A Study of Tucatinib vs. Placebo in Combination With Ado-trastuzumab Emtansine (T-DM1) for Patients With Advanced or Metastatic HER2+ Breast Cancer
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT03975647|
Recruitment Status : Recruiting
First Posted : June 5, 2019
Last Update Posted : June 2, 2020
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.
|Condition or disease||Intervention/treatment||Phase|
|HER2-positive Breast Cancer||Drug: tucatinib Drug: placebo Drug: T-DM1||Phase 3|
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.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||460 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|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)|
|Actual Study Start Date :||October 2, 2019|
|Estimated Primary Completion Date :||April 30, 2024|
|Estimated Study Completion Date :||April 30, 2024|
|Experimental: Tucatinib + T-DM1||
300mg given twice per day orally
Other Name: ONT-380
3.6 mg/kg given intravenously every 21 days
Other Name: Kadcyla
|Active Comparator: Placebo + T-DM1||
Given twice per day orally
3.6 mg/kg given intravenously every 21 days
Other Name: Kadcyla
- Progression-free survival (PFS) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 by investigator assessment [ Time Frame: Up to approximately 5 years ]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.
- Overall Survival [ Time Frame: Up to approximately 5 years ]OS is defined as the time from randomization to death due to any cause.
- PFS per RECIST v1.1 by blinded independent committee review (BICR) [ Time Frame: Up to approximately 5 years ]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.
- PFS per RECIST v1.1 by investigator assessment in participants with brain metastases at baseline [ Time Frame: Up to approximately 5 years ]
- PFS per RECIST v1.1 by BICR in patients with brain metastases at baseline [ Time Frame: Up to approximately 5 years ]
- Objective response rate (ORR) per RECIST v1.1 by investigator assessment [ Time Frame: Up to approximately 3 years ]ORR is defined as the proportion of subjects with complete response (CR) or partial response (PR) according to RECIST v1.1.
- ORR per RECIST v1.1 by BICR [ Time Frame: Up to approximately 3 years ]
- Duration of response (DOR) per RECIST v1.1 by investigator assessment [ Time Frame: Up to approximately 5 years ]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.
- DOR per RECIST v1.1 by BICR [ Time Frame: Up to approximately 5 years ]
- Clinical benefit rate (CBR) per RECIST v1.1 by investigator assessment [ Time Frame: Up to approximately 3 years ]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.
- CBR per RECIST v1.1 by BICR [ Time Frame: Up to approximately 3 years ]
- Number of participants with adverse events (AEs) [ Time Frame: Through 1 month following last dose; up to approximately 9 months overall per participant ]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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03975647
|Contact: Seattle Genetics Trial Information Supportemail@example.com|
|Study Director:||Evelyn Rustia, MD||Seattle Genetics, Inc.|