive nivolumab IV over 60 minutes on day 1. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo an x-ray and/or CT scan during screening and every 8 weeks, as well as a tumor biopsy at baseline, cycle 1 day 15, cycle 2 day 15, and every 3 weeks thereafter, and at disease progression. Patients also undergo blood sample collection at baseline, cycle 1 days 8 and 15, cycle 2 day 15, cycle 4 day 1 and disease progression. Patients undergo ECHO during screening and as clinically indicated on study. Receives: Procedure: Biopsy Procedure; Procedure: Biospecimen Collection; Procedure: Computed Tomography; Drug: Copanlisib Hydrochloride; Procedure: Echocardiography Test; Biological: Nivolumab; Procedure: X-Ray Imaging |
| Trial II (copanlisib, nivolumab, ipilimumab) | Experimental | Patients receive copanlisib hydrochloride IV over 1 hour on days 1, 8, and 15 of cycle 1. Beginning in cycle 2, patients also receive nivolumab IV over 60 minutes on day 1 and ipilimumab IV over 90 minutes every 8 weeks for 4 doses. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo an x-ray and/or CT scan during screening and every 8 weeks, as well as a tumor biopsy at baseline, cycle 1 day 15, cycle 2 day 15, and every 3 weeks thereafter, and at disease progression. Patients also undergo blood sample collection at baseline, cycle 1 days 8 and 15, cycle 2 day 15, cycle 4 day 1 and disease progression. Patients undergo ECHO during screening and as clinically indicated on study. Receives: Procedure: Biopsy Procedure; Procedure: Biospecimen Collection; Procedure: Computed Tomography; Drug: Copanlisib Hydrochloride; Procedure: Echocardiography Test; Biological: Ipilimumab; Biological: Nivolumab; Procedure: X-Ray Imaging |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Patients With Dose Limiting Toxicities as a Measure of Safety Profile to Determine the Recommended Phase 2 Dose (RP2D).
A DLT was evaluated according to the NCI CTCAE v5.0 and defined as Grade 4 neutropenia lasting greater than 7 days, febrile neutropenia, neutropenic infection, greater than or equal to grade 3 thrombocytopenia with bleeding, grade 4 thrombocytopenia, grade 4 anemia, non-hematologic greater than or equal to grade 4 toxicities, significant increase in QTc prolongation compared to baseline, grade 3 skin rash or diarrhea despite intervention, any any event that is greater than at baseline and is unacceptable according to the investigator and safety review committee.
Measured: The DLT monitoring time frame consisted of the first and second 28-day cycles.
Secondary outcomes (4)
Objective Response Rate (ORR)= Complete Response [CR] + Partial Response [PR])
Anti-tumor activity of the combination of copanlisib and nivolumab (trial 1) and of the copanlisib, nivolumab, and ipilimumab (trial 2) will be measured by ORR. ORR will be estimated with 95% confidence intervals.
Measured: Up to 24 months.
Clinical Benefit Rate (CBR) = (ORR + Stable Disease [SD] > 6 Months)
CBR will be estimated with 95% confidence intervals.
Measured: Up to 24 months.
Progression Free Survival
Will use the Kaplan-Meier method to estimate this distribution.
Measured: Up to 24 months.
Overall Survival
Will use the Kaplan-Meier method to estimate this distribution.
Measured: Up to 24 months.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Mar 2020
- Study start17 Jul 2020
- Primary completion1 Oct 2025
- Study completion6 May 2027 (estimated)
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.
- Other trials for Advanced Malignant Solid NeoplasmStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The 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
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 54 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Timothy A Yap, Principal investigator, University of Texas MD Anderson Cancer Center LAO
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04317105
- Sponsor's protocol ID
- NCI-2020-01917
- Other IDs
- NCI-2020-01917, NCI10221, 10221, 10221, UM1CA186688
- Status last verified
- Oct 2026
- First submitted
- 20 Mar 2020
- Last updated
- 27 Oct 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page.
Study at a glance
From the registry record, last updated by the sponsor on 27 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I/II Biomarker Driven Combination Trial of Copanlisib and Immune Checkpoint Inhibitors in Patients With Advanced Solid Tumors
- ClinicalTrials.gov ID
- NCT04317105
- Acronym / sponsor ID
- NCI-2020-01917
- Conditions
- Advanced Malignant Solid Neoplasm, Metastatic Malignant Solid Neoplasm, Unresectable Malignant Solid Neoplasm
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 54 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- 17 Jul 2020 (actual)
- Primary completion
- 1 Oct 2025 (actual)
- Study completion
- 6 May 2027 (estimated)
- First posted
- 23 Mar 2020 (actual)
- Results
- Posted 27 Oct 2026
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This phase I/II trial studies the side effects and best dose of copanlisib when given together with nivolumab and ipilimumab and to see how well they work in treating patients with solid cancers that may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced) and have changes in PIK3CA and PTEN genes. Copanlisib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Immunotherapy with monoclonal antibodies, such as nivolumab and ipilimumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. The addition of copanlisib to usual immunotherapy may work better in treating patients with solid cancers compared to usual immunotherapy alone.
Detailed description
PRIMARY OBJECTIVE:
- To evaluate safety and confirm the combination recommended phase 2 dose (RP2D) of the combination of copanlisib, nivolumab (and ipilimumab) in patients with molecularly-selected advanced solid tumors.
SECONDARY OBJECTIVES:
- To observe and record antitumor activity. II. To assess clinical benefit of copanlisib in combination with nivolumab (and ipilimumab) in patients with molecularly-selected advanced solid tumors, as measured by objective response (OR) = complete response (CR) + partial response (PR).
III. To assess overall duration of response (DoR), progression free survival (PFS), and overall survival (OS).
IV. To assess immune-modulatory changes associated with copanlisib-induced PI3K inhibition and combination of copanlisib and nivolumab (and ipilimumab).
- To correlate molecular alterations in the PI3K-AKT pathway and treatment induced immune-modulatory changes with objective response (OR).
EXPLORATORY OBJECTIVES:
- To perform molecular profiling assays on malignant and normal tissues, including, but not limited to, whole exome sequencing (WES), ribonucleic acid (RNA) sequencing, reverse phase protein array (RPPA), circulating tumor deoxyribonucleic acid (DNA) analysis, and immune profiling in order to:
Ia. Identify potential predictive and prognostic biomarkers beyond any genomic alteration by which treatment may be assigned; Ib. Identify resistance mechanisms using genomic DNA- and RNA-based assessment platforms.
II. To contribute genetic analysis data from de-identified biospecimens to Genomic Data Commons (GDC), a well annotated cancer molecular and clinical data repository, for current and future research.
III. To bank formalin-fixed, paraffin-embedded (FFPE) tissue, blood (for cell-free DNA analysis), and nucleic acids obtained from patients at the Early-Phase and Experimental Clinical Trials (EET) Biobank at Nationwide Children's Hospital.
OUTLINE: This is a phase I, dose-escalation study of copanlisib followed by a phase II study. Patients are assigned to 1 of 2 trials.
TRIAL I: Patients receive copanlisib hydrochloride intravenously (IV) over 1 hour on days 1, 8, and 15 of cycle 1. Beginning in cycle 2, patients also receive nivolumab IV over 60 minutes on day 1. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo an x-ray and/or computed tomography (CT) scan during screening and every 8 weeks, as well as a tumor biopsy at baseline, cycle 1 day 15, cycle 2 day 15, and every 3 weeks thereafter, and at disease progression. Patients also undergo blood sample collection at baseline, cycle 1 days 8 and 15, cycle 2 day 15, cycle 4 day 1 and disease progression. Patients undergo echocardiography (ECHO) during screening and as clinically indicated on study.
TRIAL II: Patients receive copanlisib hydrochloride IV over 1 hour on days 1, 8, and 15 of cycle 1. Beginning in cycle 2, patients also receive nivolumab IV over 60 minutes on day 1 and ipilimumab IV over 90 minutes every 8 weeks for 4 doses. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo an x-ray and/or CT scan during screening and every 8 weeks, as well as a tumor biopsy at baseline, cycle 1 day 15, cycle 2 day 15, and every 3 weeks thereafter, and at disease progression. Patients also undergo blood sample collection at baseline, cycle 1 days 8 and 15, cycle 2 day 15, cycle 4 day 1 and disease progression. Patients undergo ECHO during screening and as clinically indicated on study.
After completion of study treatment, patients are followed up at 30 days and then every 3-6 months for up to 2 years.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Trial I (copanlisib, nivolumab) | Experimental | Procedure: Biopsy Procedure, Procedure: Biospecimen Collection, Procedure: Computed Tomography, Drug: Copanlisib Hydrochloride, Procedure: Echocardiography Test, Biological: Nivolumab, Procedure: X-Ray ImagingPatients receive copanlisib hydrochloride IV over 1 hour on days 1, 8, and 15 of cycle 1. Beginning in cycle 2, patients also receive nivolumab IV over 60 minutes on day 1. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo an x-ray and/or CT scan during screening and every 8 weeks, as well as a tumor biopsy at baseline, cycle 1 day 15, cycle 2 day 15, and every 3 weeks thereafter, and at disease progression. Patients also undergo blood sample collection at baseline, cycle 1 days 8 and 15, cycle 2 day 15, cycle 4 day 1 and disease progression. Patients undergo ECHO during screening and as clinically indicated on study. |
| Trial II (copanlisib, nivolumab, ipilimumab) | Experimental | Procedure: Biopsy Procedure, Procedure: Biospecimen Collection, Procedure: Computed Tomography, Drug: Copanlisib Hydrochloride, Procedure: Echocardiography Test, Biological: Ipilimumab, Biological: Nivolumab, Procedure: X-Ray ImagingPatients receive copanlisib hydrochloride IV over 1 hour on days 1, 8, and 15 of cycle 1. Beginning in cycle 2, patients also receive nivolumab IV over 60 minutes on day 1 and ipilimumab IV over 90 minutes every 8 weeks for 4 doses. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo an x-ray and/or CT scan during screening and every 8 weeks, as well as a tumor biopsy at baseline, cycle 1 day 15, cycle 2 day 15, and every 3 weeks thereafter, and at disease progression. Patients also undergo blood sample collection at baseline, cycle 1 days 8 and 15, cycle 2 day 15, cycle 4 day 1 and disease progression. Patients undergo ECHO during screening and as clinically indicated on study. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (19 listed)
- Patients must have histologically confirmed malignancy that is metastatic or unresectable and for which standard curative measures do not exist or are no longer effective
- Patients must be >= 4 weeks beyond treatment with any chemotherapy or other investigational therapy to include hormonal, biological, or targeted agents; or at least 5 half-lives from hormonal, biological, or targeted agents, whichever is shorter at the time of treatment initiation
- Age >= 18 years. Because no dosing or adverse event data are currently available on the use of copanlisib in combination with nivolumab (and ipilimumab) in patients < 18 years of age, children are excluded from this study, but will be eligible for future pediatric trials
- Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1
- Absolute neutrophil count (ANC) >= 1,500 /mcL
Key exclusion criteria (23 listed)
- Patients who are receiving any other investigational agents
- Pregnant or breastfeeding women will be excluded from participation in this trial, as there is no significant clinical information regarding the effects of copanlisib, nivolumab, and ipilimumab on a fetus or newborn infant
- Known active hepatitis B or hepatitis C infection. All patients must be screened for hepatitis B virus (HBV) and hepatitis C virus (HCV) up to 28 days prior to study drug start using the routine hepatitis virus lab panel. Patients positive for hepatitis B virus surface antigen (HBsAg) and/or hepatitis B virus core antibody (HBcAb) will be eligible if they are negative for HBV DNA, these patients should receive prophylactic antiviral therapy. Patients positive for anti-HCV antibody will be eligible if they are negative for HCV RNA
- Human immunodeficiency virus (HIV)-infected (HIV1/2 antibody-positive) patients may participate IF they meet all the following eligibility requirements:
- Active infection requiring intravenous (IV) antibiotics or other uncontrolled intercurrent illness requiring hospitalization
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 |
|---|---|---|
| Biopsy ProcedureAlso: Biopsy, BIOPSY_TYPE, BxUndergo a tumor biopsy | Procedure or surgery | Trial I (copanlisib, nivolumab), Trial II (copanlisib, nivolumab, ipilimumab) |
| Biospecimen CollectionAlso: Biological Sample Collection, Biospecimen Collected, Sample Collection, Specimen CollectionUndergo blood sample collection | Procedure or surgery | Trial I (copanlisib, nivolumab), Trial II (copanlisib, nivolumab, ipilimumab) |
| Computed TomographyAlso: CAT, CAT Scan, Computed Axial Tomography, Computerized Axial TomographyUndergo a CT scan | Procedure or surgery | Trial I (copanlisib, nivolumab), Trial II (copanlisib, nivolumab, ipilimumab) |
| Copanlisib HydrochlorideAlso: 5-Pyrimidinecarboxamide, 2-Amino-N-(2,3-dihydro-7-methoxy-8-(3-(4-morpholinyl)propoxy)imidazo(1,2-C)quinazolin-5-yl)-, Hydrochloride (1:2), Aliqopa, BAY 80-6946 Dihydrochloride, BAY-80-6946 DihydrochlorideGiven IV | Drug | Trial I (copanlisib, nivolumab), Trial II (copanlisib, nivolumab, ipilimumab) |
| Echocardiography TestAlso: EC, EchocardiographyUndergo ECHO | Procedure or surgery | Trial I (copanlisib, nivolumab), Trial II (copanlisib, nivolumab, ipilimumab) |
| IpilimumabAlso: Anti-Cytotoxic T-Lymphocyte-Associated Antigen-4 Monoclonal Antibody, BMS 734016, BMS-734016, BMS734016Given IV | Biological | Trial II (copanlisib, nivolumab, ipilimumab) |
| NivolumabAlso: ABP 206, BCD-263, BMS 936558, BMS-936558Given IV | Biological | Trial I (copanlisib, nivolumab), Trial II (copanlisib, nivolumab, ipilimumab) |
| X-Ray ImagingAlso: Conventional X-Ray, Diagnostic Radiology, Medical Imaging, X-Ray, Plain film radiographsUndergo an x-ray | Procedure or surgery | Trial I (copanlisib, nivolumab), Trial II (copanlisib, nivolumab, ipilimumab) |
Primary outcome
Number of Patients With Dose Limiting Toxicities as a Measure of Safety Profile to Determine the Recommended Phase 2 Dose (RP2D).
Time frame: The DLT monitoring time frame consisted of the first and second 28-day cycles.
A DLT was evaluated according to the NCI CTCAE v5.0 and defined as Grade 4 neutropenia lasting greater than 7 days, febrile neutropenia, neutropenic infection, greater than or equal to grade 3 thrombocytopenia with bleeding, grade 4 thrombocytopenia, grade 4 anemia, non-hematologic greater than or equal to grade 4 toxicities, significant increase in QTc prolongation compared to baseline, grade 3 skin rash or diarrhea despite intervention, any any event that is greater than at baseline and is unacceptable according to the investigator and safety review committee.
4 secondary outcomes
Objective Response Rate (ORR)= Complete Response [CR] + Partial Response [PR])
Time frame: Up to 24 months.
Clinical Benefit Rate (CBR) = (ORR + Stable Disease [SD] > 6 Months)
Time frame: Up to 24 months.
Progression Free Survival
Time frame: Up to 24 months.
Overall Survival
Time frame: Up to 24 months.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Oct 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Yes. NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page.
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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.
Timothy A Yap principal investigator
University of Texas MD Anderson Cancer Center LAO
6 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Biopsy Procedure, Biospecimen Collection and Computed Tomography in people with Advanced Malignant Solid Neoplasm and Metastatic Malignant Solid Neoplasm, run by National Cancer Institute (NCI) at 6 sites in 2 countries.
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 19 inclusion and 23 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: under way, not looking for participants, as of the sponsor's last update on 27 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in United States, Canada. 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 27 Oct 2026). 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 Patients With Dose Limiting Toxicities as a Measure of Safety Profile to Determine the Recommended Phase 2 Dose (RP2D). (time frame: The DLT monitoring time frame consisted of the first and second 28-day cycles.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 27 Oct 2026.