Efficacy and Safety Study of ABP 980 Compared With Trastuzumab in Women With HER2-positive Early Breast Cancer

NCT01901146 | Completed Phase 3 Results DMC

• 2 other identifiers: 201202832012-004319-29
• Study Type: interventional
• Target: 725
• Locations: 18 countries
• Sites: 98

Brief Summary

The purpose of this research study is to compare the effectiveness and safety of ABP 980 against trastuzumab in women with human epidermal growth factor receptor 2 (HER2)-positive early breast cancer.

Conditions

Breast Cancer

Keywords

Human Epidermal Growth Factor Receptor 2 (HER2); Positive Early Breast Cancer

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants With a Pathologic Complete Response

  Pathologic complete response (pCR) was defined as the absence of invasive tumor cells in the breast tissue and in axillary lymph nodes, regardless of residual ductal carcinoma in situ (DCIS). Participants underwent a lumpectomy or mastectomy with sentinel lymph node dissection (SLND) or axillary lymph node dissection (ALND) within 3 to 7 weeks after the last dose of study drug in the neoadjuvant phase. The pathology evaluation of surgical specimens for pCR analysis was conducted by local laboratories at the study sites.

  3 to 7 weeks after the last dose of study drug in the neoadjuvant phase

Secondary Outcomes (2)

• Percentage of Participants With a Pathologic Complete Response in Breast Tissue Only

  3 to 7 weeks after the last dose of study drug in the neoadjuvant phase

• Percentage of Participants With a Pathologic Complete Response in Breast Tissue and Axillary Lymph Nodes and Absence of DCIS

  3 to 7 weeks after the last dose of study drug in the neoadjuvant phase

Study Arms (2)

ABP 980

EXPERIMENTAL

Participants received ABP 980 at an initial dose of 8 mg/kg by intravenous (IV) infusion, then 6 mg/kg IV infusion every 3 weeks (Q3W) for 3 additional cycles plus 175 mg/m² paclitaxel Q3W for 4 cycles during the neoadjuvant phase. Surgery (lumpectomy or mastectomy with sentinel lymph node dissection or axillary lymph node dissection) was completed 3 to 7 weeks after the last dose of study drug in the neoadjuvant phase. After surgery (adjuvant phase) participants continued receiving 6 mg/kg ABP 980 IV Q3W for up to 1 year from the first day of study drug administration in the neoadjuvant phase.

Drug: ABP 980; Drug: Paclitaxel; Procedure: Lumpectomy or Mastectomy with Sentinel Node or Axillary Node Dissection

Trastuzumab

ACTIVE COMPARATOR

Participants received trastuzumab at an initial dose of 8 mg/kg IV infusion, then 6 mg/kg IV infusion Q3W for 3 additional cycles plus 175 mg/m² paclitaxel Q3W for 4 cycles during the neoadjuvant phase. Surgery (lumpectomy or mastectomy with sentinel lymph node dissection or axillary lymph node dissection) was completed 3 to 7 weeks after the last dose of study drug in the neoadjuvant phase. After surgery (adjuvant phase) participants were re-randomized to either continue receiving 6 mg/kg trastuzumab IV Q3W or transition to 6 mg/kg ABP 980 IV Q3W for up to 1 year from the first day of study drug administration in the neoadjuvant phase.

Drug: Trastuzumab; Drug: Paclitaxel; Procedure: Lumpectomy or Mastectomy with Sentinel Node or Axillary Node Dissection

Interventions

ABP 980 DRUG

ABP 980 was administered at an initial dose of 8 mg/kg over a 90-minute intravenous (IV) infusion, then 6 mg/kg IV infusion Q3W for all subsequent cycles.

ABP 980

Trastuzumab DRUG

Trastuzumab was administered at an initial dose of 8 mg/kg over a 90-minute IV infusion, then 6 mg/kg IV infusion Q3W for all subsequent cycles.

Also known as: Herceptin®

Trastuzumab

Paclitaxel DRUG

Paclitaxel, 175 mg/m² Q3W for 4 cycles (or 80 mg/m² QW for 12 cycles, if local standard of care).

ABP 980; Trastuzumab

Lumpectomy or Mastectomy with Sentinel Node or Axillary Node Dissection PROCEDURE

ABP 980; Trastuzumab

Eligibility Criteria

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

You may qualify if:

• Females ≥ 18 years of age
• Histologically confirmed invasive breast cancer
• Planning for surgical resection of breast tumor and sentinel node or axillary lymph node resection
• Planning neoadjuvant chemotherapy
• HER2 positive disease
• Measurable disease in the breast after diagnostic biopsy, defined as longest diameter ≥ 2.0 cm
• Known estrogen receptor (ER) and progesterone receptor (PR) hormone receptor status at study entry
• Normal bone marrow function
• Normal hepatic function
• Normal renal function
• Subjects must sign an Institutional Review Board/Ethics Committee (IRB/EC)-approved informed consent form before any study specific procedures
• Left ventricular ejection fraction (LVEF) of ≥55% by 2D echocardiogram
• Complete all 4 cycles of run-in chemotherapy

You may not qualify if:

• Bilateral breast cancer
• Presence of known metastases
• Received prior treatment, including chemotherapy, biologic therapy, radiation or surgery with the exception of diagnostic biopsy for primary breast cancer
• Other concomitant active malignancy or history of malignancy in the past 5 years except treated basal cell carcinoma of the skin or carcinoma in situ of the cervix
• Pre-existing clinically significant (≥ grade 2) peripheral neuropathy
• Any history of documented or current congestive heart failure, current high-risk uncontrolled arrhythmias, current angina pectoris requiring a medicinal product, current clinically significant valvular disease, current evidence of transmural infarction on electrocardiogram (ECG), or current poorly controlled hypertension
• Severe dyspnea at rest requiring supplementary oxygen therapy
• History of positivity for hepatitis B surface antigen, hepatitis C virus, or human immunodeficiency virus (HIV)
• Recent infection requiring a course of systemic anti-infectives that were completed ≤ 14 days before enrollment (with the exception of uncomplicated urinary tract infection)
• Woman of childbearing potential who is pregnant or is breast feeding
• Woman of childbearing potential who is not consenting to use highly effective methods of birth control (eg, true abstinence \[periodic abstinence (eg calendar ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception\], sterilization, or other non-hormonal forms of contraception) during treatment and for at least 7 months after the last administration of the protocol specified treatment
• Currently receiving treatment in another investigational device or drug study, or less than 30 days since ending treatment on another investigational device or drug study
• Other investigational procedures while participating in this study are excluded
• Subject has known sensitivity to any of the products to be administered during the study, including mammalian cell derived drug products, trastuzumab, murine proteins, or to any of the excipients
• Subject previously has enrolled and/or has been randomized in this study

Sponsors & Collaborators

• Amgen: lead
• Actavis Inc.: collaborator

Study Sites (98)

Research Site

Brest, 224027, Belarus

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Grodno, 230017, Belarus

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Minsk, 220013, Belarus

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Minsk, 223040, Belarus

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Salvador, Estado de Bahia, 41820-021, Brazil

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Ijuí, Rio Grande do Sul, 98700-000, Brazil

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Porto Alegre, Rio Grande do Sul, 91350-200, Brazil

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Jaú, São Paulo, 17210-080, Brazil

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Santo André, São Paulo, 09060-650, Brazil

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São Paulo, São Paulo, 04039-004, Brazil

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Sofia, Sofia, 1756, Bulgaria

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Veliko Tarnovo, Veliko Tarnovo, 5000, Bulgaria

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Pleven, 5800, Bulgaria

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Varna, 9010, Bulgaria

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Moncton, New Brunswick, E1C6Z8, Canada

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Montreal, Quebec, H1T 2M4, Canada

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Temuco, Cautín, 4810469, Chile

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Santiago, 8360160, Chile

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Fürstenwalde, Brandenburg, 15517, Germany

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Frankfurt am Main, Hesse, 60389, Germany

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Frankfurt am Main, Hesse, 60590, Germany

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Bonn, North Rhine-Westphalia, 53111, Germany

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Bottrop, North Rhine-Westphalia, 46236, Germany

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Berlin, 13353, Germany

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Athens, Attica, 11527, Greece

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Athens, Attica, 12462, Greece

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Heraklion, Crete, 71110, Greece

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Thessaloniki, Nea Efkarpia, 56429, Greece

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Debrecen, Hajdú-Bihar, 4032, Hungary

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Szolnok, Jász-Nagykun-Szolnok, 5000, Hungary

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Nyíregyháza, Szabolcs-Szatmár-Bereg, 4400, Hungary

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Szekszárd, Tolna County, 7100, Hungary

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Budapest, 1083, Hungary

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Budapest, 1122, Hungary

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San Fermo della Battaglia, COMO, 22040, Italy

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Bari, 74124, Italy

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Milan, 20141, Italy

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Palermo, 90127, Italy

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Parma, 43100, Italy

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Piacenza, 29100, Italy

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Varese, 21100, Italy

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Toluca, Estado de Mexico, Mexico, 50180, Mexico

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Monterrey, Nuevo León, 64710, Mexico

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San Luis Potosí City, San Luis Potosí, 78200, Mexico

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Querétaro, 76090, Mexico

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Poznan, Greater Poland Voivodeship, 60-569, Poland

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Poznan, Greater Poland Voivodeship, 61-485, Poland

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Bydgoszcz, Kuyavian-Pomeranian Voivodeship, 85-792, Poland

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Warszawa, Lublin Voivodeship, 20-090, Poland

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Warsaw, Masovian Voivodeship, 02-776, Poland

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Warsaw, Masovian Voivodeship, 03-291, Poland

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Gdansk, Pomeranian Voivodeship, 80-219, Poland

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Rybnik, Silesian Voivodeship, 44-217, Poland

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Cluj-Napoca, Cluj, 400006, Romania

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Ploieşti, Prahova, 100337, Romania

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Timișoara, Timiș County, 300595, Romania

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Brasov, 500091, Romania

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Cluj-Napoca, 400058, Romania

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Obninsk, Kaluzhskaya, 249036, Russia

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Moscow Region, Moscow, 143423, Russia

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Arkhangelsk, Primorskiy (Maritime) Kray, 163045, Russia

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Saransk, Respublika Mordoviya, 430032, Russia

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Yaroslavl, Yaroslavlr, 150054, Russia

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Chelaybinsk, 454087, Russia

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Moscow, 115478, Russia

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Nizhny Novgorod, 603081, Russia

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Pyatigorsk, 357502, Russia

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Ryazan, 390011, Russia

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Saint Petersburg, 195271, Russia

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Saint Petersburg, 197089, Russia

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Saint Petersburg, 197758, Russia

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Sochi, 354057, Russia

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Belgrade, 11000, Serbia

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Belgrade, 11080, Serbia

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Kamenitz, 21204, Serbia

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Kragujevac, 34000, Serbia

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Niš, 18000, Serbia

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Johannesburg, Gauteng, 2193, South Africa

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Durban, KwaZulu-Natal, 4091, South Africa

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Cape Town, Western Cape, 7405, South Africa

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Cape Town, Western Cape, 7700, South Africa

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Sabadell, Barcelona, 08208, Spain

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A Coruña, LA Coruna, 15009, Spain

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Lleida, Lleida, 25198, Spain

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Alcorcón, Madrid, 28921, Spain

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Barcelona, 08041, Spain

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Madrid, 28050, Spain

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Madrid, 28220, Spain

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Kyiv, Kyiv City, 03115, Ukraine

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Lutsk, Volyn Oblast, 43018, Ukraine

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Uzhhorod, Zakarpattia Oblast, 88000, Ukraine

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Chernivtsi, 58013, Ukraine

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Dnipropetrovsk, 49055, Ukraine

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Kharkiv, 61070, Ukraine

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Lviv, 79031, Ukraine

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Zaporizhzhya, 69040, Ukraine

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Nottingham, England, NG5 1PB, United Kingdom

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Peterborough, England, PE3 9GZ, United Kingdom

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Related Publications (2)

• Kolberg HC, Colleoni M, Demetriou GS, Santi P, Tesch H, Fujiwara Y, Tomasevic Z, Hanes V. Cardiac Safety of the Trastuzumab Biosimilar ABP 980 in Women with HER2-Positive Early Breast Cancer in the Randomized, Double-Blind, Active-Controlled LILAC Study. Drug Saf. 2020 Mar;43(3):233-242. doi: 10.1007/s40264-019-00886-3.

  PMID: 31927716 DERIVED

• von Minckwitz G, Colleoni M, Kolberg HC, Morales S, Santi P, Tomasevic Z, Zhang N, Hanes V. Efficacy and safety of ABP 980 compared with reference trastuzumab in women with HER2-positive early breast cancer (LILAC study): a randomised, double-blind, phase 3 trial. Lancet Oncol. 2018 Jul;19(7):987-998. doi: 10.1016/S1470-2045(18)30241-9. Epub 2018 Jun 4.

  PMID: 29880292 DERIVED

Related Links

• AmgenTrials clinical trials website

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Trastuzumab; Paclitaxel; Mastectomy, Segmental; Mastectomy

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Surgical Procedures, Operative

Results Point of Contact

• Title: Study Director
• Organization: Amgen Inc.

866-572-6436

Study Officials

• MD

  Amgen

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 20, 2013
• First Posted: July 17, 2013
• Study Start: April 29, 2013
• Primary Completion: May 5, 2016
• Study Completion: January 27, 2017
• Last Updated: August 7, 2019
• Results First Posted: August 7, 2019

Record last verified: 2018-02

Locations

BE (4); GR (4); CA (2); DE (6); ES (7); UA (8); CL (2); IT (7); BR (6); RO (5); RU (14); ZA (4); BU (4); PL (8); GB (2); ME (4); SE (5); HU (6)