Trial · NCT03975647
A Study of Tucatinib vs. Placebo in Combination With Ado-trastuzumab Emtansine (T-DM1) for Patients With Advanced or Metastatic HER2+ Breast Cancer
NCT03975647, Phase 3, Active not recruiting, Seagen, a wholly owned subsidiary of Pfizer; results first posted 2024-07-30
3 sourcestrials-2026-11-12-0.5.0
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ConductScience Library. A Study of Tucatinib vs. Placebo in Combination With Ado-trastuzumab Emtansine (T-DM1) for Patients With Advanced or Metastatic HER2+ Breast Cancer. Trials, record NCT03975647. Release trials-2026-11-12-0.5.0, 12 Nov 2026. https://conductscience.org/library/trials/NCT03975647
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Trial
As registered on ClinicalTrials.gov, in the graph's capture of the registry.
- Title
- A Study of Tucatinib vs. Placebo in Combination With Ado-trastuzumab Emtansine (T-DM1) for Patients With Advanced or Metastatic HER2+ Breast Cancer
- NCT number
- NCT03975647
- Status
- Active not recruiting
- Phases
- Phase 3
- Enrollment
- 466 participants, actual
- Lead sponsor
- Seagen, a wholly owned subsidiary of Pfizer
- Conditions
- HER2-positive Breast Cancer
- Interventions
- tucatinib, placebo, T-DM1
- First posted
- 2019-06-05
- Last updated
- 2026-07-23
- Results first posted
- 2024-07-30
Source ClinicalTrials.gov
Registered outcomes13
Each outcome the trial registered, primary first, in ClinicalTrials.gov's words.
| List | Outcome | Time frame | Description |
|---|---|---|---|
| Primary | Progression-Free Survival (PFS) as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version (v)1.1 Based on Investigator Assessment | From the date of randomization to the date of PD or death from any cause or censoring date, whichever occurred first (maximum up to 43 months) | PFS as per investigator was defined as the time from the date of randomization to the investigator assessment of disease progression (PD) as per RECIST v1.1 or death from any cause, whichever occurred first. PD: at least a 20 percent (%) increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 millimiter (mm). Participants without documentation of PD, or death at the time of analysis were censored at the date of the last tumor assessment. |
| Secondary | Overall Survival (OS) | Up to approximately 5 years | OS was defined as the time from randomization to death due to any cause. For a participant who was not known to have died by the end of study follow-up, observation of OS was censored on the date the participant was last known to be alive (i.e., the date of last contact). |
| Secondary | Progression-Free Survival as Per RECIST v1.1 in Participants With Brain Metastases at Baseline Based on Investigator Assessment | From the date of randomization to the date of PD or death from any cause or censoring date, whichever occurred first (maximum up to 45 months) | PFS as per investigator was defined as the time from the date of randomization to the investigator assessment of PD as per RECIST v1.1 or death from any cause, whichever occurred first. PD: at least a 20 % increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Participants without documentation of PD, or death at the time of analysis were censored at the date of the last tumor assessment. PFS was analyzed in participants with presence or history of brain metastases. |
| Secondary | Objective Response Rate (ORR) as Per RECIST v1.1 Based on Investigator Assessment | From the date of first CR or PR until the date of the first documentation of PD or death, whichever occurred first (maximum up to 43 months) | ORR was defined as the percentage of participants with confirmed complete response (CR) or partial response (PR) according to RECIST v1.1. CR: disappearance of all target lesions. Any pathological lymph nodes must have reduction in short axis to less than (\<)10 mm. PR: a greater than equal (\>=) 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. For a response to be considered as confirmed, the subsequent response needs to be at least 4 weeks after the initial response. ORR by investigator assessment is based on investigator response assessments. Two-sided 95% exact confidence interval, computed using the Clopper-Pearson method. |
| Secondary | Overall Survival in Participants With Brain Metastases at Baseline | Up to approximately 5 years | OS was defined as the time from randomization to death due to any cause. For a participant who was not known to have died by the end of study follow-up, observation of OS was censored on the date the participant was last known to be alive (i.e., the date of last contact). OS was analyzed in participants with presence or history of brain metastases. |
| Secondary | Progression-Free Survival as Per RECIST v1.1 Determined by Blinded Independent Committee Review (BICR) | From the date of randomization to the date of PD or death from any cause or censoring date, whichever occurred first (maximum up to 43 months) | PFS as per BICR was defined as the time from the date of randomization to the centrally-reviewed documented PD as per RECIST v1.1 or death from any cause, whichever occurred first. PD: at least a 20 % increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Participants without documented progression of PD or death at the time of analysis were censored at the date of the last tumor assessment. |
| Secondary | Progression-Free Survival in Participants With Brain Metastases at Baseline as Per RECIST v1.1 Determined by BICR | From the date of randomization to the date of PD or death from any cause or censoring date, whichever occurred first (maximum up to 43 months) | PFS as per BICR was defined as the time from the date of randomization to the centrally-reviewed documented PD as per RECIST v1.1 or death from any cause, whichever occurred first. PD: at least a 20 % increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. PFS was analyzed in participants with presence or history of brain metastases. |
| Secondary | Objective Response Rate as Per RECIST v1.1 Determined by BICR | From the date of randomization to the date of PD or death from any cause or censoring date, whichever occurred first (maximum up to 43 months) | ORR was defined as the percentage of participants with confirmed CR or PR according to RECIST v1.1. CR: Disappearance of all target lesions. Any pathological lymph nodes must have reduction in short axis to \<10 mm. PR: A \>= 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. ORR per BICR is based on BICR response assessments. |
| Secondary | Duration of Response (DOR) as Per RECIST v1.1 Based on Investigator Assessment | Up to approximately 5 years | DOR was defined as the time from first documentation of objective response (CR or PR that is subsequently confirmed) to the first documentation of PD as per RECIST v1.1 PD: at least a 20 % increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Participants without documentation of PD, or death at the time of analysis were censored at the date of the last tumor assessment. CR: disappearance of all target lesions. Any pathological lymph nodes must have reduction in short axis to \<10 mm. PR: A\>=30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. DOR per investigator was based on investigator response assessments. |
| Secondary | Duration of Response as Per RECIST v1.1 by BICR | Up to approximately 5 years | DOR was defined as the time from first documentation of objective response (CR or PR that is subsequently confirmed) to the first documentation of PD as per RECIST v1.1 PD: at least a 20 % increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Participants without documentation of PD, or death at the time of analysis were censored at the date of the last tumor assessment. CR: disappearance of all target lesions. Any pathological lymph nodes must have reduction in short axis to \<10 mm. PR: A\>=30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. DOR per BICR was based on BICR response assessments. |
1 to 10 of 13Source ClinicalTrials.gov
See all 13 registered outcomesOutcomes13
Each outcome the trial posted results for, in ClinicalTrials.gov's words.
| Type | Outcome | Time frame | Population | Units | Measured as |
|---|---|---|---|---|---|
| PRIMARY | Progression-Free Survival (PFS) as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version (v)1.1 Based on Investigator Assessment | From the date of randomization to the date of PD or death from any cause or censoring date, whichever occurred first (maximum up to 43 months) | The ITT analysis set included all participants who were randomized on or before the date of LPI, in the global study. | Months | MEDIAN |
| SECONDARY | Overall Survival (OS) | Up to approximately 5 years | |||
| SECONDARY | Progression-Free Survival as Per RECIST v1.1 in Participants With Brain Metastases at Baseline Based on Investigator Assessment | From the date of randomization to the date of PD or death from any cause or censoring date, whichever occurred first (maximum up to 45 months) | The ITT analysis set included all participants who were randomized on or before the date of LPI, in the global study. Here Overall Number of Participants Analyzed signifies the number of participants evaluable for this outcome measure. | Months | MEDIAN |
| SECONDARY | Objective Response Rate (ORR) as Per RECIST v1.1 Based on Investigator Assessment | From the date of first CR or PR until the date of the first documentation of PD or death, whichever occurred first (maximum up to 43 months) | The ITT analysis set included all participants who were randomized on or before the date of LPI, in the global study. Here Overall Number of Participants Analyzed signifies the number of participants evaluable for this outcome measure. | Percentage of participants | NUMBER |
| SECONDARY | Overall Survival in Participants With Brain Metastases at Baseline | Up to approximately 5 years | |||
| SECONDARY | Progression-Free Survival as Per RECIST v1.1 Determined by Blinded Independent Committee Review (BICR) | From the date of randomization to the date of PD or death from any cause or censoring date, whichever occurred first (maximum up to 43 months) | The ITT analysis set included all participants who were randomized on or before the date of LPI, in the global study. | Months | MEDIAN |
| SECONDARY | Progression-Free Survival in Participants With Brain Metastases at Baseline as Per RECIST v1.1 Determined by BICR | From the date of randomization to the date of PD or death from any cause or censoring date, whichever occurred first (maximum up to 43 months) | The ITT analysis set included all participants who were randomized on or before the date of LPI, in the global study. Here Overall Number of Participants Analyzed signifies the number of participants evaluable for this outcome measure. | Months | MEDIAN |
| SECONDARY | Objective Response Rate as Per RECIST v1.1 Determined by BICR | From the date of randomization to the date of PD or death from any cause or censoring date, whichever occurred first (maximum up to 43 months) | The ITT analysis set included all participants who were randomized on or before the date of LPI, in the global study. Here Overall Number of Participants Analyzed signifies the number of participants evaluable for this outcome measure. | Percentage of participants | NUMBER |
| SECONDARY | Duration of Response (DOR) as Per RECIST v1.1 Based on Investigator Assessment | Up to approximately 5 years | |||
| SECONDARY | Duration of Response as Per RECIST v1.1 by BICR | Up to approximately 5 years |
1 to 10 of 13Source ClinicalTrials.gov
See all 13 outcomesResults by group14
Each measurement the trial posted, group by group, in the words and numbers it posted.
| Outcome | Group | Category | Value | Spread | Units |
|---|---|---|---|---|---|
| Progression-Free Survival (PFS) as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version (v)1.1 Based on Investigator Assessment | Tucatinib+ Ado-trastuzumab Emtansine | 9.5 | 95% Confidence Interval 7.4 to 10.9 | Months | |
| Progression-Free Survival (PFS) as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version (v)1.1 Based on Investigator Assessment | Placebo+ Ado-trastuzumab Emtansine | 7.4 | 95% Confidence Interval 5.6 to 8.1 | Months | |
| Progression-Free Survival as Per RECIST v1.1 in Participants With Brain Metastases at Baseline Based on Investigator Assessment | Tucatinib+ Ado-trastuzumab Emtansine | 7.8 | 95% Confidence Interval 6.7 to 10.0 | Months | |
| Progression-Free Survival as Per RECIST v1.1 in Participants With Brain Metastases at Baseline Based on Investigator Assessment | Placebo+ Ado-trastuzumab Emtansine | 5.7 | 95% Confidence Interval 4.6 to 7.5 | Months | |
| Objective Response Rate (ORR) as Per RECIST v1.1 Based on Investigator Assessment | Tucatinib+ Ado-trastuzumab Emtansine | 42.0 | 95% Confidence Interval 34.9 to 49.4 | Percentage of participants | |
| Objective Response Rate (ORR) as Per RECIST v1.1 Based on Investigator Assessment | Placebo+ Ado-trastuzumab Emtansine | 36.1 | 95% Confidence Interval 29.3 to 43.4 | Percentage of participants | |
| Progression-Free Survival as Per RECIST v1.1 Determined by Blinded Independent Committee Review (BICR) | Tucatinib+ Ado-trastuzumab Emtansine | 9.6 | 95% Confidence Interval 7.5 to 10.9 | Months | |
| Progression-Free Survival as Per RECIST v1.1 Determined by Blinded Independent Committee Review (BICR) | Placebo+ Ado-trastuzumab Emtansine | 7.4 | 95% Confidence Interval 5.5 to 8.4 | Months | |
| Progression-Free Survival in Participants With Brain Metastases at Baseline as Per RECIST v1.1 Determined by BICR | Tucatinib+ Ado-trastuzumab Emtansine | 7.8 | 95% Confidence Interval 6.9 to 10.0 | Months | |
| Progression-Free Survival in Participants With Brain Metastases at Baseline as Per RECIST v1.1 Determined by BICR | Placebo+ Ado-trastuzumab Emtansine | 5.5 | 95% Confidence Interval 4.2 to 7.4 | Months |
1 to 10 of 14Source ClinicalTrials.gov
See all 14 results by groupParticipant flow8
How many started, completed or left each group, period by period.
| Period | Milestone | Group | Participants | Units counted |
|---|---|---|---|---|
| Overall Study | STARTED | Tucatinib+ Ado-trastuzumab Emtansine | 231 | |
| Overall Study | STARTED | Placebo+ Ado-trastuzumab Emtansine | 235 | |
| Overall Study | Intent-to-Treat (ITT) Analysis Set | Tucatinib+ Ado-trastuzumab Emtansine | 228 | |
| Overall Study | Intent-to-Treat (ITT) Analysis Set | Placebo+ Ado-trastuzumab Emtansine | 235 | |
| Overall Study | COMPLETED | Tucatinib+ Ado-trastuzumab Emtansine | 151 | |
| Overall Study | COMPLETED | Placebo+ Ado-trastuzumab Emtansine | 159 | |
| Overall Study | NOT COMPLETED | Tucatinib+ Ado-trastuzumab Emtansine | 80 | |
| Overall Study | NOT COMPLETED | Placebo+ Ado-trastuzumab Emtansine | 76 |
Source ClinicalTrials.gov
Adverse events398
Each adverse event the trial posted, group by group: the participants affected out of those at risk.
| Type | Event | Organ system | Group | Affected | At risk | Events |
|---|---|---|---|---|---|---|
| other | Anaemia | Blood and lymphatic system disorders | Placebo+ Ado-trastuzumab Emtansine | 26 | 233 | 35 |
| other | Anaemia | Blood and lymphatic system disorders | Tucatinib+ Ado-trastuzumab Emtansine | 44 | 231 | 58 |
| other | Thrombocytopenia | Blood and lymphatic system disorders | Placebo+ Ado-trastuzumab Emtansine | 29 | 233 | 33 |
| other | Thrombocytopenia | Blood and lymphatic system disorders | Tucatinib+ Ado-trastuzumab Emtansine | 37 | 231 | 44 |
| other | Dry eye | Eye disorders | Placebo+ Ado-trastuzumab Emtansine | 14 | 233 | 14 |
| other | Dry eye | Eye disorders | Tucatinib+ Ado-trastuzumab Emtansine | 24 | 231 | 26 |
| other | Vision blurred | Eye disorders | Placebo+ Ado-trastuzumab Emtansine | 23 | 233 | 27 |
| other | Vision blurred | Eye disorders | Tucatinib+ Ado-trastuzumab Emtansine | 23 | 231 | 25 |
| other | Abdominal pain | Gastrointestinal disorders | Placebo+ Ado-trastuzumab Emtansine | 28 | 233 | 33 |
| other | Abdominal pain | Gastrointestinal disorders | Tucatinib+ Ado-trastuzumab Emtansine | 34 | 231 | 40 |
1 to 10 of 398Source ClinicalTrials.gov
See all 398 adverse eventsAdverse event totals6
The totals the trial posted for each group.
| Total | Group | Affected | At risk |
|---|---|---|---|
| Total, all-cause mortality | Placebo+ Ado-trastuzumab Emtansine | 63 | 233 |
| Total, all-cause mortality | Tucatinib+ Ado-trastuzumab Emtansine | 71 | 231 |
| Total, other adverse events | Placebo+ Ado-trastuzumab Emtansine | 227 | 233 |
| Total, other adverse events | Tucatinib+ Ado-trastuzumab Emtansine | 230 | 231 |
| Total, serious adverse events | Placebo+ Ado-trastuzumab Emtansine | 52 | 233 |
| Total, serious adverse events | Tucatinib+ Ado-trastuzumab Emtansine | 70 | 231 |
Source ClinicalTrials.gov
Papers1
The papers the trial lists on ClinicalTrials.gov.
| PMID | Listed as |
|---|---|
| 41260264 | DERIVED |
Source PubMed
Grants0
The grants NIH RePORTER links to the trial, newest funded first: NIH's, and some of AHRQ's, CDC's, FDA's and VA's. Each shows its title, principal investigators, organization and funder in its newest year.
None in this release.
Trial comparisons3
Comparisons of the trial's two groups, calculated by ConductScience from the counts it posted.
| Comparison | Source |
|---|---|
| Tucatinib+ Ado-trastuzumab Emtansine vs Placebo+ Ado-trastuzumab Emtansine: Number of Participants With Treatment Emergent Adverse Events (AEs) | Trial comparisons |
| Placebo+ Ado-trastuzumab Emtansine vs Tucatinib+ Ado-trastuzumab Emtansine: deaths from any cause | Trial comparisons |
| Placebo+ Ado-trastuzumab Emtansine vs Tucatinib+ Ado-trastuzumab Emtansine: serious adverse events | Trial comparisons |
Tests0
The ConductCognition tests this trial's registered outcomes name, as ScienceGraph matched them in trial-tests-2026-11-12-0.2.1.
None in this release.
Data dates
The day each source was copied for this release.
Sources 3
- ClinicalTrials.gov's posted results, through CTTI's AACTFreely available. Acknowledgement requested
- ClinicalTrials.govNo license stated
- NIH RePORTER's clinical studies and project filesPublic domain
Each source's terms
- ClinicalTrials.gov's posted results, through CTTI's AACTClinicalTrials.gov data via Aggregate Analysis of ClinicalTrials.gov (AACT), CTTI. CTTI makes its materials freely available and requests acknowledgement. https://aact.ctti-clinicaltrials.org/documentation/299
- ClinicalTrials.govnone stated
- NIH RePORTER's clinical studies and project filesPublic domain (NIH RePORTER)
ClinicalTrials.gov's data carry an international copyright outside the United States: https://clinicaltrials.gov/about-site/terms-conditions.
For software
Read this trial from software.
The record and each of its lists are JSON, twenty rows a page. No key.
GET https://conductscience.org/api/trials/v1/NCT03975647
GET https://conductscience.org/api/trials/v1/NCT03975647/events?page=2