Clinical Trials /

A Study of Tucatinib vs. Placebo in Combination With Ado-trastuzumab Emtansine (T-DM1) for Patients With Advanced or Metastatic HER2+ Breast Cancer

NCT03975647

Description:

This study is being done to see if tucatinib with ado-trastuzumab emtansine (T-DM1) works better than T-DM1 alone to help patients who have a specific type of breast cancer called HER2 positive breast carcinoma. The breast cancer in this study is either metastatic (spread into other parts of the body) or cannot be removed completely with surgery. Patients in this study will be randomly assigned to get either tucatinib or placebo (a pill with no medicine). This is a blinded study, so neither patients nor their doctors will know whether a patient gets tucatinib or placebo. All patients in the study will get T-DM1, a drug that is often used to treat this cancer. Each treatment cycle lasts 21 days. Patients will swallow tucatinib pills or placebo pills two times every day. Patients will get T-DM1 injections from the study site staff on the first day of every cycle.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: A Study of Tucatinib vs. Placebo in Combination With Ado-trastuzumab Emtansine (T-DM1) for Patients With Advanced or Metastatic HER2+ Breast Cancer
  • Official Title: Randomized, Double-blind, Phase 3 Study of Tucatinib or Placebo in Combination With Ado-trastuzumab Emtansine (T-DM1) for Subjects With Unresectable Locally-advanced or Metastatic HER2+ Breast Cancer (HER2CLIMB-02)

Clinical Trial IDs

  • ORG STUDY ID: SGNTUC-016
  • NCT ID: NCT03975647

Conditions

  • HER2-positive Breast Cancer

Interventions

DrugSynonymsArms
tucatinibONT-380Tucatinib + T-DM1
placeboPlacebo + T-DM1
T-DM1KadcylaPlacebo + T-DM1

Purpose

This study is being done to see if tucatinib with ado-trastuzumab emtansine (T-DM1) works better than T-DM1 alone to help patients who have a specific type of breast cancer called HER2 positive breast carcinoma. The breast cancer in this study is either metastatic (spread into other parts of the body) or cannot be removed completely with surgery. Patients in this study will be randomly assigned to get either tucatinib or placebo (a pill with no medicine). This is a blinded study, so neither patients nor their doctors will know whether a patient gets tucatinib or placebo. All patients in the study will get T-DM1, a drug that is often used to treat this cancer. Each treatment cycle lasts 21 days. Patients will swallow tucatinib pills or placebo pills two times every day. Patients will get T-DM1 injections from the study site staff on the first day of every cycle.

Detailed Description

      This study is designed to evaluate the efficacy and safety of tucatinib in combination with
      T-DM1 in subjects with unresectable locally-advanced or metastatic HER2+ breast cancer who
      have had prior treatment with a taxane and trastuzumab in any setting. Prior pertuzumab
      treatment is permitted, but not required. Subjects will be randomized in a 1:1 manner to
      receive 21-day cycles of either tucatinib or placebo in combination with T-DM1.

      While on study treatment, subjects will be assessed for progression every 6 weeks for the
      first 24 weeks, and every 9 weeks thereafter, irrespective of dose holds or interruptions.
      Study treatment will continue until unacceptable toxicity, disease progression, withdrawal of
      consent, or study closure. After completion of study treatment and after occurrence of
      disease progression, subjects in both arms of the study will continue to be followed for
      survival until study closure or withdrawal of consent.
    

Trial Arms

NameTypeDescriptionInterventions
Tucatinib + T-DM1Experimental
  • tucatinib
  • T-DM1
Placebo + T-DM1Active Comparator
  • placebo
  • T-DM1

Eligibility Criteria

        -  Inclusion Criteria:

               -  Histologically confirmed HER2+ metastatic breast carcinoma as determined by a
                  sponsor-designated central laboratory

               -  History of prior treatment with a taxane and trastuzumab in any setting,
                  separately or in combination

               -  Have progression of unresectable LA/M breast cancer after last systemic therapy,
                  or be intolerant of last systemic therapy

               -  Measurable or non-measurable disease assessable by RECIST v1.1

               -  Hormone receptor (estrogen receptor/progesterone receptor) status must be known
                  prior to randomization

               -  ECOG performance status score of 0 or 1

               -  Life expectancy ≥6 months

               -  CNS Inclusion - Based on screening contrast brain magnetic resonance imaging
                  (MRI), subjects must have at least one of the following:

                  (a) No evidence of brain metastases

                  (b) Untreated brain metastases not needing immediate local therapy

                  (c) Previously treated brain metastases

                    1. Brain metastases previously treated with local therapy may either be stable
                       since treatment or may have progressed since prior local CNS therapy,
                       provided that there is no clinical indication for immediate re-treatment
                       with local therapy

                    2. Subjects treated with CNS local therapy for newly identified lesions may be
                       eligible to enroll if all of the following criteria are met:

                       (i) Time since SRS is at least 7 days prior to first dose of study
                       treatment, time since WBRT is at least 21 days prior to first dose, or time
                       since surgical resection is at least 28 days.

                       (ii) Other sites of evaluable disease are present

                    3. Relevant records of any CNS treatment must be available to allow for
                       classification of target and non-target lesions

          -  Exclusion Criteria:

               -  Prior treatment with tucatinib, neratinib, afatinib, trastuzumab deruxtecan
                  (DS-8201a), or any other investigational anti-HER2, anti-EGFR, or HER2 TKI agent.
                  Prior treatment with lapatinib within 12 months of starting study treatment
                  (except in cases where lapatinib was given for <21 days and was discontinued for
                  reasons other than disease progression or severe toxicity).

               -  Prior treatment with T-DM1

               -  Treatment with any systemic anti-cancer therapy (including hormonal therapy),
                  non-CNS radiation, experimental agent or participation in another interventional
                  clinical trial ≤3 weeks prior to first dose of study treatment

               -  Any toxicity related to prior cancer therapies that has not resolved to ≤ Grade
                  1, with the following exceptions:

                    1. Alopecia;

                    2. Neuropathy, which must have resolved to ≤ Grade 2;

                    3. Congestive heart failure (CHF), which must have been ≤ Grade 1 in severity
                       at the time of occurrence, and must have resolved completely

               -  Clinically significant cardiopulmonary disease

               -  Myocardial infarction or unstable angina within 6 months prior to first dose of
                  study treatment

               -  Carrier of Hepatitis A or Hepatitis C or has other known chronic liver disease

               -  Positive for human immunodeficiency virus (HIV)

               -  Subjects who are pregnant, breastfeeding, or planning to become pregnant from
                  time of informed consent until 7 months following the last dose of study drug

               -  Unable to swallow pills or has significant gastrointestinal disease which would
                  preclude the adequate oral absorption of medications

               -  Use of a strong CYP3A4 or CYP2C8 inhibitor within 2 weeks, or use of a strong
                  CYP3A4 or CYP2C8 inducer within 5 days prior to the first dose of study treatment

               -  CNS Exclusion - Based on screening contrast brain magnetic resonance imaging
                  (MRI), subjects must not have any of the following:

                    1. Any untreated brain lesions >2 cm in size

                    2. Ongoing use of corticosteroids for control of symptoms of brain metastases
                       at a total daily dose of >2 mg of dexamethasone (or equivalent).

                    3. Any brain lesion thought to require immediate local therapy

                    4. Known or concurrent leptomeningeal disease as documented by the investigator

                    5. Poorly controlled generalized or complex partial seizures
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Progression-free survival (PFS) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 by investigator assessment
Time Frame:Up to approximately 5 years
Safety Issue:
Description:PFS per investigator is defined as the time from the date of randomization to the investigator assessment of disease progression according to RECIST v1.1 or death from any cause, whichever occurs first.

Secondary Outcome Measures

Measure:Overall Survival
Time Frame:Up to approximately 5 years
Safety Issue:
Description:OS is defined as the time from randomization to death due to any cause.
Measure:PFS per RECIST v1.1 by blinded independent committee review (BICR)
Time Frame:Up to approximately 5 years
Safety Issue:
Description:PFS per BICR is defined as the time from the date of randomization to the centrally-reviewed documented disease progression according to RECIST v1.1 or death from any cause, whichever occurs first.
Measure:PFS per RECIST v1.1 by investigator assessment in participants with brain metastases at baseline
Time Frame:Up to approximately 5 years
Safety Issue:
Description:
Measure:PFS per RECIST v1.1 by BICR in patients with brain metastases at baseline
Time Frame:Up to approximately 5 years
Safety Issue:
Description:
Measure:Objective response rate (ORR) per RECIST v1.1 by investigator assessment
Time Frame:Up to approximately 3 years
Safety Issue:
Description:ORR is defined as the proportion of subjects with complete response (CR) or partial response (PR) according to RECIST v1.1.
Measure:ORR per RECIST v1.1 by BICR
Time Frame:Up to approximately 3 years
Safety Issue:
Description:
Measure:Duration of response (DOR) per RECIST v1.1 by investigator assessment
Time Frame:Up to approximately 5 years
Safety Issue:
Description:DOR is defined as the time from first documentation of objective response to the first documentation of disease progression or death from any cause, whichever occurs earlier.
Measure:DOR per RECIST v1.1 by BICR
Time Frame:Up to approximately 5 years
Safety Issue:
Description:
Measure:Clinical benefit rate (CBR) per RECIST v1.1 by investigator assessment
Time Frame:Up to approximately 3 years
Safety Issue:
Description:CBR is defined as the proportion of subjects with stable disease (SD) or non-CR or non-PD for ≥6 months or best response of CR or PR according to RECIST v1.1.
Measure:CBR per RECIST v1.1 by BICR
Time Frame:Up to approximately 3 years
Safety Issue:
Description:
Measure:Number of participants with adverse events (AEs)
Time Frame:Through 1 month following last dose; up to approximately 9 months overall per participant
Safety Issue:
Description:An AE is any untoward medical occurrence in a subject or clinical investigational subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment.

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Seattle Genetics, Inc.

Last Updated

January 16, 2020