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A Study of Tucatinib (MK-7119) in Combination With Trastuzumab and Capecitabine in Participants With Previously Treated Locally Advanced Unresectable or Metastatic Human Epidermal Growth Factor Receptor 2 Positive (HER2+) Breast Carcinoma (MK-7119-001)

NCT04721977

Description:

The goal of this study is to evaluate the efficacy and safety of tucatinib in combination with trastuzumab and capecitabine in participants with unresectable locally advanced or metastatic HER2+ breast cancer who have had prior treatment with taxane anti-cancer agent, trastuzumab, pertuzumab and trastuzumab emtansine (T-DM1). The primary hypothesis is that the confirmed objective response rate (cORR) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) as determined by independent central review (ICR) for the combination of tucatinib, trastuzumab and capecitabine, is greater than 20%.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Study of Tucatinib (MK-7119) in Combination With Trastuzumab and Capecitabine in Participants With Previously Treated Locally Advanced Unresectable or Metastatic Human Epidermal Growth Factor Receptor 2 Positive (HER2+) Breast Carcinoma (MK-7119-001)
  • Official Title: A Phase 2 Open-label, Single Arm Study of MK-7119 in Combination With Trastuzumab and Capecitabine in Participants With Previously Treated Locally Advanced Unresectable or Metastatic HER2+ Breast Carcinoma

Clinical Trial IDs

  • ORG STUDY ID: 7119-001
  • SECONDARY ID: MK-7119-001
  • SECONDARY ID: jRCT2051200152
  • NCT ID: NCT04721977

Conditions

  • Breast Cancer

Interventions

DrugSynonymsArms
TucatinibMK-7119, TukysaTucatinib + Trastuzumab + Capecitabine
TrastuzumabHerceptin, Herceptin HylectaTucatinib + Trastuzumab + Capecitabine
CapecitabineXelodaTucatinib + Trastuzumab + Capecitabine

Purpose

The goal of this study is to evaluate the efficacy and safety of tucatinib in combination with trastuzumab and capecitabine in participants with unresectable locally advanced or metastatic HER2+ breast cancer who have had prior treatment with taxane anti-cancer agent, trastuzumab, pertuzumab and trastuzumab emtansine (T-DM1). The primary hypothesis is that the confirmed objective response rate (cORR) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) as determined by independent central review (ICR) for the combination of tucatinib, trastuzumab and capecitabine, is greater than 20%.

Trial Arms

NameTypeDescriptionInterventions
Tucatinib + Trastuzumab + CapecitabineExperimentalParticipants will receive tucatinib plus trastuzumab plus capecitabine. Tucatinib 300 mg will be administered orally twice daily (BID). Trastuzumab 8 mg/kg loading dose followed by 6 mg/kg maintenance dose thereafter, will be administered intravenously (IV) on Day 1 of each 21-day cycle. Capecitabine 1000 mg/m^2 will be administered orally BID on Days 1-14 of each 21-day cycle. Tucatinib, trastuzumab and capecitabine treatment will continue until unacceptable toxicity, disease progression, death, withdrawal of consent or study closure.
  • Tucatinib
  • Trastuzumab
  • Capecitabine

Eligibility Criteria

        Inclusion Criteria:

          -  Has histologically confirmed HER2+ breast carcinoma

          -  Has received previous treatment with taxane anti-cancer agent, trastuzumab,
             pertuzumab, and T-DM1 with the exception of when the use of taxanes is contraindicated
             or judged not to be the best treatment at the investigator's discretion

          -  Has radiographically and/or histologically confirmed disease progression on last
             systemic anticancer treatment

          -  Has adequate organ function

          -  Female participant is not pregnant or breastfeeding and is not a woman of childbearing
             potential (WOCBP) or is a WOCBP and using contraception or abstinent from heterosexual
             intercourse during the intervention period and for at least 30 days after receiving
             the last dose of tucatinib, 80 days after receiving the last dose of trastuzumab, or
             180 days after receiving the last dose of capecitabine, whichever occurs last and
             agrees to not donate eggs during this period

          -  Male participants refrain from donating sperm and are either abstinent from
             heterosexual intercourse or agree to use contraception during the intervention period
             and for at least 7 days after receiving the last dose of tucatinib and 90 days after
             receiving the last dose of capecitabine, whichever occurs last

          -  Previously treated brain metastasis is stable or progressed, provided there is no
             clinical indication for immediate re-treatment

        Exclusion Criteria:

          -  Has been previously treated with lapatinib within 12 months of starting study
             treatment

          -  Has been previously treated with neratinib, afatinib, tucatinib or capecitabine

          -  Has a history of exposure to doxorubicin, epirubicin, mitoxantrone, idarubicin,
             liposomal doxorubicin

          -  Has had treatment with any systemic anti-cancer therapy including hormonal therapy,
             non-central nervous system (CNS) radiation or experimental agent ≤3 weeks before first
             dose of study treatment

          -  Has any toxicity related to prior cancer therapies that has not resolved with the
             exception of alopecia, congestive heart failure, anemia

          -  Has clinically significant cardiopulmonary disease

          -  Has known myocardial infarction or unstable angina within 6 months prior to the first
             dose of study treatment

          -  Has any uncontrolled viral, bacterial or fungal infection within 14 days prior to the
             first dose of study treatment

          -  Is positive for Hepatitis B, Hepatitis C or has known chronic liver disease

          -  Is known to be positive for human immunodeficiency virus (HIV)

          -  Has evidence within 2 years of the start of study treatment of another malignancy that
             required systemic treatment

          -  Has ongoing use of systemic corticosteroids for control of symptoms of brain
             metastases

          -  Has any brain lesion thought to require immediate local therapy

          -  Has known or suspected leptomeningeal disease (LMD)

          -  Has poorly controlled generalized or complex partial seizures or manifest neurologic
             progression due to brain metastases
      
Maximum Eligible Age:N/A
Minimum Eligible Age:20 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Confirmed Objective Response Rate (cORR) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1), as Determined by Independent Central Review (ICR)
Time Frame:Up to ~21 months
Safety Issue:
Description:cORR is defined as the percentage of participants who have a confirmed Complete Response (CR: disappearance of all target lesions) or a Partial Response (PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters) per RECIST v1.1. The percentage of participants who experience a confirmed CR or PR as determined by ICR based on RECIST v1.1 will be presented.

Secondary Outcome Measures

Measure:cORR per RECIST v1.1, as Determined by Investigator Assessment (INV)
Time Frame:Up to ~92 months
Safety Issue:
Description:cORR is defined as the percentage of participants who have a confirmed CR (disappearance of all target lesions) or a PR (at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters) per RECIST v1.1. The percentage of participants who experience a confirmed CR or PR as determined by INV based on RECIST v1.1 will be presented.
Measure:Duration of Response (DOR) per RECIST v1.1, as Determined by ICR
Time Frame:Up to ~92 months
Safety Issue:
Description:For participants who demonstrate a confirmed CR (disappearance of all target lesions) or confirmed PR (at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters) per RECIST v1.1, DOR is defined as the time from first documented evidence of CR or PR until progressive disease (PD) or death due to any cause, whichever occurs first. Per RECIST v1.1, PD is defined as at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also have demonstrated an absolute increase of at least 5 mm. The DOR as determined by ICR based on RECIST v1.1 will be presented.
Measure:DOR per RECIST v1.1, as Determined by INV
Time Frame:Up to ~92 months
Safety Issue:
Description:For participants who demonstrate a confirmed CR (disappearance of all target lesions) or confirmed PR (at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters) per RECIST v1.1, DOR is defined as the time from first documented evidence of CR or PR until PD or death due to any cause, whichever occurs first. Per RECIST v1.1, PD is defined as at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also have demonstrated an absolute increase of at least 5 mm. The DOR as determined by INV based on RECIST v1.1 will be presented.
Measure:Progression-free Survival (PFS) per RECIST v1.1, as Determined by ICR
Time Frame:Up to ~92 months
Safety Issue:
Description:PFS is defined as the time from randomization to the first documented PD or death due to any cause, whichever occurs first. Per RECIST v1.1, PD is defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions is also considered PD. PFS as determined by ICR based on RECIST v1.1 will be presented.
Measure:PFS per RECIST v1.1, as Determined by INV
Time Frame:Up to ~92 months
Safety Issue:
Description:PFS is defined as the time from randomization to the first documented PD or death due to any cause, whichever occurs first. Per RECIST v1.1, PD is defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions is also considered PD. PFS as determined by INV based on RECIST v1.1 will be presented.
Measure:Overall Survival (OS)
Time Frame:Up to ~92 months
Safety Issue:
Description:OS is defined as the time from start of study treatment to death due to any cause.
Measure:Number of Participants Who Experience One or More Adverse Events (AEs)
Time Frame:Up to ~92 months
Safety Issue:
Description:An AE is any untoward medical occurrence in a clinical investigation participant administered a medicinal product and which does not necessarily have a causal relationship with this treatment. The number of participants who experience one or more AEs will be presented.
Measure:Number of Participants who Discontinued Study Treatment Due to an AE
Time Frame:Up to ~92 months
Safety Issue:
Description:An AE is any untoward medical occurrence in a clinical investigation participant administered a medicinal product and which does not necessarily have a causal relationship with this treatment. The number of participants who discontinued study treatment due to an AE will be presented.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Merck Sharp & Dohme Corp.

Last Updated

May 24, 2021