The safety and efficacy of this agent(s), or use in this setting, has not been established or is subject to confirmation. For an agent(s) whose safety and efficacy has not been established or confirmed, future regulatory approval or commercial availability is not guaranteed.
Active Not-enrolling
United States, Australia, Austria, Belgium, Canada, China, Denmark, France, Germany, Israel, Italy, Japan, Korea, Republic of, Netherlands, Singapore, Spain, Sweden, Switzerland, Taiwan, United Kingdom
EXPERIMENTAL: Tucatinib + T-DM1
Tucatinib + T-DM1
DRUG: tucatinib
300mg given twice per day by mouth (orally)
DRUG: T-DM1
3.6 mg/kg given into the vein (IV; intravenously) every 21 days
ACTIVE_COMPARATOR: Placebo + T-DM1
Placebo + T-DM1
DRUG: placebo
Given twice per day orally
DRUG: T-DM1
3.6 mg/kg given into the vein (IV; intravenously) every 21 days
CNS Inclusion - Based on screening contrast brain magnetic resonance imaging (MRI), participants 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
Participants 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 14 days prior to first dose, or time since surgical resection is at least 28 days.
(ii) Other sites of evaluable disease are present
Progression-free survival (PFS) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 by investigator assessment
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.
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)
Overall Survival
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).
Up to approximately 5 years
Progression-Free Survival as Per RECIST v1.1 in Participants With Brain Metastases at Baseline Based on Investigator Assessment
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.
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)
Objective Response Rate (ORR) as Per RECIST v1.1 Based on Investigator Assessment
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.
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)
Overall Survival in Participants With Brain Metastases at Baseline
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.
Up to approximately 5 years
Progression-Free Survival as Per RECIST v1.1 Determined by Blinded Independent Committee Review (BICR)
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.
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)
Progression-Free Survival in Participants With Brain Metastases at Baseline as Per RECIST v1.1 Determined by BICR
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.
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)
Objective Response Rate as Per RECIST v1.1 Determined by BICR
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.
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)
Duration of Response (DOR) as Per RECIST v1.1 Based on Investigator Assessment
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.
Up to approximately 5 years
Duration of Response as Per RECIST v1.1 by BICR
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.
Up to approximately 5 years
Clinical Benefit Rate (CBR) Per RECIST v1.1 Based on Investigator Assessment
CBR was defined as the percentage of participants with stable disease (SD) or non-CR or non-PD >= 6 months or best response of CR or PR according to RECIST v1.1. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. 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. CBR was based on investigator assessment.
Up to approximately 3 years
Clinical Benefit Rate as Per RECIST v1.1 by BICR
CBR was defined as the percentage of participants with SD or non-CR or non-PD >= 6 months or best response of CR or PR according to RECIST v1.1. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. 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. CBR per BICR is based on BICR response assessments.
Up to approximately 3 years
Number of Participants With Treatment Emergent Adverse Events (AEs)
An AE was any untoward medical occurrence in a participant or clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. TEAE was defined as AE that is newly occurred or worsened after the start of study treatment.
From start of treatment up to 30 days after the last study treatment (approximately 43 months)
466
Sponsor: Seagen Inc.
Collaborator: None
For more information, call or email the Pfizer Clinical Trial Contact Center:
When calling, please reference this study number:
NCT# stands for National Clinical Trial number. This is a unique identification code given to each clinical trial registered on ClinicalTrials.gov. The format is "NCT" followed by an 8-digit number (for example, NCT00000419). Also called the ClinicalTrials.gov identifier.
NCT03975647
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