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.
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
Drug | Synonyms | Arms |
---|
tucatinib | ONT-380 | Tucatinib + T-DM1 |
placebo | | Placebo + T-DM1 |
T-DM1 | Kadcyla | Placebo + 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
Name | Type | Description | Interventions |
---|
Tucatinib + T-DM1 | Experimental | Tucatinib + T-DM1 | |
Placebo + T-DM1 | Active Comparator | Placebo + T-DM1 | |
Eligibility Criteria
- Inclusion Criteria:
- Histologically confirmed HER2+ 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 locally advanced/metastatic breast cancer after
last systemic therapy, or be intolerant of last systemic therapy
- Measurable or non-measurable disease assessable by RECIST v1.1
- ECOG performance status score of 0 or 1
- 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 or
previously treated and progressing 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, afatinib, trastuzumab deruxtecan (DS-8201a), or
any other investigational anti-HER2, anti-EGFR, or HER2 TKI agent. Prior
treatment with lapatinib or neratinib within 12 months of starting study
treatment (except in cases where they were given for ≤21 days and was
discontinued for reasons other than disease progression or severe toxicity).
Prior treatment with pyrotinib for recurrent of mBC (except in cases where
pyrotinib was given for ≤21 days and was discontinued for reasons other than
disease progression or severe toxicity).
- 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: | Seagen Inc. |
Trial Keywords
Last Updated
August 24, 2021