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)

Phase 2Active Not RecruitingNCT04721977

Pfizer66 enrolled

Overview

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%.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Breast Cancer

Interventions

Tucatinib

Eligibility

Sex: ALLMin age: 20 Years

Medical Language ↔ Plain English

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

Locations (28)

Aichi Cancer Center Hospital ( Site 1013)

Nagoya, Aichi-ken, Japan

Nagoya University Hospital ( Site 1021)

Nagoya, Aichi-ken, Japan

National Cancer Center Hospital East ( Site 1002)

Kashiwa, Chiba, Japan

National Hospital Organization Shikoku Cancer Center ( Site 1014)

Matsuyama, Ehime, Japan

National Hospital Organization Hokkaido Cancer Center ( Site 1017)

Sapporo, Hokkaido, Japan

Outcomes

Primary Outcomes

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

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.

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)

Secondary Outcomes

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

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.

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

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

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.

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

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

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

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.

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

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

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

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

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

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.

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

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

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

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

Overall Survival: All Participants

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.

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

Overall Survival: Japanese Participants

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

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

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.