Active, not recruitingNCT03939897Updated Sep 8, 2026Results posted

Testing the Addition of Copanlisib to Usual Treatment (Fulvestrant and Abemaciclib) in Metastatic Breast Cancer

A Phase 1 interventional study of Abemaciclib and Biopsy Procedure in Anatomic Stage IV Breast Cancer AJCC v8, Metastatic Breast Carcinoma and Metastatic HER2-Negative Breast Carcinoma, sponsored by National Cancer Institute (NCI). Active, not recruiting at 14 sites in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-09-08.

Sponsored by National Cancer Institute (NCI) · Phase 1, Interventional, and Treatment

Phase: Phase 1
Study type: Interventional
Enrollment: 24
Allocation: Randomized
Ages: 18 Years and older
Sex: All

Study summary

This phase I trial studies the effects (good and bad) of adding copanlisib to the usual therapy of fulvestrant and abemaciclib in treating patients with hormone receptor positive and HER2 negative breast cancer that has spread from where it first started (breast) to other places in the body (metastatic). Some breast cancer cells have receptors for the hormones estrogen or progesterone. These cells are hormone receptor positive and they need estrogen or progesterone to grow. This can affect how the cancer is treated. Hormone therapy using fulvestrant may fight breast cancer by blocking the use of estrogen by the tumor cells. Abemaciclib and copanlisib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Adding copanlisib to the usual therapy of fulvestrant and abemaciclib may work better than giving fulvestrant and abemaciclib alone in treating patients with breast cancer.

Read the detailed description

PRIMARY OBJECTIVES:

I. To evaluate the safety profile of fulvestrant + abemaciclib + copanlisib hydrochloride (copanlisib) (FAC) and determine the recommended phase 2 dose (RP2D).

SECONDARY OBJECTIVES:

I. To assess the objective response rate (ORR = partial response [PR] + complete response [CR]) and clinical benefit rate (CBR = PR + CR + stable disease [SD] >= 6 months) of FAC and medium progression free survival (PFS) with FAC.

EXPLORATORY OBJECTIVES:

I. To assess whether triplet therapy with FAC inhibits AKT phosphorylation, reduces cyclin D1, and inhibits Rb phosphorylation.

II. To assess whether the combination of abemaciclib and fulvestrant affect the copanlisib pharmacokinetics (PK).

III. To assess the objective response rate (ORR), clinical benefit rate (CBR) and median PFS in the following molecularly defined subgroups treated with FAC such as mutations in genes in the PI3K pathway (PIK3CA, AKT, PTEN etc), ESR1, TP53, or PTEN IHC loss vs not.

IV. To assess baseline and treatment induced changes in various cancer associated pathways, including but not limited to PI3K, MAPK, ER, cyclins, CDKs and CDK inhibitors; and to correlate with treatment response and progression.

V. To correlate baseline and treatment induced changes in breast cancer intrinsic subtypes (PAM50), and PI3K messenger ribonucleic acid (mRNA) signature and expression of candidate genes with treatment response and benefit from adding copanlisib.

VI. To evaluate ctDNA mutations at baseline and over time for response predictors at baseline, and clonal evolution associated with treatment.

VII. To correlate ctDNA mutation profiles with tumor sequencing, and correlate baseline ctDNA mutations, particularly in components of the PI3K pathway with treatment response, and correlate early changes in ctDNA variant allele frequencies (VAFs) with PFS, assess emergent resistant mutations at progression.

VIII. To assess resistance mechanisms to FAC at baseline and at disease progression.

IX. To examine the molecular effects of FAC on tumor and circulating markers. X. To analyze tumor infiltrating lymphocytes at baseline, during treatment, and at disease progression.

OUTLINE: This is a phase I two part, dose-escalation study of copanlisib hydrochloride and abemaciclib.

PHASE I (PART A): Patients receive copanlisib hydrochloride intravenously (IV) over 1 hour on days 1, 8, and 15 or days 1 and 15 (depending on dose level) and abemaciclib orally (PO) twice daily (BID) on on days 2-28 of cycle 1 and on days 1-28 of subsequent cycles. Patients also receive fulvestrant intramuscularly (IM) on days 2 and 16 of cycle 1, and on day 1 of subsequent cycles. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo an echocardiography (ECHO) or multigated acquisition (MUGA) scan during screening. Patients also undergo blood sample collection pre-treatment, cycle 1 days 1, 8, 15, and 22, cycle 2 day 1, cycle 4 day 1, cycle 7 day 1, and then every 3 cycles thereafter and at time of progression. Patients undergo tissue biopsy pre-treatment and optionally on cycle 1 day 15 and at the time of progression. Patients also undergo imaging at screening and at the completion of cycle 3, then every 3 cycles thereafter.

PHASE I (PART B): Patients receive copanlisib hydrochloride IV over 1 hour on days 1, 8, and 15 or days 1 and 15 (depending on dose level) and abemaciclib PO twice daily BID for 5 days each week (2 days off). Patients also receive fulvestrant IM on days 2 and 16 of cycle 1, and on day 1 of subsequent cycles. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo an ECHO or MUGA scan during screening. Patients also undergo blood sample collection pre-treatment, cycle 1 days 1, 8, 15, and 22, cycle 2 day 1, cycle 4 day 1, cycle 7 day 1, and then every 3 cycles thereafter and at time of progression. Patients undergo tissue biopsy pre-treatment and optionally on cycle 1 day 15 and at the time of progression. Patients also undergo imaging at screening and at the completion of cycle 3, then every 3 cycles thereafter.

After completion of study treatment, patients are followed up every 3 months for 5 years.

* As of November 2023, Bayer has decided to voluntarily withdraw the NDA for copanlisib, phase II portion removed.

Conditions studied

Anatomic Stage IV Breast Cancer AJCC v8
Metastatic Breast Carcinoma
Metastatic HER2-Negative Breast Carcinoma
Metastatic Hormone Receptor-Positive Breast Carcinoma
Recurrent Breast Carcinoma

Browse trials for

Breast Neoplasms 12,544

In context

Breast Neoplasms

12,544 studies on the registry are indexed under Breast Neoplasms; 2,892 are open to participants now.

This study's enrollment of 24 is below the median of 72 across 9,303 interventional studies indexed under Breast Neoplasms.

Browse Breast Neoplasms studies →

Lead sponsor

National Cancer Institute (NCI) is the lead sponsor of 3,506 studies on the registry; 334 are open to participants now.

Of its 402 completed or terminated interventional studies of FDA-regulated products, 365 (91%) have results posted.

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 18 Years and older
Sexes eligible: All
Accepts healthy volunteers: No

Inclusion criteria

Patients must have histologically or cytologically confirmed ER and/or PR positive, HER2 negative or non-amplified breast cancer that is stage IV, with measurable or non-measurable disease. ER/PR positivity is defined as at least 1% positive or an Allred score of at least 3. HER2 status is defined per the 2018 American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) guideline
All patients must agree to provide archival tumor material for research and must agree to undergo research tumor biopsy before treatment if presence of easily accessible lesions (judged by the treating physician). For patients with bone only disease, or patients without easily accessible lesions for the baseline research biopsy, availability of archival tumor material (2 x 4-5 micron section unstained slides, plus 15-20 x 10 micron section unstained slides or a tumor rich block) from previous breast cancer diagnosis or treatment is required for central PTEN and PIK3CA analysis
No more than 1 prior chemotherapy in the metastatic setting. There is no limit on prior lines of endocrine therapy. (For patients enrolling to the phase 1 portion of the study, prior fulvestrant, CDK4/6 inhibitor, and everolimus is allowed)
For patients enrolling to the randomized phase 2 portion of this study, demonstrated resistance to prior endocrine therapy in the metastatic setting is required; this is defined as:
- Progressed on prior endocrine therapy in the metastatic setting or,
- Relapsed on adjuvant endocrine therapy or,
- Relapsed within 12 months of completing adjuvant endocrine therapy or,
- If received adjuvant CDK4/6 inhibitor, relapsed at least 2 years after completion of adjuvant CDK4/6 inhibitor
Washout from prior systemic anti-cancer therapy of at least 3 weeks from chemotherapy or 5 half-lives from oral targeted drugs, and treatment related adverse events recovered to grade 1 (except for alopecia) before the start of study treatment. Washout from prior radiation therapy of at least 2 weeks before the start of the study treatment. Washout from prior endocrine therapy is not required
Age >= 18 years. Because no dosing or adverse event (AE) data are currently available on the use of copanlisib in combination with abemaciclib and fulvestrant in patients \< 18 years of age, and because breast cancer is rare in children, children are excluded from this study
Eastern Cooperative Oncology Group (ECOG) performance status =\< 2 (Karnofsky >= 60%)
Leukocytes >= 3,000/mcL (no more than 7 days before starting study treatment)
Absolute neutrophil count >= 1,500/mcL (no more than 7 days before starting study treatment)
Platelets >= 100,000/mcL (no more than 7 days before starting study treatment)
Hemoglobin >= 8.0 g/dL (no more than 7 days before starting study treatment)
Total bilirubin =\< 1.5 x institutional upper limit of normal (=\< 3 x institutional upper limit of normal for patients with Gilbert syndrome) (no more than 7 days before starting study treatment)
Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =\< 3 x institutional upper limit of normal (=\< 5 x institutional upper limit of normal for patients with liver involvement) (no more than 7 days before starting study treatment)
Glomerular filtration rate >= 30 mL/min according to the Modification of Diet in Renal Disease (MDRD) abbreviated formula (no more than 7 days before starting study treatment)
Lipase =\< 1.5 x upper limit of normal (ULN) (no more than 7 days before starting study treatment)
International normalized rate (INR) and partial thromboplastin time (PTT) =\< 1.5 x ULN (except those on anti-coagulation therapy) (no more than 7 days before starting study treatment)
Hemoglobin (Hb)A1c =\< 8.5% or fasting glucose =\< 120 mg/dL on at least 2 occasions within 14 days prior to registration if diabetic (no more than 7 days before starting study treatment)
Left ventricular ejection fraction (LVEF) >= 50%
Patients may be postmenopausal or premenopausal women on or planned to receive gonadotropin-releasing hormone (GnRH) agonist
The effects of copanlisib on the developing human fetus are unknown. For this reason and because maternal toxicity, developmental toxicity and teratogenic effects have been observed in nonclinical studies and PI3K inhibitors as well as other therapeutic agents used in this trial are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 6 months after the last dose of copanlisib. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 6 months after completion of copanlisib administration
Ability to understand and willing to sign a written informed consent document (or legally authorized representative, if applicable). Patient must agree to research team access to prior breast cancer diagnosis and treatment records, as well as reports of clinical tumor and blood sequencing results
Patients with a history of treated brain metastases are allowed in the phase I portion of the trial provided there is no disease progression symptomatically and by imaging within 28 days prior to registration AND if the patient is off steroids
Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial

Exclusion criteria

Exclusion Criteria:

For patients enrolling to the randomized phase 2 portion of the study, prior treatment with a CDK4/6 inhibitor or fulvestrant, or a PI3K inhibitor in the metastatic setting is not allowed
Patients who have had chemotherapy within 3 weeks or radiotherapy within 2 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study
Patients who are receiving any other investigational agents
Immunosuppressive therapy is not allowed while on study
Receiving anti-arrhythmic therapy (beta blockers or digoxin are permitted)
History of allergic reactions attributed to compounds of similar chemical or biologic composition to copanlisib, PI3K inhibitors, or other agents used in study
For the randomized phase 2 portion of the study, patients with brain metastasis or a history of brain metastasis are not eligible
- For the phase 1 portion of the study, patients with progressive brain metastases should be excluded because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events (AEs)
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) are not permitted from 14 days prior to enrollment until the end of the study
- It is important to regularly consult a frequently-updated medical reference for a list of drugs to avoid or minimize use of. As part of the enrollment/informed consent procedures, the patient will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the patient is considering a new over-the-counter medicine or herbal product
Systemic corticosteroid therapy at a daily dose higher than 15 mg prednisone or equivalent is not permitted while on study. Previous corticosteroid therapy must be stopped or reduced to the allowed dose at least 7 days prior to the computed tomography (CT)/magnetic resonance imaging (MRI) screening. If a patient is on chronic corticosteroid therapy, corticosteroids should be de-escalated to the maximum allowed dose before the screening. Patients may be using topical or inhaled corticosteroids. Short-term (up to 7 days) systemic corticosteroids above 15 mg prednisolone or equivalent will be allowed for the management of acute conditions (e.g., treatment non-infectious pneumonitis)
Major surgical procedure or significant traumatic injury (as judged by the investigator) within 28 days before start of treatment, or have not recovered from major side effects, open biopsy within 7 days before start of treatment
Uncontrolled intercurrent illness, including but not limited to, symptomatic congestive heart failure (> New York Heart Association [NYHA] class 2), unstable angina pectoris, new-onset angina, uncontrolled hypertension despite optimal medical management, seizure disorder requiring medication, or psychiatric illness/social situations that would limit compliance with study requirements
Myocardial infarction \< 6 months before start of treatment
Arterial or venous thrombotic or embolic events such as cerebrovascular accident (including transient ischemic attacks), deep vein thrombosis or pulmonary embolism within 3 months before the start of study medication
The patient has a personal history of any of the following conditions: syncope of cardiovascular etiology, ventricular arrhythmia of pathological origin (including, but not limited to, ventricular tachycardia and ventricular fibrillation), or sudden cardiac arrest
Proteinuria >= grade 3 as assessed by a 24-hour (h) protein quantification or estimated by urine protein: creatinine ratio > 3.5 on a random urine sample
History of bleeding diathesis. Any hemorrhage or bleeding event >= grade 3 within 4 weeks prior to the start of study medication
History or concurrent condition of interstitial lung disease of any severity and/or severely impaired lung function
History of having received an allogeneic bone marrow or organ transplant
Patients with non-healing wound, ulcer, or bone fracture not due to breast cancer
Patients with active, clinically serious infections > grade 2 (Common Terminology Criteria for Adverse Events [CTCAE] version [v] 5.0)
Patients with HbA1c > 8.5% at screening
Concurrent diagnosis of pheochromocytoma
Has undergone blood or platelet transfusion \< 7 days prior to start of treatment
Pregnant women are excluded from this study because copanlisib is a PI3K inhibitor agent with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with copanlisib, breastfeeding should be discontinued if the mother is treated with copanlisib. These potential risks may also apply to other agents used in this study
Hepatitis B (HBV) or hepatitis C (HCV). All patients must be screened for HBV and HCV up to 28 days prior to study drug start using the routine hepatitis virus lab panel. Patients positive for hepatitis B surface antigen (HBsAg) and/or hepatitis B 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
HIV positive patients on combination antiretroviral agents that are strong CYP3A4 inhibitors or inducers and who are unwilling or unable to change to antiretroviral therapies without such interactions are ineligible because of the potential for pharmacokinetic interactions with copanlisib, abemaciclib, and fulvestrant. Appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated
Patients with history of, or current autoimmune disease are not eligible
History of major surgical resection involving the stomach or small bowel, or preexisting Crohn's disease or ulcerative colitis or a preexisting chronic condition resulting in baseline grade 2 or higher diarrhea

Study design

Phase: Phase 1
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Sequential assignment
Masking: None (open label)
Enrollment: 24 participants (actual)

Study arms

Experimental
Phase I Part A Dose 1 (copanlisib, abemaciclib, fulvestrant)
Patients receive 45 mg copanlisib hydrochloride IV over 1 hour on days 1 and 15 and 100 mg abemaciclib PO BID on days 2-28 of cycle 1 and on days 1-28 of subsequent cycles. Patients also receive 500 mg fulvestrant IM on days 2 and 16 of cycle 1, and on day 1 of subsequent cycles. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo an ECHO or MUGA scan during screening. Patients also undergo blood sample collection pre-treatment, cycle 1 days 1, 8, 15, and 22, cycle 2 day 1, cycle 4 day 1, cycle 7 day 1, and then every 3 cycles thereafter and at time of progression. Patients undergo tissue biopsy pre-treatment and optionally on cycle 1 day 15 and at the time of progression. Patients also undergo imaging at screening and at the completion of cycle 3, then every 3 cycles thereafter.
Drug: Abemaciclib · Procedure: Biopsy Procedure · Procedure: Biospecimen Collection · Drug: Copanlisib Hydrochloride · Procedure: Diagnostic Imaging Testing · Procedure: Echocardiography Test · Drug: Fulvestrant · Procedure: Multigated Acquisition Scan
Experimental
Phase I Part A Dose 2 (copanlisib, abemaciclib, fulvestrant)
Patients receive 45 mg copanlisib hydrochloride IV over 1 hour on days 1, 8, and 15 and 150 mg abemaciclib PO twice daily BID for 5 days each week (2 days off). Patients also receive f500 mg fulvestrant IM on days 2 and 16 of cycle 1, and on day 1 of subsequent cycles. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo an ECHO or MUGA scan during screening. Patients also undergo blood sample collection pre-treatment, cycle 1 days 1, 8, 15, and 22, cycle 2 day 1, cycle 4 day 1, cycle 7 day 1, and then every 3 cycles thereafter and at time of progression. Patients undergo tissue biopsy pre-treatment and optionally on cycle 1 day 15 and at the time of progression. Patients also undergo imaging at screening and at the completion of cycle 3, then every 3 cycles thereafter.
Drug: Abemaciclib · Procedure: Biopsy Procedure · Procedure: Biospecimen Collection · Drug: Copanlisib Hydrochloride · Procedure: Diagnostic Imaging Testing · Procedure: Echocardiography Test · Drug: Fulvestrant · Procedure: Multigated Acquisition Scan
Experimental
Phase I Part B Dose 1b (copanlisib, abemaciclib, fulvestrant)
Patients receive 45 mg copanlisib hydrochloride IV over 1 hour on days 1 and 15 and 100 mg abemaciclib PO twice daily BID for 5 days each week (2 days off). Patients also receive 500 fulvestrant IM on days 2 and 16 of cycle 1, and on day 1 of subsequent cycles. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo an ECHO or MUGA scan during screening. Patients also undergo blood sample collection pre-treatment, cycle 1 days 1, 8, 15, and 22, cycle 2 day 1, cycle 4 day 1, cycle 7 day 1, and then every 3 cycles thereafter and at time of progression. Patients undergo tissue biopsy pre-treatment and optionally on cycle 1 day 15 and at the time of progression. Patients also undergo imaging at screening and at the completion of cycle 3, then every 3 cycles thereafter.
Drug: Abemaciclib · Procedure: Biopsy Procedure · Procedure: Biospecimen Collection · Drug: Copanlisib Hydrochloride · Procedure: Diagnostic Imaging Testing · Procedure: Echocardiography Test · Drug: Fulvestrant · Procedure: Multigated Acquisition Scan
Active comparator
Phase I Part B Dose 2b (copanlisib, abemaciclib, fulvestrant)
Patients receive 45 mg copanlisib hydrochloride IV over 1 hour on days 1, 8, and 15 and 100 mg abemaciclib PO twice daily BID for 5 days each week (2 days off). Patients also receive 500 mg fulvestrant IM on days 2 and 16 of cycle 1, and on day 1 of subsequent cycles. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo an ECHO or MUGA scan during screening. Patients also undergo blood sample collection pre-treatment, cycle 1 days 1, 8, 15, and 22, cycle 2 day 1, cycle 4 day 1, cycle 7 day 1, and then every 3 cycles thereafter and at time of progression. Patients undergo tissue biopsy pre-treatment and optionally on cycle 1 day 15 and at the time of progression. Patients also undergo imaging at screening and at the completion of cycle 3, then every 3 cycles thereafter.
Drug: Abemaciclib · Procedure: Biopsy Procedure · Procedure: Biospecimen Collection · Drug: Copanlisib Hydrochloride · Procedure: Diagnostic Imaging Testing · Procedure: Echocardiography Test · Drug: Fulvestrant · Procedure: Multigated Acquisition Scan

Interventions

DrugAbemaciclib
Given PO
Also known as: LY 2835219, LY-2835219, LY2835219, Verzenio
ProcedureBiopsy Procedure
Undergo tissue biopsy
Also known as: Biopsy, BIOPSY_TYPE, Bx
ProcedureBiospecimen Collection
Undergo blood sample collection
Also known as: Biological Sample Collection, Biospecimen Collected, Sample Collection, Specimen Collection
DrugCopanlisib Hydrochloride
Given IV
Also known as: 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, Copanlisib Dihydrochloride
ProcedureDiagnostic Imaging Testing
Undergo imaging
Also known as: Diagnostic Imaging, Medical Imaging
ProcedureEchocardiography Test
Undergo ECHO
Also known as: EC, Echocardiography
DrugFulvestrant
Given IM
Also known as: Faslodex, Faslodex(ICI 182,780), ICI 182,780, ICI 182780, ICI-182780, ICI182780, ZD 9238, ZD-9238, ZD9238
ProcedureMultigated Acquisition Scan
Undergo MUGA
Also known as: Blood Pool Scan, Equilibrium Radionuclide Angiography, Gated Blood Pool Imaging, Gated Heart Pool Scan, MUGA, MUGA Scan, Multi-Gated Acquisition Scan, Radionuclide Ventriculogram Scan, Radionuclide Ventriculography, RNV Scan, RNVG, SYMA Scanning, Synchronized Multigated Acquisition Scanning

What researchers measure

Primary outcomes

Dose-limiting Toxicity (DLT)
DLT will be determined based on the incidence, intensity and duration of adverse events (AEs) that are related to the drug combinations and occur within 28 days of drug administration. The severity of AEs will be graded according to National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0. AEs will be summarized by counts and percentages, overall as well as by dose levels and by patient characteristics.
Time frame: Up to 28 days from drug administration

Secondary outcomes

Progression-free Survival (PFS)
Radiographic disease recurrence/progression will be assessed using the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria. Will be estimated by the Kaplan-Meier (KM) product limit method and survival difference will be compared between the two arms by stratified log rank test. Hazard ratio with 95% confidence interval (CI) will be estimated between the two arms from the stratified Cox proportional hazard model, without and with adjustment for patient characteristics.
Time frame: Time from randomization to the event of disease recurrence/progression or death due to any cause, assessed up to 4 years
Objective Response Rate (ORR)
Will be defined as the proportion of response-evaluable patients who achieve complete response (CR) or partial response (PR) and assessed by RECIST 1.1 criteria. Will be estimated with a 95% exact CI and difference between the two arms will be compared by Fisher's exact test. Raw and adjusted odds ratio (OR) will be derived with 95% CI from logistic regression without and with adjustment for patient characteristics.
Time frame: Time from randomization to the event of disease recurrence/progression or death due to any cause, assessed up to 4 years
Clinical Benefit Rate
Will be defined as the proportion of response-evaluable patients who achieve CR or PR or stable disease (SD) for at least 6 months and assessed by RECIST 1.1 criteria. Will be estimated with a 95% exact CI and difference between the two arms will be compared by Fisher's exact test. Raw and adjusted OR will be derived with 95% CI from logistic regression without and with adjustment for patient characteristics
Time frame: Time from randomization to the event of disease recurrence/progression or death due to any cause, assessed up to 4 years
Overall Survival
Will be assessed by RECIST 1.1 criteria. Will be estimated by the KM product limit method and survival difference will be compared between the two arms by stratified log rank test. Hazard ratio with 95% CI will be estimated between the two arms from the stratified Cox proportional hazard model, without and with adjustment for patient characteristics.
Time frame: Time of randomization to time of death due to any cause or latest follow-up, whichever earlier, assessed up to 4 years

Results

Posted Jul 30, 2024

Participant flow

Participant flow — Overall Study
Milestone	Phase I Part A Dose Level 1 (Copanlisib, Abemaciclib, Fulvestrant)	Phase I Part A Dose Level 2 (Copanlisib, Abemaciclib, Fulvestrant)	Phase I Part B Dose Level 1b (Copanlisib, Abemaciclib, Fulvestrant)	Phase I Part B Dose Level 2b (Copanlisib, Abemaciclib, Fulvestrant)
Started	7	3	7	7
Completed	7	3	7	7
Not completed	0	0	0	0

Outcome measures

PrimaryDose-limiting Toxicity (DLT)

DLT will be determined based on the incidence, intensity and duration of adverse events (AEs) that are related to the drug combinations and occur within 28 days of drug administration. The severity of AEs will be graded according to National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0. AEs will be summarized by counts and percentages, overall as well as by dose levels and by patient characteristics.

Time frame:: Up to 28 days from drug administration
Reported as:: Count of participants · Participants

Dose-limiting Toxicity (DLT)
Participants	Phase I Part A Dose Level 1 (Copanlisib, Abemaciclib, Fulvestrant)	Phase I Part A Dose Level 2 (Copanlisib, Abemaciclib, Fulvestrant)	Phase I Part B Dose Level 1b (Copanlisib, Abemaciclib, Fulvestrant)	Phase I Part B Dose Level 2b (Copanlisib, Abemaciclib, Fulvestrant)
Dose-limiting Toxicity (DLT)	1	2	1	2

SecondaryProgression-free Survival (PFS)

Radiographic disease recurrence/progression will be assessed using the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria. Will be estimated by the Kaplan-Meier (KM) product limit method and survival difference will be compared between the two arms by stratified log rank test. Hazard ratio with 95% confidence interval (CI) will be estimated between the two arms from the stratified Cox proportional hazard model, without and with adjustment for patient characteristics.

Time frame:: Time from randomization to the event of disease recurrence/progression or death due to any cause, assessed up to 4 years
Reported as:: Median · months

Progression-free Survival (PFS)
months	Phase I Part A Dose Level 1 (Copanlisib, Abemaciclib, Fulvestrant)	Phase I Part A Dose Level 2 (Copanlisib, Abemaciclib, Fulvestrant)	Phase I Part B Dose Level 1b (Copanlisib, Abemaciclib, Fulvestrant)	Phase I Part B Dose Level 2b (Copanlisib, Abemaciclib, Fulvestrant)
Progression-free Survival (PFS)	5.9 (2.5 to 14.8)	7.9 (2.3 to NA)	19.3 (2.8 to NA)	18.7 (1.8 to NA)

Statistical analysis

Phase I Part A Dose Level 1 (Copanlisib, Abemaciclib, Fulvestrant) vs Phase I Part A Dose Level 2 (Copanlisib, Abemaciclib, Fulvestrant) vs Phase I Part B Dose Level 1b (Copanlisib, Abemaciclib, Fulvestrant) vs Phase I Part B Dose Level 2b (Copanlisib, Abemaciclib, Fulvestrant) · Log Rank · p = 0.5060

SecondaryObjective Response Rate (ORR)

Will be defined as the proportion of response-evaluable patients who achieve complete response (CR) or partial response (PR) and assessed by RECIST 1.1 criteria. Will be estimated with a 95% exact CI and difference between the two arms will be compared by Fisher's exact test. Raw and adjusted odds ratio (OR) will be derived with 95% CI from logistic regression without and with adjustment for patient characteristics.

Time frame:: Time from randomization to the event of disease recurrence/progression or death due to any cause, assessed up to 4 years
Reported as:: Count of participants · Participants

Objective Response Rate (ORR)
Participants	Phase I Part A Dose Level 1 (Copanlisib, Abemaciclib, Fulvestrant)	Phase I Part A Dose Level 2 (Copanlisib, Abemaciclib, Fulvestrant)	Phase I Part B Dose Level 1b (Copanlisib, Abemaciclib, Fulvestrant)	Phase I Part B Dose Level 2b (Copanlisib, Abemaciclib, Fulvestrant)
Objective Response Rate (ORR)	1	0	2	2

SecondaryClinical Benefit Rate

Will be defined as the proportion of response-evaluable patients who achieve CR or PR or stable disease (SD) for at least 6 months and assessed by RECIST 1.1 criteria. Will be estimated with a 95% exact CI and difference between the two arms will be compared by Fisher's exact test. Raw and adjusted OR will be derived with 95% CI from logistic regression without and with adjustment for patient characteristics

Time frame:: Time from randomization to the event of disease recurrence/progression or death due to any cause, assessed up to 4 years
Reported as:: Count of participants · Participants

Clinical Benefit Rate
Participants	Phase I Part A Dose 1 (Copanlisib, Abemaciclib, Fulvestrant)	Phase I Part A Dose 2 (Copanlisib, Abemaciclib, Fulvestrant)	Phase I Part B Dose 1b (Copanlisib, Abemaciclib, Fulvestrant)	Phase I Part B Dose 2b (Copanlisib, Abemaciclib, Fulvestrant)
Clinical Benefit Rate	3	0	3	2

SecondaryOverall Survival

Will be assessed by RECIST 1.1 criteria. Will be estimated by the KM product limit method and survival difference will be compared between the two arms by stratified log rank test. Hazard ratio with 95% CI will be estimated between the two arms from the stratified Cox proportional hazard model, without and with adjustment for patient characteristics.

Time frame:: Time of randomization to time of death due to any cause or latest follow-up, whichever earlier, assessed up to 4 years
Reported as:: Median · months

Overall Survival
months	Phase I Part A Dose Level 1 (Copanlisib, Abemaciclib, Fulvestrant)	Phase I Part A Dose Level 2 (Copanlisib, Abemaciclib, Fulvestrant)	Phase I Part B Dose Level 1b (Copanlisib, Abemaciclib, Fulvestrant)	Phase I Part B Dose Level 2b (Copanlisib, Abemaciclib, Fulvestrant)
Overall Survival	14.8 (2.5 to NA)	12.2 (2.3 to NA)	NA (20.1 to NA)	NA (3.6 to NA)

Statistical analysis

Phase I Part A Dose Level 1 (Copanlisib, Abemaciclib, Fulvestrant) vs Phase I Part A Dose Level 2 (Copanlisib, Abemaciclib, Fulvestrant) vs Phase I Part B Dose Level 1b (Copanlisib, Abemaciclib, Fulvestrant) vs Phase I Part B Dose Level 2b (Copanlisib, Abemaciclib, Fulvestrant) · Log Rank · p = 0.2989

Adverse events

Collected over Adverse events (AEs) were collected from start of treatment through the end of treatment visit. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 126 days (full range 28-710 days). All-cause mortality was collected from start of treatment to death due to any cause or latest follow-up, whichever earlier. Overall median length of follow-up was 439 days (full range 66-1198 days).. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
Phase I Part A Dose Level 1 (Copanlisib, Abemaciclib, Fulvestrant)	5/7 (71.4%)	2/7 (28.6%)	7/7 (100%)
Phase I Part A Dose Level 2 (Copanlisib, Abemaciclib, Fulvestrant)	3/3 (100%)	3/3 (100%)	3/3 (100%)
Phase I Part B Dose Level 1b (Copanlisib, Abemaciclib, Fulvestrant)	2/7 (28.6%)	4/7 (57.1%)	7/7 (100%)
Phase I Part B Dose Level 2b (Copanlisib, Abemaciclib, Fulvestrant)	2/7 (28.6%)	5/7 (71.4%)	7/7 (100%)

Most frequent serious events

Showing 10 of 24

Most frequent serious events
Event	Phase I Part A Dose Level 1 (Copanlisib, Abemaciclib, Fulvestrant)	Phase I Part A Dose Level 2 (Copanlisib, Abemaciclib, Fulvestrant)	Phase I Part B Dose Level 1b (Copanlisib, Abemaciclib, Fulvestrant)	Phase I Part B Dose Level 2b (Copanlisib, Abemaciclib, Fulvestrant)
SyncopeNervous system disorders	0/7	2/3	0/7	0/7
VomitingGastrointestinal disorders	1/7	1/3	0/7	0/7
Lung InfectionInfections and infestations	0/7	1/3	0/7	1/7
PneumonitisRespiratory, thoracic and mediastinal disorders	0/7	1/3	0/7	2/7
Atrial fibrillationCardiac disorders	0/7	0/3	0/7	1/7
Heart failureCardiac disorders	0/7	0/3	0/7	1/7
DysphagiaGastrointestinal disorders	0/7	0/3	1/7	0/7
NauseaGastrointestinal disorders	1/7	0/3	0/7	0/7
Obstruction gastricGastrointestinal disorders	1/7	0/3	0/7	0/7
Death NOSGeneral disorders	0/7	0/3	0/7	1/7

Most frequent other events

Showing 10 of 145

Most frequent other events
Event	Phase I Part A Dose Level 1 (Copanlisib, Abemaciclib, Fulvestrant)	Phase I Part A Dose Level 2 (Copanlisib, Abemaciclib, Fulvestrant)	Phase I Part B Dose Level 1b (Copanlisib, Abemaciclib, Fulvestrant)	Phase I Part B Dose Level 2b (Copanlisib, Abemaciclib, Fulvestrant)
AnemiaBlood and lymphatic system disorders	7/7	1/3	4/7	6/7
DiarrheaGastrointestinal disorders	6/7	3/3	5/7	7/7
NauseaGastrointestinal disorders	6/7	3/3	5/7	5/7
FatigueGeneral disorders	5/7	3/3	4/7	7/7
ALT increasedInvestigations	6/7	1/3	4/7	3/7
Lymphocyte count decreasedInvestigations	6/7	0/3	2/7	5/7
White blood cell decreasedInvestigations	6/7	1/3	3/7	6/7
HypertensionVascular disorders	4/7	0/3	4/7	6/7
Mucositis oralGastrointestinal disorders	1/7	1/3	1/7	5/7
Creatinine increasedInvestigations	2/7	1/3	3/7	5/7

Baseline characteristics

There were not any subjects enrolled in the Phase II portion of the trial.

Age, Continuous
Age, Continuous(years)	Phase I Part A Dose Level 1 (Copanlisib, Abemaciclib, Fulvestrant)	Phase I Part A Dose Level 2 (Copanlisib, Abemaciclib, Fulvestrant)	Phase I Part B Dose Level 1b (Copanlisib, Abemaciclib, Fulvestrant)	Phase I Part B Dose Level 2b (Copanlisib, Abemaciclib, Fulvestrant)	Total
Median	58 (44 to 68)	62 (59 to 69)	56 (40 to 68)	63 (42 to 78)	59 (40 to 78)

Sex: Female, Male
Sex: Female, Male(Participants)	Phase I Part A Dose Level 1 (Copanlisib, Abemaciclib, Fulvestrant)	Phase I Part A Dose Level 2 (Copanlisib, Abemaciclib, Fulvestrant)	Phase I Part B Dose Level 1b (Copanlisib, Abemaciclib, Fulvestrant)	Phase I Part B Dose Level 2b (Copanlisib, Abemaciclib, Fulvestrant)	Total
Female	7	2	7	7	23
Male	0	1	0	0	1

Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)	Phase I Part A Dose Level 1 (Copanlisib, Abemaciclib, Fulvestrant)	Phase I Part A Dose Level 2 (Copanlisib, Abemaciclib, Fulvestrant)	Phase I Part B Dose Level 1b (Copanlisib, Abemaciclib, Fulvestrant)	Phase I Part B Dose Level 2b (Copanlisib, Abemaciclib, Fulvestrant)	Total
Hispanic or Latino	1	0	0	0	1
Not Hispanic or Latino	6	3	7	7	23
Unknown or Not Reported	0	0	0	0	0

Race (NIH/OMB)
Race (NIH/OMB)(Participants)	Phase I Part A Dose Level 1 (Copanlisib, Abemaciclib, Fulvestrant)	Phase I Part A Dose Level 2 (Copanlisib, Abemaciclib, Fulvestrant)	Phase I Part B Dose Level 1b (Copanlisib, Abemaciclib, Fulvestrant)	Phase I Part B Dose Level 2b (Copanlisib, Abemaciclib, Fulvestrant)	Total
American Indian or Alaska Native	0	0	0	0	0
Asian	0	0	2	1	3
Native Hawaiian or Other Pacific Islander	0	0	0	0	0
Black or African American	0	1	0	1	2
White	7	2	5	5	19
More than one race	0	0	0	0	0
Unknown or Not Reported	0	0	0	0	0

Region of Enrollment
Region of Enrollment(participants)	Phase I Part A Dose Level 1 (Copanlisib, Abemaciclib, Fulvestrant)	Phase I Part A Dose Level 2 (Copanlisib, Abemaciclib, Fulvestrant)	Phase I Part B Dose Level 1b (Copanlisib, Abemaciclib, Fulvestrant)	Phase I Part B Dose Level 2b (Copanlisib, Abemaciclib, Fulvestrant)	Total
United States	7	3	7	7	24

Study locations

14 sites

University of Alabama at Birmingham Cancer Center
Birmingham, Alabama 35233, United States
UC Irvine Health Cancer Center-Newport
Costa Mesa, California 92627, United States
UC Irvine Health/Chao Family Comprehensive Cancer Center
Orange, California 92868, United States
University of Kentucky/Markey Cancer Center
Lexington, Kentucky 40536, United States
Siteman Cancer Center at Saint Peters Hospital
City of Saint Peters, Missouri 63376, United States
Siteman Cancer Center at West County Hospital
Creve Coeur, Missouri 63141, United States
Washington University School of Medicine
St Louis, Missouri 63110, United States
Siteman Cancer Center-South County
St Louis, Missouri 63129, United States
Siteman Cancer Center at Christian Hospital
St Louis, Missouri 63136, United States
Bellevue Hospital Center
New York, New York 10016, United States
Laura and Isaac Perlmutter Cancer Center at NYU Langone
New York, New York 10016, United States
Wake Forest University at Clemmons
Clemmons, North Carolina 27012, United States
Wake Forest University Health Sciences
Winston-Salem, North Carolina 27157, United States
Ohio State University Comprehensive Cancer Center
Columbus, Ohio 43210, United States

References and documents

Study documents

Protocol and statistical analysis plan · Jun 13, 2024
Informed consent form · Jun 13, 2024
Informed consent form · Jun 13, 2024

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: 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.

Updates

Tracking since Sep 25, 2026

No changes since tracking began. The registry record was last updated on Sep 8, 2026, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT03939897
Lead sponsor: National Cancer Institute (NCI)
Responsible party: Sponsor
First posted: May 7, 2019
Start date: Jun 17, 2020
Primary completion: Jun 22, 2023
Completion: Jul 31, 2027 (estimated)
Results posted: Jul 30, 2024
Last update: Sep 8, 2026

Study contacts

Cynthia X Ma

principal investigator · Yale University Cancer Center LAO

Oversight

Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No

View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is active, not recruiting, as verified in Sep 2026. You cannot join it, but the record below documents what was studied.

Follow this study

Get an email when the registry record changes — status, dates, results — or when someone posts here.

Discussion

Questions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.

Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.

Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.

Other studies in this condition

Breast Neoplasms→

Other studies from this sponsor

National Cancer Institute (NCI)

Start the discussion