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

NCT04042051 | Terminated Phase 1 DMC

• 1 other identifier: CTRIAL-IE 17-13
• Study Type: interventional
• Target: 2
• Locations: 2 countries
• Sites: 3

Brief 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. 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.

Conditions

HER2-positive Breast Cancer; Metastatic Breast Cancer; Locally Advanced Breast Cancer; Unresectable Breast Cancer

Keywords

HER2; HER2-positive; Metastatic; Breast; Cancer

Outcome Measures

Primary Outcomes (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.

  1.5 years

Secondary Outcomes (8)

• 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.

  1.5-2.5 years

• Overall Survival (OS).

  1.5-2.5 years

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

  1.5-2.5 years

• 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).

  1.5-2.5 years

• Confirmed tumour response rate as assessed by RECIST criteria version 1.1

  1.5-2.5 years

Study Arms (1)

Single Arm

OTHER

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 (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.

Drug: Copanlisib; Drug: Trastuzumab emtansine

Interventions

Copanlisib DRUG

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.

Also known as: BAY 80-6946

Single Arm

Trastuzumab emtansine DRUG

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

Also known as: Kadcyla

Single Arm

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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:
• i. Combined (oestrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, transdermal).
• ii. Progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable and implantable).
• iii. Intrauterine device (IUD). iv. Intrauterine hormone-releasing system (IUS). v. Bilateral tubal occlusion. vi. Successfully vasectomised partner. vii. Sexual abstinence.

You may not qualify if:

• 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.
• 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).

Sponsors & Collaborators

• Cancer Trials Ireland: lead

Study Sites (3)

Cancer Trials Ireland Investigative Site

Cork, Ireland

Location

Cancer Trials Ireland Investigative Site

Dublin, Ireland

Location

Cancer Trials Ireland Investigative Site

Seville, Spain

Location

MeSH Terms

Conditions

Breast Neoplasms; Neoplasm Metastasis; Neoplasms

Interventions

copanlisib; Ado-Trastuzumab Emtansine

Condition Hierarchy (Ancestors)

Neoplasms by Site; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Maytansine; Macrolides; Lactones; Organic Chemicals; Lactams, Macrocyclic; Macrocyclic Compounds; Polycyclic Compounds; Trastuzumab; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Cancer Trials Ireland Dublin 11, Ireland

  Cancer Trials Ireland

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 31, 2019
• First Posted: August 1, 2019
• Study Start: November 12, 2019
• Primary Completion: November 2, 2020
• Study Completion: November 2, 2020
• Last Updated: July 22, 2025

Record last verified: 2025-07

Locations

IE (2); ES (1)