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)

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

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 Overview

• Status: Active, not recruiting
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: Tucatinib; Biological: Trastuzumab; Drug: Capecitabine

• Study Type: Interventional
• Enrollment (Actual): 66
• Phase: Phase 2

Contacts and Locations

Study Locations

• Japan
  • Fukuoka, Japan, 811-1395
    • National Hospital Organization Kyushu Cancer Center ( Site 1009)
  • Fukushima, Japan, 960-1295
    • Fukushima Medical University Hospital ( Site 1012)
  • Hiroshima, Japan, 730-8518
    • Hiroshima City Hiroshima Citizens Hospital ( Site 1024)
  • Kagoshima, Japan, 892-0833
    • Social medical corporation Hakuaikai Sagara Hospital ( Site 1008)
  • Kumamoto, Japan, 862-8655
    • Kumamoto Shinto General Hospital ( Site 1007)
  • Osaka, Japan, 540-0006
    • National Hospital Organization Osaka National Hospital ( Site 1001)
  • Osaka, Japan, 541-8567
    • Osaka International Cancer Institute ( Site 1004)
  • Tokyo, Japan, 104-0045
    • National Cancer Center Hospital ( Site 1003)
  • Tokyo, Japan, 113-0033
    • Juntendo University Hospital ( Site 1025)
  • Tokyo, Japan, 135-8550
    • The Cancer Institute Hospital of JFCR ( Site 1015)
  • Tokyo, Japan, 142-8666
    • Showa University Hospital ( Site 1023)
  • Tokyo, Japan, 160-0023
    • Tokyo Medical University Hospital ( Site 1006)
  • Aichi
    • Nagoya, Aichi, Japan, 464-8681
      • Aichi Cancer Center Hospital ( Site 1013)
    • Nagoya, Aichi, Japan, 466-8560
      • Nagoya University Hospital ( Site 1021)
  • Chiba
    • Kashiwa, Chiba, Japan, 2778577
      • National Cancer Center Hospital East ( Site 1002)
  • Ehime
    • Matsuyama, Ehime, Japan, 791-0280
      • National Hospital Organization Shikoku Cancer Center ( Site 1014)
  • Hokkaido
    • Sapporo, Hokkaido, Japan, 003-0804
      • National Hospital Organization Hokkaido Cancer Center ( Site 1017)
    • Sapporo, Hokkaido, Japan, 060-8648
      • Hokkaido University Hospital ( Site 1022)
  • Hyogo
    • Akashi, Hyogo, Japan, 673-8558
      • Hyogo Cancer Center ( Site 1005)
    • Nishinomiya, Hyogo, Japan, 663-8501
      • Hyogo College of Medicine Hospital ( Site 1019)
  • Ibaraki
    • Tsukuba, Ibaraki, Japan, 305-8576
      • University of Tsukuba Hospital ( Site 1020)
  • Kanagawa
    • Yokohama, Kanagawa, Japan, 241-8515
      • Kanagawa Cancer Center ( Site 1010)
  • Okinawa
    • Naha, Okinawa, Japan, 901-0154
      • Medical Corporation Nahanishikai Nahanishi Clinic ( Site 1016)
  • Saitama
    • Kitaadachi-gun, Saitama, Japan, 362-0806
      • Saitama Cancer Center ( Site 1018)
• Korea, Republic of
  • Seoul, Korea, Republic of, 03080
    • Seoul National University Hospital ( Site 2003)
  • Seoul, Korea, Republic of, 03722
    • Severance Hospital ( Site 2001)
  • Seoul, Korea, Republic of, 06351
    • Samsung Medical Center ( Site 2002)
• Taiwan
  • Tainan
    • Taiwan, Tainan, Taiwan, 704
      • National Cheng Kung University Hospital ( Site 3000)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Tucatinib + Trastuzumab + Capecitabine; Participants 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.

Drug: Tucatinib; Tucatinib 300 mg administered BID via oral tablet; Other Names: MK-7119; Tukysa; Biological: Trastuzumab; Trastuzumab 8 mg/kg loading dose followed by 6 mg/kg maintenance dose, administered via IV infusion; Other Names: Herceptin; Herceptin Hylecta; Drug: Capecitabine; Capecitabine 1000 mg/m^2 administered BID via oral tablet; Other Names: Xeloda

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)	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.	Up to ~21 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
cORR per RECIST v1.1, as Determined by Investigator Assessment (INV)	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.	Up to ~92 months
Duration of Response (DOR) per RECIST v1.1, as Determined by ICR	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.	Up to ~92 months
DOR per RECIST v1.1, as Determined by INV	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.	Up to ~92 months
Progression-free Survival (PFS) per RECIST v1.1, as Determined by ICR	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.	Up to ~92 months
PFS per RECIST v1.1, as Determined by INV	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.	Up to ~92 months
Overall Survival (OS)	OS is defined as the time from start of study treatment to death due to any cause.	Up to ~92 months
Number of Participants Who Experience One or More Adverse Events (AEs)	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.	Up to ~92 months
Number of Participants who Discontinued Study Treatment Due to an AE	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.	Up to ~92 months

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC
• Investigators: Study Director: Medical Director, Merck Sharp & Dohme LLC

Publications and helpful links

Helpful Links

• Merck Clinical Trials Information

Study record dates

Study Major Dates

• Study Start (Actual): April 8, 2021
• Primary Completion (Actual): July 17, 2023
• Study Completion (Estimated): December 6, 2028

Study Registration Dates

• First Submitted: January 20, 2021
• First Submitted That Met QC Criteria: January 20, 2021
• First Posted (Actual): January 25, 2021

Study Record Updates

• Last Update Posted (Estimated): February 23, 2024
• Last Update Submitted That Met QC Criteria: February 22, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Antineoplastic Agents, Immunological; Protein Kinase Inhibitors; Trastuzumab; Capecitabine; Tucatinib
• Other Study ID Numbers: 7119-001; MK-7119-001 (Other Identifier: Merck); jRCT2051200152 (Registry Identifier: jRCT)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes