Neoadjuvant Ontruzant (SB3) in Patients With HER2-positive Early Breast Cancer: An Open-Label (NeoON)

NCT ID: NCT05036005

Last Updated: 2023-04-18

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE4
• Total Enrollment: 108 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-07-11
• Study Completion Date: 2023-07-31

Brief Summary

The treatment of patients with HER2 positive early breast cancer has continuously improved over the last decades. Up to now both, trastuzumab and pertuzumab are approved in combination with chemotherapy (CTX) not only for the adjuvant but also for the neoadjuvant treatment of early breast cancer patients. A high pCR rate in the neoadjuvant setting was shown in several trials and observational studies with CTX+ trastuzumab and with CTX+ pertuzumab. The efficacy is dependent on a variety of mechanisms including the blocking of the important PI3K/Akt and MAPK pathways, and ADCC (antibody dependent cellular toxicity).

Recently the biosimilar Ontruzant® (SB3) has been introduced into the treatment of HER2 positive breast cancer as a biosimilar. Efficacy and toxicity have been shown to be equivalent to the first approved antibody, however, data from the real-world setting have not been published like it has for the originally approved antibody. Therefore, the aim of this study is to establish safety and efficacy for Ontruzant® in the real world setting. Patients can be included if they are treated with Ontruzant® in the neoadjuvant setting. Additionally, the study will be accompanied by a comprehensive immune monitoring program and biomarker program to explore immune oncology potential for the neoadjuvant treatment.

Conditions

Breast Cancer; Breast Neoplasms; Breast Cancer Female; HER2-positive Breast Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Ontruzant + Pertuzumab (optional) + Chemotherapy

All patients will receive 6 cycles of Ontruzant® i.v. q21d in combination with standard chemotherapy with or without pertuzumab, at the discretion of investigator's decision. Initial dose of Ontruzant® i.v. will be 8 mg/kg b.w. followed by 5 cycles of Ontruzant® i.v. 6 mg/kg b.w. q21d. Clinical and bioptic tumor assessment will be performed during baseline and during surgery.

Study treatment will be applied until state of the art surgery, onset of unacceptable toxicities, progression or withdrawal of consent. A safety follow-up is planned for 30 days after the last administration of study medication.

Group Type: EXPERIMENTAL

Ontruzant

Intervention Type: DRUG

All patients will receive an initial dose of Ontruzant® i.v. 8 mg/kg b.w in combination with standard chemotherapy with or without pertuzumab i.v. 480 mg followed by 5 cycles of Ontruzant® i.v. 6 mg/kg b.w. q21d in combination with standard chemotherapy with or without pertuzumab i.v. 420 mg. Addition of pertuzumab is at the discretion of investigator's decision.

Chemotherapy

Intervention Type: DRUG

All patients will receive an initial dose of Ontruzant® i.v. 8 mg/kg b.w in combination with standard chemotherapy with or without pertuzumab i.v. 480 mg followed by 5 cycles of Ontruzant® i.v. 6 mg/kg b.w. q21d in combination with standard chemotherapy with or without pertuzumab i.v. 420 mg. Choice of chemotherapy is at the discretion of the investigator

Pertuzumab

Intervention Type: DRUG

All patients will receive an initial dose of Ontruzant® i.v. 8 mg/kg b.w in combination with standard chemotherapy with or without pertuzumab i.v. 480 mg followed by 5 cycles of Ontruzant® i.v. 6 mg/kg b.w. q21d in combination with standard chemotherapy with or without pertuzumab i.v. 420 mg. Addition of pertuzumab is at the discretion of investigator's decision.

Interventions

Ontruzant

All patients will receive an initial dose of Ontruzant® i.v. 8 mg/kg b.w in combination with standard chemotherapy with or without pertuzumab i.v. 480 mg followed by 5 cycles of Ontruzant® i.v. 6 mg/kg b.w. q21d in combination with standard chemotherapy with or without pertuzumab i.v. 420 mg. Addition of pertuzumab is at the discretion of investigator's decision.

Intervention Type: DRUG

Chemotherapy

All patients will receive an initial dose of Ontruzant® i.v. 8 mg/kg b.w in combination with standard chemotherapy with or without pertuzumab i.v. 480 mg followed by 5 cycles of Ontruzant® i.v. 6 mg/kg b.w. q21d in combination with standard chemotherapy with or without pertuzumab i.v. 420 mg. Choice of chemotherapy is at the discretion of the investigator

Intervention Type: DRUG

Pertuzumab

All patients will receive an initial dose of Ontruzant® i.v. 8 mg/kg b.w in combination with standard chemotherapy with or without pertuzumab i.v. 480 mg followed by 5 cycles of Ontruzant® i.v. 6 mg/kg b.w. q21d in combination with standard chemotherapy with or without pertuzumab i.v. 420 mg. Addition of pertuzumab is at the discretion of investigator's decision.

Intervention Type: DRUG

Other Intervention Names

SB3

Eligibility Criteria

Inclusion Criteria

1. Written informed consent prior to beginning of trial specific procedures.

2. Subject must be female and aged ≥ 18 years on day of signing informed consent.

3. ECOG 0-1.

4. Histologically confirmed, early HER2 positive breast cancer determined by core biopsy of breast tumor lesion.

5. Measurable tumor lesion with a size of ≥ 1 cm assessed by sonography or magnetic resonance imaging (MRI) within ≤ 28 days prior to entry. In case of inflammatory disease, the extent of inflammation will be measured.

6. Indication for chemotherapy.

8. Complete staging within 8 weeks prior to entry with no evidence of distant disease, including bilateral mammography, breast ultrasound, chest-X-ray (or chest CT-scan), liver ultrasound (or liver CT-scan or liver MRI) and bone scan.

9. Subjects must provide a core biopsy from tumor lesion before first chemotherapy, after 3 cycles of chemotherapy and after last neoadjuvant study treatment for biomarker analyses.

10. Adequate organ function defined as: Absolute neutrophile count ≥1500/µL, Platelets ≥100 000/µL, Hemoglobin ≥10.0 g/dL or ≥6.2 mmol/L, Creatinine ≤1.5 × ULN OR measured or calculated creatinine clearance ≥30 mL/min for participant with creatinine levels >1.5 × institutional ULN (GFR can also be used in place of creatinine or CrCl), Total bilirubin ≤1.5 ×ULN OR direct bilirubin ≤ULN for participants with total bilirubin levels >1.5 × ULN, AST (SGOT) and ALT (SGPT) ≤2.5 × ULN (≤5 × ULN for participants with liver metastases), International normalized ratio (INR) OR prothrombin time (PT) ≤1.5 × ULN unless participant is receiving anticoagulant therapy as long as PT or aPTT is within therapeutic range of intended use of anticoagulants, LVEF > 50 %

11. Female subjects of childbearing potential must have a negative urine pregnancy test within 72 h prior to study entry and be willing to use an adequate method of contraception for course of the study through 7 months after the last dose of trial treatment.

Exclusion Criteria

1. Concurrent participation in a study with an investigational agent/device or within 14 days of study entry.

2. Prior chemotherapy, radiation therapy or small molecule therapy for any reason.

3. Previous malignant disease being disease-free for less than 3 years (except in situ carcinoma of the cervix and basal cell carcinoma of the skin).

4. Pregnancy or lactation.

5. Prior neoadjuvant therapy.

6. Active infection requiring systemic therapy.

7. History of (non-infectious) pneumonitis that required steroids or current pneumonitis.

8. Active autoimmune disease or other diseases that requires systemic treatment with corticosteroids or immunosuppressive drugs (physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency is allowed).

9. History of primary or acquired immunodeficiency (including allogenic organ transplant).

10. Active or prior documented inflammatory bowel disease (e.g., Crohn's disease, ulcerative colitis).

11. Known history of following infections: Human immunodeficiency virus (HIV), History of acute or chronic Hepatitis B or Hepatitis C, has received a live-virus vaccination within 30 days of planned treatment start. Seasonal flu vaccines that do not contain live virus are permitted.

12. Known congestive heart failure > NYHA I and/or coronary heart disease, angina pectoris, previous history of myocardial infarction, uncontrolled or poorly controlled arterial hypertension (e.g. blood pressure >160/90 mmHg under treatment with two or more antihypertensive drugs), rhythm disorders with clinically significant valvular heart disease.

13. Pre-existing motor or sensory neuropathy of a severity grade ≥2 by National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) v5.0.

14. Any other condition in opinion of the investigator that would interfere with applied systemic treatment or other trial procedures.

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Samsung Bioepis Co., Ltd.

INDUSTRY

Sponsor Role: collaborator

Institut fuer Frauengesundheit

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Diana Lüftner, MD, Prof.

Role: STUDY_CHAIR

Department for Hematology, Oncology and Tumor Immunology Charité Campus Benjamin Franklin, Berlin

Andreas Schneeweiss, MD, Prof.

Role: STUDY_CHAIR

National Center for Tumor Diseases (NCT), Head of Division Head of Division Gynecologic Oncology, Heidelberg University Hospital (UKHD)

Locations

Division Gynecologic Oncology, Heidelberg University Hospital (UKHD)

Heidelberg, Baden-Wurttemberg, Germany

Site Status: RECRUITING

Department of Gynecology, Tübingen University Hospital

Tübingen, Baden-Wurttemberg, Germany

Site Status: NOT_YET_RECRUITING

Hämato-Onkologische Schwerpunktpraxis am Klinikum Aschaffenburg

Aschaffenburg, Bavaria, Germany

Site Status: RECRUITING

Department of Gynecology and Obstetrics, Erlangen University Hospital

Erlangen, Bavaria, Germany

Site Status: RECRUITING

Department of Gynecology, University Hospital Hamburg-Eppendorf

Hamburg, Haburg, Germany

Site Status: NOT_YET_RECRUITING

Center for Hematology and Oncology Bethanien

Frankfurt am Main, Hesse, Germany

Site Status: NOT_YET_RECRUITING

Department of Gynecology and Obstetrics, University Medicine Mainz

Mainz, Hesse, Germany

Site Status: NOT_YET_RECRUITING

Department for Gynecology and Obstetrics, Marienhospital Bottrop gGmbH

Bottrop, North Rhine-Westphalia, Germany

Site Status: RECRUITING

Department of Gynecology and Obstetrics, Dresden University Hospital Carl-Gustav Carus

Dresden, Saxony, Germany

Site Status: NOT_YET_RECRUITING

Department for Hematology, Oncology and Tumor Immunology Charité Campus Benjamin Franklin

Berlin, , Germany

Site Status: NOT_YET_RECRUITING

Department of Gynecology and Obstetrics, HELIOS Hospital Berlin Buch GmbH

Berlin, , Germany

Site Status: NOT_YET_RECRUITING

Countries

Germany

Central Contacts

NeoON Study Manager

Role: CONTACT

neo.on@ifg-erlangen.de

+49 9131 9279136

Facility Contacts

Andreas Schneeweiss, MD, Prof.

Role: primary

andreas.schneeweiss@med.uni-heidelberg.de

+49 (0) 6221 563 6051

Andreas Hartkopf, MD, Prof.

Role: primary

andreas.hartkopf@med.uni-tuebingen.de

+49 70712982211

Manfred Welslau, MD

Role: primary

info@onkologie-ab.de

+49 6021 4527300

Peter A Fasching, MD, Prof.

Role: primary

peter.fasching@uk-erlangen.de

+49 9131 8543470

Volkmar Müller, MD, Prof.

Role: primary

vmueller@uke.de

+49 40 7410 - 52510

Hans Tesch, MD, Prof.

Role: primary

info@onkologie-bethanien.de

+49 69 451080

Marcus Schmidt, MD, Prof.

Role: primary

marcus.schmidt@unimedizin-mainz.de

+49 6131 176884

Hans-Christian Kolberg, MD

Role: primary

hans-christian.kolberg@mhb-bottrop.de

+49 2041 1061601

Pauline Wimberger, MD, Prof.

Role: primary

pauline.wimberger@uniklinikum-dresden.de

+49 351 4583420

Diana Lüftner, MD, Prof.

Role: primary

diana.lueftner@charite.de

+49 30 450513524

Michael Untch, MD, Prof.

Role: primary

michael.untch@helios-gesundheit.de

+49 30 940153300

Other Identifiers

IFG-08-2019

Identifier Type: -

Identifier Source: org_study_id