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HER2-positive Breast CancerPhase 1PantheraNCT04042051

Copanlisib in Combination With T-DM1 in Pretreated Unresectable Locally Advanced or Metastatic HER2-positive Breast Cancer

A Phase 1 study testing Copanlisib and Trastuzumab emtansine in people with HER2-positive Breast Cancer and Metastatic Breast Cancer, run by Cancer Trials Ireland at 3 sites in 2 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

This study is a Phase 1b open label, single arm, adaptive multi-centre trial of copanlisib in combination with trastuzumab emtansine (T-DM1) in pretreated locally advanced or metastatic HER2-positive breast cancer. Read more about this study

Who is it for?
Ages 18 years and older, women only
What is being tested?
Copanlisib and Trastuzumab emtansine
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
2 participants
Where
3 sitesin 2 countries
Study dates
12 Nov 2019to 2 Nov 2020
Phase
Phase 1
Are there results?
None posted in the registry

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
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Written informed consent must be provided before any study-specific tests or procedures are performed.
  • Adult women ≥ 18 years of age.
  • Histologically confirmed HER2-positive breast cancer:
  • Documented HER2 overexpression by local laboratory defined as a score of 3+ by IHC or a ratio of ≥ 2.0 by ISH.
  • HER2-positive on diagnostic breast biopsy or surgical breast resection sample or metastatic disease site biopsy.
  • Patient with unresectable locally advanced or metastatic breast cancer who previously received trastuzumab and a taxane, separately or in combination.
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  • Patient has received prior therapy for locally advanced or metastatic disease, or developed disease recurrence during or within six months of completing adjuvant therapy.
  • At least one measurable lesion according to RECIST criteria (Version 1.1). Patients with bone only disease are eligible if lesion(s) can be accurately assessed by CT/MRI according to RECIST (Version 1.1).
  • ECOG performance status ≤ 2.
  • Life expectancy of at least 3 months.
  • Availability of fresh tissue and/or archival tumour tissue at screening.
  • Women of childbearing potential must agree to use a highly effective method of contraception when sexually active. This applies from signing of the informed consent form until at least 7 months after the last study drug administration. The investigator or a designated associate is required to advise the patient how to achieve an adequate birth control. Highly effective contraception is defined in the study as methods that achieve a failure rate of less than 1% per year when used consistently and correctly. Such methods include:
  • Combined (oestrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, transdermal).
  • Progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable and implantable).
  • Intrauterine device (IUD). iv. Intrauterine hormone-releasing system (IUS). v. Bilateral tubal occlusion. vi. Successfully vasectomised partner. vii. Sexual abstinence.
  • Postmenopausal women defined as follows:
  • Woman 60 years of age or older, OR
  • Woman younger than 60 years of age with spontaneous cessation of menses for at least 12 consecutive months prior to registration, OR
  • Prior bilateral oophorectomy, OR
  • Woman younger than 60 years of age who have had a prior hysterectomy (without bilateral oophorectomy) AND who have an FSH level in the postmenopausal range (or >34.4 IU/L if institutional range is not available).
  • Adequate baseline laboratory values collected no more than 14 days before starting study treatment:
  • Total bilirubin ≤ 1.5 x ULN (< 3 x ULN for patients with metastatic disease in the liver)
  • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3.0 x ULN (≤ 5 x ULN for patients with liver involvement by breast cancer).
  • Lipase ≤ 1.5 x ULN.
  • Glomerular filtration rate (GFR) ≥ 30 mL/min/1.73 m2 according to the Modification of Diet in Renal Disease (MDRD) abbreviated formula. If not on target, this evaluation may be repeated once after at least 24 hours either according to the MDRD abbreviated formula or by 24 hour sampling. If the later result is within acceptable range, it may be used to fulfil the inclusion criteria instead.
  • International normalized ratio (INR) and partial thromboplastin time (PTT) ≤ 1.5 x ULN. Patients who are therapeutically treated with an agent such as warfarin or heparin will be allowed to participate provided that no prior underlying coagulopathy disorder. Close monitoring of these patients (Day 15 of Cycle 1 and Day 1 of each cycle) will be performed until INR/PTT is stable based on a measurement that is pre-dose as defined by the local standard of care.
  • Platelet count ≥ 75 x 109/L. For patients with breast cancer bone marrow infiltration, platelet count ≥ 50 x 109/L.
  • Haemoglobin (Hb) ≥ 8 g/dL.
  • Fasting blood glucose ≤6.0 mmol/L if not diabetic or ≤8.9 mmol/L if diabetic.
  • Absolute neutrophil count (ANC) ≥ 1 x 109/L. For patients with malignant bone marrow infiltration, ANC count ≥ 0.75 x 109/L.
  • Left ventricular ejection fraction (LVEF), at or above the Institutions lower limit of normal, as determined by ECHO or MUGA.
  • Patients must have recovered from clinically significant side effects associated with prior radiotherapy and chemotherapy with the exception of fatigue or neuropathy.

Who cannot join

  • Known breast cancer involvement of the brain, unless adequately controlled based on the clinical judgement of the treating physician.
  • Congestive heart failure > New York Heart Association (NYHA) class II.
  • Unstable angina (angina symptoms at rest), new-onset angina (begun within the last 3 months). Myocardial infarction less than 6 months before registration.
  • Uncontrolled arterial hypertension despite optimal medical management (per investigator's opinion).
  • Uncontrolled Type I or II diabetes mellitus. Defined as HbA1c > 8.5% as determined during screening laboratory assessments.
  • 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 registration.
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  • Non-healing wound, ulcer, or bone fracture.
  • Active, clinically serious infections > Grade 2 (CTCAE v5.0).
  • Known history of human immunodeficiency virus (HIV) infection.
  • 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 laboratory panel Patients who test positive for Hepatitis B surface Antigen (HBsAg) or Hepatitis B core Antigen (HBcAb) will be eligible if they are negative for HBV-DNA; patients who test positive for anti-HCV antibody will be eligible if they are negative for HCV-RNA.
  • Patients with CMV PCR positive.
  • Patients with seizure disorder requiring medication.
  • Patients with evidence or history of bleeding diathesis. Any haemorrhage or bleeding event ≥ CTCAE Grade 3 within 4 weeks prior to the start of study treatment.
  • Proteinuria of Grade 3 or higher (CTCAE v5.0). Patient will be excluded if > 2+ on urinalysis (unless 24 hr collection shows 24 hour urinary protein < 3.5g/24hrs).
  • History or concurrent condition of interstitial lung disease of any severity, and/or severely impaired lung functions (as judged by the investigator).
  • Concurrent diagnosis of pheochromocytoma.
  • Pregnant or breast-feeding patients. Women of childbearing potential must have a serum or urine pregnancy test within 7 days of first dose, and a negative result must be documented before start of treatment.
  • Unresolved toxicity higher than CTCAE Grade 1 attributed to any prior therapy/procedure, excluding alopecia, peripheral neuropathy, and bone marrow parameters.
  • Known hypersensitivity to any of the test drugs, test drug classes, or excipients in the formulation.
  • Substance abuse, medical, psychological or social conditions that may interfere with the patient's participation in the study or evaluation of the study results.
  • Any illness or medical conditions that are unstable or could jeopardise the safety of patients and their compliance in the study.
  • Patients permanently withdrawn from study participation will not be allowed to re-enter the study.

Trial locations and contacts

3 sites in 2 countries.

3 sites in 2 countries

Ireland2 sites

  • Cancer Trials Ireland Investigative Site

    Cork

  • Cancer Trials Ireland Investigative Site

    Dublin

Other trials in Ireland

Spain1 site

  • Cancer Trials Ireland Investigative Site

    Seville

Other trials in Spain

About this study

Official title: Phase Ib Clinical Trial of Copanlisib in Combination With Trastuzumab Emtansine (T-DM1) in Pretreated Unresectable Locally Advanced or Metastatic HER2-positive Breast Cancer "Panthera"

This study is a Phase 1b open label, single arm, adaptive multi-centre trial of copanlisib in combination with trastuzumab emtansine (T-DM1) in pretreated locally advanced or metastatic HER2-positive breast cancer.

Patients with unresectable locally advanced or metastatic HER2-positive breast cancer who previously received trastuzumab and a taxane, separately or in combination, will be treated with copanlisib (to the dose escalation scheme) plus trastuzumab emtansine 3.6mg/kg IV on day 1 of a 21-day cycle.

Read the detailed description

This study is a phase Ib open label, single arm, adaptive multi-centre trial. Patients with unresectable locally advanced or metastatic HER2-positive breast cancer who previously received trastuzumab and a taxane, separately or in combination, will be treated with copanlisib plus trastuzumab emtansine 3.6mg/kg IV on day 1 of a 21-day cycle.

3 to 6 patients will be enrolled per dose level. All patients in each level must have completed at least the first cycle of therapy before enrolment in the next dose level begins. Patients not completing the first cycle for a reason other than toxicity will be replaced.

Copanlisib will start at a low level and dose escalations will be performed in cohorts of 3 patients according to a standard 3+3 algorithm.

Dose escalation and determination of maximum tolerated dose (MTD) will be based on occurrences of Dose Limiting Toxicities (DLT).

The first cohort of 3 patients will commence at dose level 1. All patients in each cohort will be observed for one cycle on the specified dose:

  • If none of 3 patients at a given dose level experiences a DLT, accrual will continue to the next dose level according to the protocol.
  • If 1 of 3 patients experiences a DLT at a given dose level, 3 additional patients will be treated at the same dose. If no additional patient has a DLT in this cohort, accrual will continue to the next dose level according to the protocol.
  • If 2 or more patients in 3 or 6 patients treated at a given dose experience a DLT, the dose will be de-escalated to the next lower dose level, which will define the MTD.

If 2 or more patients in 3 or 6 patients treated at the -1 dose level experience DLT, the trial will be stopped.

Primary Objective:

  1. To determine the Maximum Tolerated Dose (MTD), for copanlisib in combination with trastuzumab emtansine (T-DM1) in patients with pretreated unresectable locally advanced or metastatic HER2-positive breast cancer.

Secondary Objectives:

  1. To evaluate the safety and tolerability of this regimen.
  2. To evaluate efficacy measures in patients treated with this regimen.
  3. To assess the incidence of cardiotoxicity in patients treated with this regimen.

Exploratory Objectives:

  1. To examine for predictive biomarkers in tumour tissue and blood.
  2. To examine molecular tumour adaptation to clinical trial therapy.
Being tested
Copanlisib, Trastuzumab emtansine
Keywords
HER2, HER2-positive, Metastatic, Breast, Cancer
Medical subject headings
Breast Neoplasms, Neoplasm Metastasis, Neoplasms

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 is supplied as lyophilized preparation in a 6mL injection vial. The total amount of copanlisib per vial is 60mg. The solution for IV infusions is obtained after reconstitution with normal saline solution. Copanlisib will be administered on Days 1 (and 8 and 15 [according to the dose escalation scheme]) of each 21-day cycle. Copanlisib will be administered first over 60 minutes followed by the infusion of trastuzumab emtansine.

  • Trastuzumab emtansineDrug

    Also called Kadcyla

    Trastuzumab emtansine 3.6mg/kg IV infusion on Day 1 of each 21-day treatment cycle.

Study groups in NCT04042051
Study groupRoleWhat they receive
Single ArmOtherThis study is a phase Ib open label, single arm, adaptive multi-centre trial. Patients with unresectable locally advanced or metastatic HER2-positive breast cancer who previously received trastuzumab and a taxane, separately or in combination, will be treated with copanlisib (as assigned at registration according to the dose escalation scheme) plus trastuzumab emtansine 3.6mg/kg IV on day 1 of a 21-day cycle.
Receives: Drug: Copanlisib; Drug: Trastuzumab emtansine

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. To determine the incidence of dose limiting toxicity (DLT) of copanlisib in combination with trastuzumab emtansine within the 1st cycle at each dose level.

    Measured: 1.5 years

Secondary outcomes (8)

  1. Clinical Benefit Rate (CBR) is defined as complete response (CR) or partial response (PR) at any time-point on the study; or stable disease (SD) lasting at least 24 weeks based on radiological assessment.

    Measured: 1.5-2.5 years

  2. Overall Survival (OS).

    Measured: 1.5-2.5 years

  3. Progression-Free Survival (PFS) assessed according to RECIST criteria version 1.1.

    Measured: 1.5-2.5 years

  4. Time to Treatment Failure (TTF) is defined as time from registration to discontinuation of therapy or add-on of new anti-cancer therapy for any reason (including death, progression and toxicity).

    Measured: 1.5-2.5 years

  5. Confirmed tumour response rate as assessed by RECIST criteria version 1.1

    Measured: 1.5-2.5 years

  6. Duration of response (DR) as assessed by standard RECIST criteria version 1.1.

    Measured: 1.5-2.5 years

  7. To evaluate the safety and tolerability of this regimen as measured by incidence of adverse events reported and toxicity evaluation as per the NCI Common Terminology Criteria for Adverse Events (CTCAE version 5.0).

    Measured: 1.5-2.5 years

  8. To assess the incidence of cardiotoxicity in patients treated with this regimen.

    Measured: 1.5-2.5 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted1 Aug 2019
  2. Study start12 Nov 2019
  3. Primary completion2 Nov 2020
  4. Study completion2 Nov 2020

Why it stopped: Accrual rate to date was too low to finish the trial in a reasonable timeframe

Resources

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
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
2 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04042051
Sponsor's protocol ID
CTRIAL-IE 17-13
Acronym
Panthera
Status last verified
Jul 2025
First submitted
31 Jul 2019
Last updated
22 Jul 2025
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Undecided

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Copanlisib and Trastuzumab emtansine in people with HER2-positive Breast Cancer and Metastatic Breast Cancer, run by Cancer Trials Ireland at 3 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 32 inclusion and 22 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: stopped early, as of the sponsor's last update on 22 Jul 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in Ireland, Spain. 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 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.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: Accrual rate to date was too low to finish the trial in a reasonable timeframe). Results are not available in the source record.

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?

To determine the incidence of dose limiting toxicity (DLT) of copanlisib in combination with trastuzumab emtansine within the 1st cycle at each dose level. (time frame: 1.5 years). 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 NCT04042051.

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 22 Jul 2025.

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