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

• ClinicalTrials.gov Identifier: NCT05036005
• Recruitment Status: Recruiting
• First Posted: September 5, 2021
• Last Update Posted: September 5, 2021
• Sponsor: Institut fuer Frauengesundheit
• Collaborator: Samsung Bioepis Co., Ltd.
• Information provided by (Responsible Party): Institut fuer Frauengesundheit

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Breast Cancer; Breast Neoplasms; Breast Cancer Female; HER2-positive Breast Cancer	Drug: Ontruzant; Drug: Chemotherapy; Drug: Pertuzumab	Phase 4

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 108 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Neoadjuvant Treatment of Ontruzant (SB3) in Patients With HER2-positive Early Breast Cancer: An Open-Label, Multicenter, Phase IV Study
• Actual Study Start Date: July 11, 2021
• Estimated Primary Completion Date: January 2022
• Estimated Study Completion Date: January 2023

Arms and Interventions

Arm

Intervention/treatment

Experimental: 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.

Drug: 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.; Other Name: SB3; 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; 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.

Outcome Measures

Primary Outcome Measures :

1. Pathological complete response (pCR) rate [ Time Frame: Pathological complete response will be assessed at final surgery. ]
   Pathological complete response (pCR) rate, defined as the complete absence of tumor cells (ypT0; ypN0) after neoadjuvant study treatment of HER2-positive early breast cancer patients treated with Ontruzant® (SB3) in combination with pertuzumab (optional) and a standard chemotherapy.

Secondary Outcome Measures :

1. Pathological complete response (pCR) rate in patients without pertuzumab [ Time Frame: Pathological complete response will be assessed at final surgery. ]
   Pathological complete response (pCR) rate, defined as the complete absence of tumor cells (ypT0; ypN0) after neoadjuvant study treatment of HER2-positive early breast cancer patients treated with Ontruzant® (SB3) and a standard chemotherapy who were not treated with pertuzumab.
2. Number of participants wuth treatment-related adverse events as assessed by CTCAE v5.0 [ Time Frame: Adverse ebents will be assessed from first administration of trial treatment until 30 days after last administration of trial treatment. ]
   The safety endpoints for the study will include rate of AE/SAEs and fatal SAEs, causality and outcome of AE/SAEs, rate of treatment discontinuations and reasons, Changes in vital signs, laboratory values etc. Grading of AE/SAEs will be based on NCI CTCAE v5.0.
3. EORTC-QLQ-C30 [ Time Frame: Every nine weeks from first administration of trial medication through study completion, up to 30 days after administration of last medication. ]
   To evaluate changes in health related quality of life (QoL) assessments from baseline in all subjects using Quality of Life Questionnaire Core 30 (EORTC QLQ-C30).
4. EORTC-QLQ-BR23 [ Time Frame: Every nine weeks from first administration of trial medication through study completion, up to 30 days after administration of last medication. ]
   To evaluate changes in health related quality of life (QoL) assessments from baseline in all subjects using Quality of Life Questionnaire Breast Cancer-Specific Quality of Life (EORTC QLQ-BR23).

Other Outcome Measures:

1. To assess the antibody-dependent cell mediated cytotoxicity (ADCC) [ Time Frame: Measured from biomaterial collected at baseline, 12 weeks after treatment initiation and at surgery ]
   ADCC will be quantified and immune phenotyping will be performed from peripheral blood mononuclear cells (PBMCs).
2. FcγR genotypes [ Time Frame: Measured from biomaterial collected at baseline, 12 weeks after treatment initiation and at surgery ]
   Germline DNA will be genotyped in order to specify FcγR polymorphisms and impact of FcγR genotypes on ADCC and pCR will be assessed.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

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.
7. Multicentric and/or multifocal disease as well as synchronous bilateral breast cancer is eligible as long as one measurable lesion meets all inclusion criteria. The investigator has to determine which lesion will be used for tumor evaluation before initiation of treatment.
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.

Contacts and Locations

Contacts

Contact: NeoON Study Manager; +49 9131 9279136; neo.on@ifg-erlangen.de

Locations

Germany

Division Gynecologic Oncology, Heidelberg University Hospital (UKHD); Not yet recruiting

Heidelberg, Baden-Wuerttemberg, Germany, 69120

Contact: Andreas Schneeweiss, MD, Prof. +49 (0) 6221 563 6051 andreas.schneeweiss@med.uni-heidelberg.de

Department of Gynecology, Tübingen University Hospital; Not yet recruiting

Tübingen, Baden-Wuerttemberg, Germany, 72076

Contact: Andreas Hartkopf, MD, Prof. +49 70712982211 andreas.hartkopf@med.uni-tuebingen.de

Hämato-Onkologische Schwerpunktpraxis am Klinikum Aschaffenburg; Not yet recruiting

Aschaffenburg, Bavaria, Germany, 63739

Contact: Manfred Welslau, MD +49 6021 4527300 info@onkologie-ab.de

Department of Gynecology and Obstetrics, Erlangen University Hospital; Recruiting

Erlangen, Bavaria, Germany, 91054

Contact: Peter A Fasching, MD, Prof. +49 9131 8543470 peter.fasching@uk-erlangen.de

Department of Gynecology, University Hospital Hamburg-Eppendorf; Not yet recruiting

Hamburg, Haburg, Germany, 20246

Contact: Volkmar Müller, MD, Prof. +49 40 7410 - 52510 vmueller@uke.de

Center for Hematology and Oncology Bethanien; Not yet recruiting

Frankfurt, Hesse, Germany, 60389

Contact: Hans Tesch, MD, Prof. +49 69 451080 info@onkologie-bethanien.de

Department of Gynecology and Obstetrics, University Medicine Mainz; Not yet recruiting

Mainz, Hesse, Germany, 55131

Contact: Marcus Schmidt, MD, Prof. +49 6131 176884 marcus.schmidt@unimedizin-mainz.de

Department for Gynecology and Obstetrics, Marienhospital Bottrop gGmbH; Not yet recruiting

Bottrop, North Rhine-Westphalia, Germany, 46236

Contact: Hans-Christian Kolberg, MD +49 2041 1061601 hans-christian.kolberg@mhb-bottrop.de

Department of Gynecology and Obstetrics, Dresden University Hospital Carl-Gustav Carus; Not yet recruiting

Dresden, Saxony, Germany, 01307

Contact: Pauline Wimberger, MD, Prof. +49 351 4583420 pauline.wimberger@uniklinikum-dresden.de

Department for Hematology, Oncology and Tumor Immunology Charité Campus Benjamin Franklin; Not yet recruiting

Berlin, Germany, 122000

Contact: Diana Lüftner, MD, Prof. +49 30 450513524 diana.lueftner@charite.de

Department of Gynecology and Obstetrics, HELIOS Hospital Berlin Buch GmbH; Not yet recruiting

Berlin, Germany, 13125

Contact: Michael Untch, MD, Prof. +49 30 940153300 michael.untch@helios-gesundheit.de

Sponsors and Collaborators

Institut fuer Frauengesundheit

Samsung Bioepis Co., Ltd.

Investigators

• Study Chair: Diana Lüftner, MD, Prof.; Department for Hematology, Oncology and Tumor Immunology Charité Campus Benjamin Franklin, Berlin
• Study Chair: Andreas Schneeweiss, MD, Prof.; National Center for Tumor Diseases (NCT), Head of Division Head of Division Gynecologic Oncology, Heidelberg University Hospital (UKHD)

More Information

• Responsible Party: Institut fuer Frauengesundheit
• ClinicalTrials.gov Identifier: NCT05036005
• Other Study ID Numbers: IFG-08-2019
• First Posted: September 5, 2021
• Last Update Posted: September 5, 2021
• Last Verified: August 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Institut fuer Frauengesundheit:

Ontruzant; Trastuzumab; Pertuzumab; neoadjuvant chemotherapy

Additional relevant MeSH terms:

Breast Neoplasms; Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Pertuzumab; Antineoplastic Agents, Immunological; Antineoplastic Agents