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NCT Number: NCT04721977

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)

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%.

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This study is active but is not currently recruiting participants.

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Key information

Conditions

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

Age range

20 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Aichi Cancer Center Hospital ( Site 1013), Nagoya, Aichi-ken, Japan

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Tucatinib

Drug

Tucatinib 300 mg administered BID via oral tablet

Other names: MK-7119, Tukysa

trastuzumab

Biological

Trastuzumab 8 mg/kg loading dose followed by 6 mg/kg maintenance dose, administered via IV infusion

Other names: Herceptin, Herceptin Hylecta

Capecitabine

Drug

Capecitabine 1000 mg/m^2 administered BID via oral tablet

Other names: Xeloda

Primary outcomes

  1. Confirmed Objective Response Rate(cORR) Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 Determined by Independent Central Review (ICR): Japanese Participants

    Time frame: From date of first dose until first documented disease progression or start of new anticancer therapy, whichever occurred first (maximum up to 17.8 months)

    cORR was defined as percentage of participants with confirmed complete response (CR) or partial response (PR), per RECIST version 1.1. CR: disappearance of all target lesions. Any pathological lymph nodes must have a reduction in short axis to <10 millimeter(mm). PR: a >=30% decrease in the sum of diameters of target lesions, taking as a reference the baseline sum diameters. Only response assessments before first documented progressive disease(PD) or new anti-cancer therapies were considered. PD: at least a 20% increase in sum of diameters of target lesions, taking as reference the smallest sum on study(included baseline sum if smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Appearance of one or more new lesions was also considered PD. Participants with missing data were considered non-responders. cORR was determined by ICR. Two-sided 90% exact confidence interval was based on Clopper-Pearson method.

Secondary outcomes

  1. Confirmed Objective Response Rate(cORR) Per RECIST Version 1.1 Determined by ICR: All Participants

    Time frame: From date of first dose until first documented disease progression or start of new anticancer therapy, whichever occurred first

    cORR was defined as percentage of participants with confirmed CR or PR, per RECIST version 1.1. CR: disappearance of all target lesions. Any pathological lymph nodes must have a reduction in short axis to <10 mm. PR: a >=30% decrease in the sum of diameters of target lesions, taking as a reference the baseline sum diameters. Only response assessments before first documented PD or new anti-cancer therapies were considered. PD: at least a 20% increase in sum of diameters of target lesions, taking as reference the smallest sum on study (included baseline sum if smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Appearance of one or more new lesions was also considered PD. Participants with missing data were considered non-responders. cORR was determined by ICR. Two-sided 90% exact confidence interval was based on Clopper-Pearson method.

  2. Confirmed Objective Response Rate(cORR) Per RECIST Version 1.1 Determined by Investigator Assessment (INV): Japanese Participants

    Time frame: From date of first dose until first documented disease progression or start of new anticancer therapy, whichever occurred first

    cORR was defined as percentage of participants with confirmed CR or PR, per RECIST version 1.1. CR: disappearance of all target lesions. Any pathological lymph nodes must have a reduction in short axis to <10 mm. PR: a >=30% decrease in the sum of diameters of target lesions, taking as a reference the baseline sum diameters. Only response assessments before first documented PD or new anti-cancer therapies were considered. PD: at least a 20% increase in sum of diameters of target lesions, taking as reference the smallest sum on study (included baseline sum if smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Appearance of one or more new lesions was also considered PD. Participants with missing data were considered non-responders. cORR was determined by INV. Two-sided 90% exact confidence interval was based on Clopper-Pearson method.

  3. Confirmed Objective Response Rate(cORR) Per RECIST Version 1.1 Determined by INV: All Participants

    Time frame: From date of first dose until first documented disease progression or start of new anticancer therapy, whichever occurred first

    cORR was defined as percentage of participants with confirmed CR or PR, per RECIST version 1.1. CR: disappearance of all target lesions. Any pathological lymph nodes must have a reduction in short axis to <10 mm. PR: a >=30% decrease in the sum of diameters of target lesions, taking as a reference the baseline sum diameters. Only response assessments before first documented PD or new anti-cancer therapies were considered. PD: at least a 20% increase in sum of diameters of target lesions, taking as reference the smallest sum on study (included baseline sum if smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Appearance of one or more new lesions was also considered PD. Participants with missing data were considered non-responders. cORR was determined by ICR. Two-sided 90% exact confidence interval was based on Clopper-Pearson method.

  4. Duration of Response (DOR) Per RECIST Version 1.1 Determined by INV: All Participants

    Time frame: From date of first objective response (CR or PR that is subsequently confirmed) to documented PD, or death from any cause whichever occurred first

    DOR was defined as the time from the first objective response (CR or PR that is subsequently confirmed) to documented PD per RECIST version 1.1 or death from any cause, whichever occurred first. CR: disappearance of all target lesions. Any pathological lymph nodes must have a reduction in short axis to <10 mm. PR: a >=30% decrease in the sum of diameters of target lesions, taking as a reference the baseline sum diameters. Only response assessments before first documented PD or new anti-cancer therapies were considered. PD: at least a 20% increase in sum of diameters of target lesions, taking as reference the smallest sum on study (included baseline sum if smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Appearance of one or more new lesions was also considered PD. Only those participants who achieved a confirmed response will be included in the analysis. DOR was determined by INV.

  5. Duration of Response (DOR) Per RECIST Version 1.1 Determined by INV: Japanese Participants

    Time frame: From date of first objective response (CR or PR that is subsequently confirmed) to documented PD, or death from any cause whichever occurred first

    DOR was defined as the time from the first objective response (CR or PR that is subsequently confirmed) to documented PD per RECIST version 1.1 or death from any cause, whichever occurred first. CR: disappearance of all target lesions. Any pathological lymph nodes must have a reduction in short axis to <10 mm. PR: a >=30% decrease in the sum of diameters of target lesions, taking as a reference the baseline sum diameters. Only response assessments before first documented PD or new anti-cancer therapies were considered. PD: at least a 20% increase in sum of diameters of target lesions, taking as reference the smallest sum on study (included baseline sum if smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Appearance of one or more new lesions was also considered PD. Only those participants who achieved a confirmed response will be included in the analysis. DOR was determined by INV.

  6. Duration of Response (DOR) Per RECIST Version 1.1 Determined by ICR: All Participants

    Time frame: From date of first objective response (CR or PR that is subsequently confirmed) to documented PD, or death from any cause whichever occurred first

    DOR was defined as the time from the first objective response (CR or PR that is subsequently confirmed) to documented PD per RECIST version 1.1 or death from any cause, whichever occurred first. CR: disappearance of all target lesions. Any pathological lymph nodes must have a reduction in short axis to <10 mm. PR: a >=30% decrease in the sum of diameters of target lesions, taking as a reference the baseline sum diameters. Only response assessments before first documented PD or new anti-cancer therapies were considered. PD: at least a 20% increase in sum of diameters of target lesions, taking as reference the smallest sum on study (included baseline sum if smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Appearance of one or more new lesions was also considered PD. Only those participants who achieved a confirmed response will be included in the analysis. DOR was determined by ICR.

  7. Duration of Response (DOR) Per RECIST Version 1.1 Determined by ICR: Japanese Participants

    Time frame: From date of first objective response (CR or PR that is subsequently confirmed) to documented PD, or death from any cause whichever occurred first

    DOR was defined as the time from the first objective response (CR or PR that is subsequently confirmed) to documented PD per RECIST version 1.1 or death from any cause, whichever occurred first. CR: disappearance of all target lesions. Any pathological lymph nodes must have a reduction in short axis to <10 mm. PR: a >=30% decrease in the sum of diameters of target lesions, taking as a reference the baseline sum diameters. Only response assessments before first documented PD or new anti-cancer therapies were considered. PD: at least a 20% increase in sum of diameters of target lesions, taking as reference the smallest sum on study (included baseline sum if smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Appearance of one or more new lesions was also considered PD. Only those participants who achieved a confirmed response will be included in the analysis. DOR was determined by ICR.

  8. Progression Free Survival (PFS) Per RECIST Version 1.1 Determined by ICR: All Participants

    Time frame: From date of first dose to the date of documented disease progression or death from any cause whichever occurred first or censoring date

    PFS time was defined as the time from the first date of study treatment to the date of documented disease progression using RECIST v1.1 or death from any cause, whichever occurred first. Participants who were alive and had not progressed at the time of the analysis were censored at the time of their last tumor assessment documenting absence of PD. Participants lacking an evaluation of tumor response after their start of study treatment had their event time censored at 1 day. PD: at least a 20% increase in sum of diameters of target lesions, taking as reference the smallest sum on study (included baseline sum if smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Appearance of one or more new lesions was also considered PD. PFS was determined by ICR.

  9. Progression Free Survival (PFS) Per RECIST Version 1.1 Determined by ICR: Japanese Participants

    Time frame: From date of first dose to the date of documented disease progression or death from any cause whichever occurred first or censoring date

    PFS time was defined as the time from the first date of study treatment to the date of documented disease progression using RECIST v1.1 or death from any cause, whichever occurred first. Participants who were alive and had not progressed at the time of the analysis were censored at the time of their last tumor assessment documenting absence of PD. Participants lacking an evaluation of tumor response after their start of study treatment had their event time censored at 1 day. PD: at least a 20% increase in sum of diameters of target lesions, taking as reference the smallest sum on study (included baseline sum if smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Appearance of one or more new lesions was also considered PD. PFS was determined by ICR.

  10. Progression Free Survival (PFS) Per RECIST Version 1.1 Determined by INV: All Participants

    Time frame: From date of first dose to the date of documented disease progression or death from any cause whichever occurred first or censoring date

    PFS time was defined as the time from the first date of study treatment to the date of documented disease progression using RECIST v1.1 or death from any cause, whichever occurred first. Participants who were alive and had not progressed at the time of the analysis were censored at the time of their last tumor assessment documenting absence of PD. Participants lacking an evaluation of tumor response after their start of study treatment had their event time censored at 1 day. PD: at least a 20% increase in sum of diameters of target lesions, taking as reference the smallest sum on study (included baseline sum if smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Appearance of one or more new lesions was also considered PD. PFS was determined by INV.

  11. Progression Free Survival (PFS) Per RECIST Version 1.1 Determined by INV: Japanese Participants

    Time frame: From date of first dose to the date of documented disease progression or death from any cause whichever occurred first or censoring date

    PFS time was defined as the time from the first date of study treatment to the date of documented disease progression using RECIST v1.1 or death from any cause, whichever occurred first. Participants who were alive and had not progressed at the time of the analysis were censored at the time of their last tumor assessment documenting absence of PD. Participants lacking an evaluation of tumor response after their start of study treatment had their event time censored at 1 day. PD: at least a 20% increase in sum of diameters of target lesions, taking as reference the smallest sum on study (included baseline sum if smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Appearance of one or more new lesions was also considered PD. PFS was determined by INV.

  12. Overall Survival: All Participants

    Time frame: From start of study treatment to date of death from any cause or censoring date

    OS was defined as the time from start of study treatment to date of death due to any cause. In the absence of confirmation of death, survival time was censored at the last date the participant was known to be alive. Participants lacking data beyond their start of study treatment had their survival time censored at 1 day.

  13. Overall Survival: Japanese Participants

    Time frame: From start of study treatment to date of death from any cause or censoring date

    OS was defined as the time from start of study treatment to date of death due to any cause. In the absence of confirmation of death, survival time was censored at the last date the participant was known to be alive. Participants lacking data beyond their start of study treatment had their survival time censored at 1 day.

  14. Number of Participants With Adverse Events, Serious Adverse Events and Treatment Related Adverse Events and Serious Adverse Events: All Participants

    Time frame: From date of first dose of study treatment to up to 30 days after last dose of study treatment

    An adverse event was defined as any untoward medical occurrence in a participant or clinical investigational participant administered a medicinal product and which does not necessarily have a causal relationship with this treatment. Serious adverse event was any untoward medical occurrence at any dose that resulted in death; life-threatening (immediate risk of death); required inpatient hospitalization or prolongation of existing hospitalization; persistent or significant disability/incapacity (substantial disruption of the ability to conduct normal life functions); congenital anomaly/birth defect or that was considered as an important medical event. Treatment related adverse events and serious adverse events was judged by investigator.

  15. Number of Participants With Adverse Events, Serious Adverse Events and Treatment Related Adverse Events and Serious Adverse Events: Japanese Participants

    Time frame: From date of first dose of study treatment to up to 30 days after last dose of study treatment

    An adverse event was defined as any untoward medical occurrence in a participant or clinical investigational participant administered a medicinal product and which does not necessarily have a causal relationship with this treatment. t intervention indicated and Grade 5 indicates death related to AE. Participants who discontinued treatment due to AEs were captured under AEs leading to treatment discontinuation. SAE was any untoward medical occurrence at any dose that resulted in death; life-threatening (immediate risk of death); required inpatient hospitalization or prolongation of existing hospitalization; persistent or significant disability/incapacity (substantial disruption of the ability to conduct normal life functions); congenital anomaly/birth defect or that was considered as an important medical event. Treatment related adverse events and serious adverse events was judged by investigator.

  16. Number of Participants With Abnormalities in Laboratory Parameters: All Participants

    Time frame: From date of first dose of study treatment to up to 30 days after last dose of study treatment

  17. Number of Participants With Abnormalities in Laboratory Parameters: Japanese Participants

    Time frame: From date of first dose of study treatment to up to 30 days after last dose of study treatment

  18. Number of Participants With Dose Modifications and Treatment Discontinuations: All Participants

    Time frame: From date of first dose of study treatment to up to 30 days after last dose of study treatment

  19. Number of Participants With Dose Modifications and Treatment Discontinuations: Japanese Participants

    Time frame: From date of first dose of study treatment to up to 30 days after last dose of study treatment

  20. Number of Participants With Clinically Significant Changes in Vital Signs: All Participants

    Time frame: From date of first dose of study treatment to up to 30 days after last dose of study treatment

  21. Number of Participants With Clinically Significant Changes in Vital Signs: Japanese Participants

    Time frame: From date of first dose of study treatment to up to 30 days after last dose of study treatment

Sponsors and collaborators

Lead sponsor

Pfizer

Industry

Registry information

Official study 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

Important dates

Study start
2021
Primary completion
2023
Study completion
2026
First posted
Jan 25, 2021
Registry last updated
Jan 9, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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