A Randomized, Double-blind, Phase 3 Study of Tucatinib or Placebo in Combination With Trastuzumab and Pertuzumab as Maintenance Therapy for Metastatic HER2+ Breast Cancer (HER2CLIMB-05)
A Randomized, Double-blind, Phase 3 Study of Tucatinib or Placebo in Combination With Trastuzumab and Pertuzumab as Maintenance Therapy for Metastatic HER2+ Breast Cancer (HER2CLIMB-05)
This study is being done to see if tucatinib works better than placebo when given with other drugs to treat participants with HER2-positive breast cancer. A placebo is a pill that looks the same as tucatinib but has no medicine in it. This study will also test what side effects happen when participants take this combination of drugs. A side effect is anything a drug does to the body besides treating your disease.
Participants will have cancer that has spread in the body near where it started (locally advanced) and cannot be removed (unresectable) or has spread through the body (metastatic).
In this study, all participants will get either tucatinib or placebo. Participants will be assigned randomly to a group. This is a blinded study, so patients and their doctors will not know which group a participant is in.
All participants will also get trastuzumab and pertuzumab. These are 2 drugs used to treat this type of cancer.
Control arm: Placebo given orally twice daily plus trastuzumab and pertuzumab every 21 days
Experimental arm: Tucatinib 300 mg given orally twice daily plus trastuzumab and pertuzumab every 21 days
Trastuzumab and pertuzumab will be administered as follows:
• Trastuzumab will be given intravenously (IV) at a dose of 6 mg/kg or subcutaneously (SC) at a fixed dose of 600 mg, once every 21 days.
AND
Inclusion Criteria:
Centrally confirmed HER2+ breast carcinoma according to the 2018 American Society of Clinical Oncologists (ASCO) College of American Pathologists (CAP) guidelines prior to randomization (defined as a 3+ score on immunohistochemistry (IHC) and/or 2+ IHC and concurrent positive by ISH).
Have unresectable locally advanced or metastatic disease.
Have received 4-8 cycles of pre-study induction therapy including only trastuzumab, pertuzumab, and taxane as first-line of therapy for the treatment of advanced breast cancer prior to study enrollment. Participants are eligible provided they are without evidence of disease progression following completion of induction therapy.
Known hormone receptor status (per local guidelines; may be hormone receptor positive [HR+] or negative [HR-])
Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
CNS Inclusion - Based on screening contrast-enhanced brain magnetic resonance imaging (MRI), participants may have any of the following:
No evidence of brain metastases
Untreated brain metastases which are asymptomatic not needing immediate local treatment and, if identified on prior brain imaging, without evidence of progression since starting first-line induction therapy with trastuzumab, pertuzumab, and taxane
Previously treated brain metastases which are asymptomatic
Exclusion Criteria:
Prior treatment with any tyrosine kinase inhibitor targeting HER2 and/or epidermal growth factor receptor (EGFR) including pyrotinib, lapatinib, tucatinib, neratinib, and afatinib (except neratinib if given in extended adjuvant setting and ≥ 12 months have elapsed since last neratinib dose prior to start of study drug)
Unable to undergo contrast-enhanced MRI of the brain
CNS Exclusion - Based on screening brain MRI and clinical assessment
Little Rock, Arkansas 72205, United States
La Jolla, California 92037, United States
Torrance, California 90502, United States
Altamonte Springs, Florida 32701, United States
Chicago, Illinois 60612, United States
Chicago, Illinois 60612, United States
Grand Island, Nebraska 68803, United States
Grand Island, Nebraska 68803, United States
Lakewood, New Jersey 08701, United States
Somerville, New Jersey 08876, United States
West Long Branch, New Jersey 07764, United States
Macquarie University, New South Wales 2109, Australia
Westmead, New South Wales 2145, Australia
Subiaco, Washington 6008, Australia
Sao Paulo/SP, Other 01.509-010, Brazil
Porto Alegre, Rio Grande do Sul CEP 90110-270, Brazil
Porto Alegre, Rio Grande do Sul CEP 90850-170, Brazil
Santo André, São Paulo 09060-650, Brazil
Santo André, São Paulo 09060-870, Brazil
Porto Alegre/RS, 90050-170, Brazil
São Paulo, 01246-000, Brazil
São Paulo, CEP: 01317-000, Brazil
Chicoutimi, Quebec G7H 5H6, Canada
Wuhan, Hubei 430030, China
Hangzhou, Zhejiang 310052, China
Praha 4 - Krc, Other 14059, Czechia
Praha 5 - Motol, 15006, Czechia
Praha 5 - Motol, 15006, Czechia
Rouen, Brittany Region 76038, France
Saint-Herblain, Loire-atlantique 44800, France
Montpellier, 34298 Cedex 5, France
Plérin, 22190, France
München, 81675, Germany
Würzburg, 97080, Germany
Athens, Attica 11528, Greece
Patra, Peloponnese 26504, Greece
Pireaus, 18537, Greece
Naples, Campania 80131, Italy
Torrette, The Marches 60126, Italy
Trento, Trentino-Alto Adige 38122, Italy
Trento, Trentino-Alto Adige 38122, Italy
Livorno, Tuscany 57124, Italy
Kashiwa-Shi, Chiba 277-8577, Japan
Osakasayama-shi, Osaka 589-8511, Japan
Chuo-ku, Tokyo 104-0045, Japan
Chuo-ku, Tokyo 104-8560, Japan
Minato-ku, Tokyo 105-8470, Japan
Shinagawa-ku, Tokyo 142-8666, Japan
Doedrecht, South Holland 3318AT, Netherlands
Lodz, Other 93-513, Poland
Gliwice, Silesian Voivodeship 44-102, Poland
Coimbra, 3000-075, Portugal
Seoul, Seoul-teukbyeolsi [seoul] 03722, South Korea
EI Palmar, Murcia 30120, Spain
La Laguna Tenerife, Santa CRUZ DE Tenerife 38320, Spain
Taipei, Other 10449, Taiwan
New Taipei City, 23561 (R.O.C), Taiwan
New Taipei City, 23561 (R.O.C.), Taiwan