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, Japan
for more information at clinicaltrials.gov
EXPERIMENTAL: Cohort 1A
Tucatinib + trastuzumab + FOLFOX given in 14-day cycles
DRUG: tucatinib
For Cohort 1A, 150 mg will be administered twice daily by mouth (orally) from Cycle 1 Day 8 onwards. For all other cohorts, 300 mg (or intermediate dose) will be given orally twice daily starting on Cycle 1 Day 1.DRUG: trastuzumab
Cohorts 1A and 1B: a 6 mg/kg loading dose will be given into the vein (IV; intravenously) on Cycle 1 Day 1, followed by a dose of 4 mg/kg IV every 2 weeks starting on Cycle 2 Day 1. Cohorts 1C, 1D, 1E, 1F, 1G, 2A, and 2B: an 8 mg/kg loading dose will be administered IV on Cycle 1 Day 1, followed by a dose of 6 mg/kg IV every 3 weeks thereafter.DRUG: oxaliplatin
85 mg/m\^2 given IV every 2 weeks for cohorts using FOLFOX. For cohorts using CAPOX regimen, 130 mg/m\^2 given every 3 weeks.DRUG: leucovorin
200 (mFOLFOX7) or 400 (mFOLFOX6) mg/m\^2 given IV every 2 weeks. Part of FOLFOX regimen.DRUG: fluorouracil
400 mg/m\^2 (IV bolus after leucovorin) and/or 2400 mg/m\^2 (continuous infusion over 46 hours). Part of FOLFOX regimen.EXPERIMENTAL: Cohort 1B
Tucatinib + trastuzumab + FOLFOX given in 14-day cycles
DRUG: tucatinib
For Cohort 1A, 150 mg will be administered twice daily by mouth (orally) from Cycle 1 Day 8 onwards. For all other cohorts, 300 mg (or intermediate dose) will be given orally twice daily starting on Cycle 1 Day 1.DRUG: trastuzumab
Cohorts 1A and 1B: a 6 mg/kg loading dose will be given into the vein (IV; intravenously) on Cycle 1 Day 1, followed by a dose of 4 mg/kg IV every 2 weeks starting on Cycle 2 Day 1. Cohorts 1C, 1D, 1E, 1F, 1G, 2A, and 2B: an 8 mg/kg loading dose will be administered IV on Cycle 1 Day 1, followed by a dose of 6 mg/kg IV every 3 weeks thereafter.DRUG: oxaliplatin
85 mg/m\^2 given IV every 2 weeks for cohorts using FOLFOX. For cohorts using CAPOX regimen, 130 mg/m\^2 given every 3 weeks.DRUG: leucovorin
200 (mFOLFOX7) or 400 (mFOLFOX6) mg/m\^2 given IV every 2 weeks. Part of FOLFOX regimen.DRUG: fluorouracil
400 mg/m\^2 (IV bolus after leucovorin) and/or 2400 mg/m\^2 (continuous infusion over 46 hours). Part of FOLFOX regimen.EXPERIMENTAL: Cohort 1C
Tucatinib + trastuzumab + CAPOX given in 21-day cycles
DRUG: tucatinib
For Cohort 1A, 150 mg will be administered twice daily by mouth (orally) from Cycle 1 Day 8 onwards. For all other cohorts, 300 mg (or intermediate dose) will be given orally twice daily starting on Cycle 1 Day 1.DRUG: trastuzumab
Cohorts 1A and 1B: a 6 mg/kg loading dose will be given into the vein (IV; intravenously) on Cycle 1 Day 1, followed by a dose of 4 mg/kg IV every 2 weeks starting on Cycle 2 Day 1. Cohorts 1C, 1D, 1E, 1F, 1G, 2A, and 2B: an 8 mg/kg loading dose will be administered IV on Cycle 1 Day 1, followed by a dose of 6 mg/kg IV every 3 weeks thereafter.DRUG: oxaliplatin
85 mg/m\^2 given IV every 2 weeks for cohorts using FOLFOX. For cohorts using CAPOX regimen, 130 mg/m\^2 given every 3 weeks.DRUG: capecitabine
1000 mg/m\^2 is taken twice per day orally on Days 1-14 of each 3 week cycle. Part of CAPOX regimen.EXPERIMENTAL: Cohort 1D
Tucatinib + trastuzumab + FOLFOX. Tucatinib and FOLFOX given in 14-day cycles and trastuzumab given every 21 days
DRUG: tucatinib
For Cohort 1A, 150 mg will be administered twice daily by mouth (orally) from Cycle 1 Day 8 onwards. For all other cohorts, 300 mg (or intermediate dose) will be given orally twice daily starting on Cycle 1 Day 1.DRUG: trastuzumab
Cohorts 1A and 1B: a 6 mg/kg loading dose will be given into the vein (IV; intravenously) on Cycle 1 Day 1, followed by a dose of 4 mg/kg IV every 2 weeks starting on Cycle 2 Day 1. Cohorts 1C, 1D, 1E, 1F, 1G, 2A, and 2B: an 8 mg/kg loading dose will be administered IV on Cycle 1 Day 1, followed by a dose of 6 mg/kg IV every 3 weeks thereafter.DRUG: oxaliplatin
85 mg/m\^2 given IV every 2 weeks for cohorts using FOLFOX. For cohorts using CAPOX regimen, 130 mg/m\^2 given every 3 weeks.DRUG: leucovorin
200 (mFOLFOX7) or 400 (mFOLFOX6) mg/m\^2 given IV every 2 weeks. Part of FOLFOX regimen.DRUG: fluorouracil
400 mg/m\^2 (IV bolus after leucovorin) and/or 2400 mg/m\^2 (continuous infusion over 46 hours). Part of FOLFOX regimen.EXPERIMENTAL: Cohort 1E
Tucatinib + trastuzumab + pembrolizumab + FOLFOX. Tucatinib and FOLFOX given in 14-day cycles, trastuzumab given in 21-day cycles, and pembrolizumab given in 42-day cycles
DRUG: tucatinib
For Cohort 1A, 150 mg will be administered twice daily by mouth (orally) from Cycle 1 Day 8 onwards. For all other cohorts, 300 mg (or intermediate dose) will be given orally twice daily starting on Cycle 1 Day 1.DRUG: trastuzumab
Cohorts 1A and 1B: a 6 mg/kg loading dose will be given into the vein (IV; intravenously) on Cycle 1 Day 1, followed by a dose of 4 mg/kg IV every 2 weeks starting on Cycle 2 Day 1. Cohorts 1C, 1D, 1E, 1F, 1G, 2A, and 2B: an 8 mg/kg loading dose will be administered IV on Cycle 1 Day 1, followed by a dose of 6 mg/kg IV every 3 weeks thereafter.DRUG: oxaliplatin
85 mg/m\^2 given IV every 2 weeks for cohorts using FOLFOX. For cohorts using CAPOX regimen, 130 mg/m\^2 given every 3 weeks.DRUG: leucovorin
200 (mFOLFOX7) or 400 (mFOLFOX6) mg/m\^2 given IV every 2 weeks. Part of FOLFOX regimen.DRUG: fluorouracil
400 mg/m\^2 (IV bolus after leucovorin) and/or 2400 mg/m\^2 (continuous infusion over 46 hours). Part of FOLFOX regimen.DRUG: pembrolizumab
400 mg given by IV on day 1 of cycle 1, then every 6 weeks.EXPERIMENTAL: Cohort 1F
Tucatinib + trastuzumab + pembrolizumab + CAPOX. Tucatinib, trastuzumab, and CAPOX given in 21-day cycles and pembrolizumab given in 42-day cycles.
DRUG: tucatinib
For Cohort 1A, 150 mg will be administered twice daily by mouth (orally) from Cycle 1 Day 8 onwards. For all other cohorts, 300 mg (or intermediate dose) will be given orally twice daily starting on Cycle 1 Day 1.DRUG: trastuzumab
Cohorts 1A and 1B: a 6 mg/kg loading dose will be given into the vein (IV; intravenously) on Cycle 1 Day 1, followed by a dose of 4 mg/kg IV every 2 weeks starting on Cycle 2 Day 1. Cohorts 1C, 1D, 1E, 1F, 1G, 2A, and 2B: an 8 mg/kg loading dose will be administered IV on Cycle 1 Day 1, followed by a dose of 6 mg/kg IV every 3 weeks thereafter.DRUG: oxaliplatin
85 mg/m\^2 given IV every 2 weeks for cohorts using FOLFOX. For cohorts using CAPOX regimen, 130 mg/m\^2 given every 3 weeks.DRUG: capecitabine
1000 mg/m\^2 is taken twice per day orally on Days 1-14 of each 3 week cycle. Part of CAPOX regimen.DRUG: pembrolizumab
400 mg given by IV on day 1 of cycle 1, then every 6 weeks.EXPERIMENTAL: Cohort 1G
Tucatinib + trastuzumab + pembrolizumab. Tucatinib and trastuzumab given in 21-day cycles and pembrolizumab given in 42-day cycles.
DRUG: tucatinib
For Cohort 1A, 150 mg will be administered twice daily by mouth (orally) from Cycle 1 Day 8 onwards. For all other cohorts, 300 mg (or intermediate dose) will be given orally twice daily starting on Cycle 1 Day 1.DRUG: trastuzumab
Cohorts 1A and 1B: a 6 mg/kg loading dose will be given into the vein (IV; intravenously) on Cycle 1 Day 1, followed by a dose of 4 mg/kg IV every 2 weeks starting on Cycle 2 Day 1. Cohorts 1C, 1D, 1E, 1F, 1G, 2A, and 2B: an 8 mg/kg loading dose will be administered IV on Cycle 1 Day 1, followed by a dose of 6 mg/kg IV every 3 weeks thereafter.DRUG: pembrolizumab
400 mg given by IV on day 1 of cycle 1, then every 6 weeks.EXPERIMENTAL: Cohort 2A
Tucatinib + trastuzumab + pembrolizumab + (FOLFOX or CAPOX). Either (1) tucatinib and FOLFOX given in 14-day cycles or (2) tucatinib and CAPOX given in 21-day cycles. Trastuzumab given in 21-day cycles and pembrolizumab given in 42-day cycles.
DRUG: tucatinib
For Cohort 1A, 150 mg will be administered twice daily by mouth (orally) from Cycle 1 Day 8 onwards. For all other cohorts, 300 mg (or intermediate dose) will be given orally twice daily starting on Cycle 1 Day 1.DRUG: trastuzumab
Cohorts 1A and 1B: a 6 mg/kg loading dose will be given into the vein (IV; intravenously) on Cycle 1 Day 1, followed by a dose of 4 mg/kg IV every 2 weeks starting on Cycle 2 Day 1. Cohorts 1C, 1D, 1E, 1F, 1G, 2A, and 2B: an 8 mg/kg loading dose will be administered IV on Cycle 1 Day 1, followed by a dose of 6 mg/kg IV every 3 weeks thereafter.DRUG: oxaliplatin
85 mg/m\^2 given IV every 2 weeks for cohorts using FOLFOX. For cohorts using CAPOX regimen, 130 mg/m\^2 given every 3 weeks.DRUG: leucovorin
200 (mFOLFOX7) or 400 (mFOLFOX6) mg/m\^2 given IV every 2 weeks. Part of FOLFOX regimen.DRUG: fluorouracil
400 mg/m\^2 (IV bolus after leucovorin) and/or 2400 mg/m\^2 (continuous infusion over 46 hours). Part of FOLFOX regimen.DRUG: capecitabine
1000 mg/m\^2 is taken twice per day orally on Days 1-14 of each 3 week cycle. Part of CAPOX regimen.DRUG: pembrolizumab
400 mg given by IV on day 1 of cycle 1, then every 6 weeks.EXPERIMENTAL: Cohort 2B
Tucatinib + trastuzumab + FOLFOX given in 14-day cycles.
DRUG: tucatinib
For Cohort 1A, 150 mg will be administered twice daily by mouth (orally) from Cycle 1 Day 8 onwards. For all other cohorts, 300 mg (or intermediate dose) will be given orally twice daily starting on Cycle 1 Day 1.DRUG: trastuzumab
Cohorts 1A and 1B: a 6 mg/kg loading dose will be given into the vein (IV; intravenously) on Cycle 1 Day 1, followed by a dose of 4 mg/kg IV every 2 weeks starting on Cycle 2 Day 1. Cohorts 1C, 1D, 1E, 1F, 1G, 2A, and 2B: an 8 mg/kg loading dose will be administered IV on Cycle 1 Day 1, followed by a dose of 6 mg/kg IV every 3 weeks thereafter.DRUG: oxaliplatin
85 mg/m\^2 given IV every 2 weeks for cohorts using FOLFOX. For cohorts using CAPOX regimen, 130 mg/m\^2 given every 3 weeks.DRUG: leucovorin
200 (mFOLFOX7) or 400 (mFOLFOX6) mg/m\^2 given IV every 2 weeks. Part of FOLFOX regimen.DRUG: fluorouracil
400 mg/m\^2 (IV bolus after leucovorin) and/or 2400 mg/m\^2 (continuous infusion over 46 hours). Part of FOLFOX regimen.Incidence of renal dose-limiting toxicities (DLTs) (Cohorts 1A and 1B)
Up to one month; 2 cycles after receiving all study treatment (each cycle is 14 days)
Incidence of adverse events (AEs) (Cohorts 1C, 1D, 1E, 1F, 1G, 2A, and 2B)
An AE is defined as any untoward medical occurrence in a clinical investigational participant administered a medicinal product and which does not necessarily have a causal relationship with this treatment.
Up to approximately 12 months
Incidence of laboratory abnormalities (Cohorts 1C, 1D, 1E, 1F, 1G, 2A, and 2B)
Up to approximately 12 months
Incidence of DLTs (Cohorts 1C, 1D, 1E, 1F, and 1G)
Up to approximately 12 months
Incidence of dose alterations (Cohort 1D)
Up to approximately 12 months
Incidence of AEs (Cohorts 1A and 1B)
An AE is defined as any untoward medical occurrence in a clinical investigational participant administered a medicinal product and which does not necessarily have a causal relationship with this treatment.
Up to approximately 12 months
Incidence of laboratory abnormalities (Cohorts 1A and 1B)
Up to approximately 12 months
Change in glomerular filtration rate (GFR) from baseline through 2 cycles of combination therapy (Cohorts 1A and 1B)
To be summarized using descriptive statistics
Up to approximately 6 weeks
Pharmacokinetic (PK) parameter of tucatinib - AUClast (Cohorts 1A and 1B)
To be summarized using descriptive statistics
Up to approximately 2.5 months; through predose of Cycle 2, Day 1 (each cycle is 14 days)
PK parameter of tucatinib - Cmax (Cohorts 1A and 1B)
To be summarized using descriptive statistics
Up to approximately 2.5 months; through predose of Cycle 2, Day 1 (each cycle is 14 days)
PK parameter of tucatinib - Ctrough (Cohorts 1A, 1B, 1C, 1E, 1F, and 1G)
To be summarized using descriptive statistics
Up to approximately 2.5 months; through predose of Cycle 6, Day 1
PK parameter of tucatinib - Tmax (Cohorts 1A and 1B)
To be summarized using descriptive statistics
Up to approximately 2.5 months; through predose of Cycle 2, Day 1 (each cycle is 14 days)
PK parameter of oxaliplatin - AUClast (Cohorts 1A and 1B)
To be summarized using descriptive statistics
Up to 15 days; through Cycle 2, Day 1 (each cycle is 14 days)
PK parameter of oxaliplatin - Cmax (Cohorts 1A and 1B)
To be summarized using descriptive statistics
Up to 15 days; through Cycle 2, Day 1 (each cycle is 14 days)
PK parameter of oxaliplatin - Tmax (Cohorts 1A and 1B)
To be summarized using descriptive statistics
Up to 15 days; through Cycle 2, Day 1 (each cycle is 14 days)
Confirmed objective response rate (cORR) according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 per investigator assessment (INV) (Cohort 2A)
cORR is defined as the proportion of participants with confirmed complete response (CR) or partial response (PR)
Up to approximately 2.5 years
Duration of response (DOR) according to RECIST v1.1 per INV (Cohorts 1C, 1E, 1F, 1G, and 2A)
DOR is defined as the time from first documentation of objective response of confirmed CR or confirmed PR to the first documentation of disease progression or death from any cause, whichever occurs first.
Up to approximately 2.5 years
Progression-free survival (PFS) according to RECIST v1.1 per INV (Cohorts 1C, 1E, 1F, 1G, and 2A)
PFS is defined as the time from the date of treatment initiation to the date of disease progression or death from any cause, which occurs first.
Up to approximately 2.5 years
Overall survival (OS) (Cohort 1C, 1E, 1F, 1G, and 2A)
OS is defined as the time from treatment initiation to death due to any cause
Up to approximately 2.5 years
Objective response rate (ORR) (Cohorts 1C, 1E, 1F, and 1G)
ORR is defined as the proportion of subjects with confirmed CR or PR, according to RECIST v1.1.
Up to approximately 2.5 years
40
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.
NCT04430738
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