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Tucatinib Plus Trastuzumab in Patients With HER2+ Colorectal 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. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03043313
Recruitment Status : Completed
First Posted : February 6, 2017
Results First Posted : April 18, 2023
Last Update Posted : November 13, 2023
Sponsor:
Collaborators:
National Cancer Institute (NCI)
Academic and Community Cancer Research United
Information provided by (Responsible Party):
Seagen Inc.

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Metastatic Colorectal Adenocarcinoma
Interventions Drug: Trastuzumab
Drug: Tucatinib
Enrollment 117
Recruitment Details A total of 117 participants were enrolled at a total of 56 sites in the United States, Italy, France, Belgium, and Spain. The date of first participant enrollment was 23-Jun-2017. The date of last participant randomization was 22-Sep-2021.
Pre-assignment Details  
Arm/Group Title Tucatinib+Trastuzumab (Cohort A) Tucatinib+Trastuzumab (Cohort B) Tucatinib Monotherapy (Cohort C)
Hide Arm/Group Description Non-randomized cohort. Tucatinib 300 mg PO BID on Days 1 to 21 of each 21-day cycle. Trastuzumab 8 mg/kg by IV infusion on Day 1 of Cycle 1 and 6 mg/kg on Day 1 of each subsequent cycle. Randomized cohort. Tucatinib 300 mg PO BID on Days 1 to 21 of each 21-day cycle. Trastuzumab 8 mg/kg by IV infusion on Day 1 of Cycle 1 and 6 mg/kg on Day 1 of each subsequent cycle. Randomized cohort. Tucatinib 300 mg PO BID on Days 1 to 21 of each 21-day cycle. Participants who do not respond to therapy may have the option to receive tucatinib and trastuzumab.
Period Title: Overall Study
Started 45 41 31
Completed 0 0 0
Not Completed 45 41 31
Reason Not Completed
Withdrawal by Subject             4             1             1
Lost to Follow-up             1             0             0
Death             26             13             8
On Treatment             7             12             11
In follow up             7             15             11
Arm/Group Title Tucatinib+Trastuzumab (Cohort A) Tucatinib+Trastuzumab (Cohort B) Tucatinib Monotherapy (Cohort C) Total
Hide Arm/Group Description Non-randomized cohort. Tucatinib 300 mg PO BID on Days 1 to 21 of each 21-day cycle. Trastuzumab 8 mg/kg by IV infusion on Day 1 of Cycle 1 and 6 mg/kg on Day 1 of each subsequent cycle. Randomized cohort. Tucatinib 300 mg PO BID on Days 1 to 21 of each 21-day cycle. Trastuzumab 8 mg/kg by IV infusion on Day 1 of Cycle 1 and 6 mg/kg on Day 1 of each subsequent cycle. Randomized cohort. Tucatinib 300 mg PO BID on Days 1 to 21 of each 21-day cycle. Participants who do not respond to therapy may have the option to receive tucatinib and trastuzumab. Total of all reporting groups
Overall Number of Baseline Participants 45 39 30 114
Hide Baseline Analysis Population Description
The Full Analysis Set includes all subjects who were enrolled and received any amount of study treatment and had HER2+ tumors as defined by one or more protocol required local tests.
Age, Continuous  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 45 participants 39 participants 30 participants 114 participants
52
(24 to 71)
57
(31 to 77)
59.5
(29 to 75)
56
(24 to 77)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 45 participants 39 participants 30 participants 114 participants
Female
19
  42.2%
14
  35.9%
15
  50.0%
48
  42.1%
Male
26
  57.8%
25
  64.1%
15
  50.0%
66
  57.9%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 45 participants 39 participants 30 participants 114 participants
Hispanic or Latino
2
   4.4%
1
   2.6%
1
   3.3%
4
   3.5%
Not Hispanic or Latino
35
  77.8%
29
  74.4%
25
  83.3%
89
  78.1%
Unknown or Not Reported
8
  17.8%
9
  23.1%
4
  13.3%
21
  18.4%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 45 participants 39 participants 30 participants 114 participants
American Indian or Alaska Native
1
   2.2%
0
   0.0%
0
   0.0%
1
   0.9%
Asian
2
   4.4%
1
   2.6%
0
   0.0%
3
   2.6%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
1
   2.2%
2
   5.1%
3
  10.0%
6
   5.3%
White
37
  82.2%
28
  71.8%
23
  76.7%
88
  77.2%
More than one race
1
   2.2%
0
   0.0%
0
   0.0%
1
   0.9%
Unknown or Not Reported
3
   6.7%
8
  20.5%
4
  13.3%
15
  13.2%
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
 Number Analyzed 45 participants 39 participants 30 participants 114 participants
North America
45
 100.0%
24
  61.5%
16
  53.3%
85
  74.6%
Europe
0
   0.0%
15
  38.5%
14
  46.7%
29
  25.4%
Eastern Cooperative Oncology Group (ECOG) Performance Status   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 45 participants 39 participants 30 participants 114 participants
Grade 0
24
  53.3%
26
  66.7%
17
  56.7%
67
  58.8%
Grade 1
20
  44.4%
11
  28.2%
13
  43.3%
44
  38.6%
Grade 2
1
   2.2%
2
   5.1%
0
   0.0%
3
   2.6%
[1]
Measure Description: Measure Description: 0=Normal activity; 1=Symptoms but ambulatory; 2=In bed <50% of the time; 3= In bed >50% of the time; 4=100% bedridden; 5=Dead
1.Primary Outcome
Title Confirmed Objective Response Rate (cORR) Per RECIST 1.1 Per Blinded Independent Central Review (BICR) in Pooled Cohorts A+B
Hide Description cORR is defined as the percentage of participants with confirmed complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1).
Time Frame Up to 46.6 months
Hide Outcome Measure Data
Hide Analysis Population Description
The Full Analysis Set includes all subjects who were enrolled and received any amount of study treatment and had HER2+ tumors as defined by one or more protocol required local tests.
Arm/Group Title Tucatinib+Trastuzumab (Cohorts A+B)
Hide Arm/Group Description:
Tucatinib 300 mg PO BID on Days 1 to 21 of each 21-day cycle. Trastuzumab 8 mg/kg by IV infusion on Day 1 of Cycle 1 and 6 mg/kg on Day 1 of each subsequent cycle.
Overall Number of Participants Analyzed 84
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of Participants
38.1
(27.7 to 49.3)
2.Secondary Outcome
Title ORR by 12 Weeks of Treatment Per RECIST 1.1 According to BICR Assessment
Hide Description ORR per BICR by 12 Weeks is defined as the percentage of participants with CR or PR by 12 weeks of treatment, and before time of crossover (Cohort C), whichever comes earlier.
Time Frame Up to 3 months
Hide Outcome Measure Data
Hide Analysis Population Description
The Full Analysis Set includes all subjects who were enrolled and received any amount of study treatment and had HER2+ tumors as defined by one or more protocol required local tests.
Arm/Group Title Tucatinib+Trastuzumab (Cohorts A+B) Tucatinib Monotherapy (Cohort C)
Hide Arm/Group Description:
Tucatinib 300 mg PO BID on Days 1 to 21 of each 21-day cycle. Trastuzumab 8 mg/kg by IV infusion on Day 1 of Cycle 1 and 6 mg/kg on Day 1 of each subsequent cycle.
Randomized cohort. Tucatinib 300 mg PO BID on Days 1 to 21 of each 21-day cycle. Participants who do not respond to therapy may have the option to receive tucatinib and trastuzumab.
Overall Number of Participants Analyzed 84 30
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of Participants
28.6
(19.2 to 39.5)
3.3
(0.1 to 17.2)
3.Secondary Outcome
Title Duration of Response (DOR) Per RECIST 1.1 According to BICR Assessment
Hide Description DOR is defined as the time from the first objective response (CR or PR that is subsequently confirmed) to documented PD per RECIST 1.1 or death from any cause, whichever occurs first.
Time Frame Up to 44.7 months
Hide Outcome Measure Data
Hide Analysis Population Description
The Full Analysis Set includes all subjects who were enrolled and received any amount of study treatment and had HER2+ tumors as defined by one or more protocol required local tests.
Arm/Group Title Tucatinib+Trastuzumab (Cohorts A+B) Tucatinib Monotherapy (Cohort C)
Hide Arm/Group Description:
Tucatinib 300 mg PO BID on Days 1 to 21 of each 21-day cycle. Trastuzumab 8 mg/kg by IV infusion on Day 1 of Cycle 1 and 6 mg/kg on Day 1 of each subsequent cycle.
Randomized cohort. Tucatinib 300 mg PO BID on Days 1 to 21 of each 21-day cycle. Participants who do not respond to therapy may have the option to receive tucatinib and trastuzumab.
Overall Number of Participants Analyzed 84 30
Median (95% Confidence Interval)
Unit of Measure: Months
12.4
(8.5 to 20.5)
NA [1] 
(NA to NA)
[1]
Not enough events in Cohort C to calculate Median or Lower and Upper Limits.
4.Secondary Outcome
Title Progression-Free Survival (PFS) Per RECIST 1.1 According to BICR Assessment for Pooled Cohorts A+B
Hide Description PFS is defined as the time from start of study treatment (Cohort A) or date of randomization (Cohort B) to documented disease progression (as determined by BICR per RECIST 1.1) or death from any cause, whichever occurs first.
Time Frame Up to 46.6 months
Hide Outcome Measure Data
Hide Analysis Population Description
The Full Analysis Set includes all subjects who were enrolled and received any amount of study treatment and had HER2+ tumors as defined by one or more protocol required local tests.
Arm/Group Title Tucatinib+Trastuzumab (Cohorts A+B)
Hide Arm/Group Description:
Tucatinib 300 mg PO BID on Days 1 to 21 of each 21-day cycle. Trastuzumab 8 mg/kg by IV infusion on Day 1 of Cycle 1 and 6 mg/kg on Day 1 of each subsequent cycle.
Overall Number of Participants Analyzed 84
Median (95% Confidence Interval)
Unit of Measure: Months
8.2
(4.2 to 10.3)
5.Secondary Outcome
Title Overall Survival (OS) in Pooled Cohorts A+B
Hide Description OS is defined as the time from start of study treatment (Cohort A) or randomization (Cohort B) to date of death due to any cause.
Time Frame Up to 53 months
Hide Outcome Measure Data
Hide Analysis Population Description
The Full Analysis Set includes all subjects who were enrolled and received any amount of study treatment and had HER2+ tumors as defined by one or more protocol required local tests.
Arm/Group Title Tucatinib+Trastuzumab (Cohorts A+B)
Hide Arm/Group Description:
Tucatinib 300 mg PO BID on Days 1 to 21 of each 21-day cycle. Trastuzumab 8 mg/kg by IV infusion on Day 1 of Cycle 1 and 6 mg/kg on Day 1 of each subsequent cycle.
Overall Number of Participants Analyzed 84
Median (95% Confidence Interval)
Unit of Measure: Months
24.1
(20.3 to 36.7)
6.Secondary Outcome
Title Number of Participants With Adverse Events (AEs)
Hide Description An AE is any untoward medical occurrence in a patient or clinical investigational participant administered a medicinal product and which does not necessarily have a causal relationship with this treatment. Treatment emergent AEs (TEAEs) are defined as events that are new or worsened on or after receiving the first dose of study treatment (tucatinib or trastuzumab) and up through 30 days after the last dose of study treatment (tucatinib or trastuzumab).
Time Frame Up to 49.3 months
Hide Outcome Measure Data
Hide Analysis Population Description
The safety analysis set includes subjects who received any amount of study treatment.
Arm/Group Title Tucatinib+Trastuzumab (Cohorts A+B) Tucatinib Monotherapy (Cohort C)
Hide Arm/Group Description:
Tucatinib 300 mg PO BID on Days 1 to 21 of each 21-day cycle. Trastuzumab 8 mg/kg by IV infusion on Day 1 of Cycle 1 and 6 mg/kg on Day 1 of each subsequent cycle.
Randomized cohort. Tucatinib 300 mg PO BID on Days 1 to 21 of each 21-day cycle. Participants who do not respond to therapy may have the option to receive tucatinib and trastuzumab.
Overall Number of Participants Analyzed 86 30
Measure Type: Count of Participants
Unit of Measure: Participants
Any TEAE
82
  95.3%
28
  93.3%
Tucatinib-related TEAE
63
  73.3%
22
  73.3%
Trastuzumab-related TEAE
58
  67.4%
 NA [1] 
Any grade 3-5 TEAE
33
  38.4%
8
  26.7%
Tucatinib-related grade 3-5 TEAE
8
   9.3%
2
   6.7%
Trastuzumab-related grade 3-5 TEAE
6
   7.0%
 NA [1] 
Any Treatment-Emergent Serious AE (TESAE)
19
  22.1%
3
  10.0%
Tucatinib-related TESAE
3
   3.5%
1
   3.3%
Trastuzumab-related TESAE
2
   2.3%
 NA [1] 
TEAE leading to death
0
   0.0%
0
   0.0%
Discontinuation of any study treatment due to TEAE
5
   5.8%
0
   0.0%
Discontinuation of tucatinib due to TEAE
5
   5.8%
0
   0.0%
Discontinuation of tucatinib due to tucatinib-related TEAE
2
   2.3%
0
   0.0%
Discontinuation of trastuzumab due to TEAE
3
   3.5%
 NA [1] 
Discontinuation of trastuzumab due to trastuzumab-related TEAE
0
   0.0%
 NA [1] 
[1]
Tucatinib monotherapy arm
7.Secondary Outcome
Title Number of Participants With AEs Resulting in Dose Modification
Hide Description Dose modification included dose reduction and dose withheld by investigator due to AEs. Dose holds were defined as any instances where planned administration of the study drug was temporarily withheld or interrupted at the direction of the treating physician. Dose reductions of trastuzumab were not allowed; if trastuzumab could not be restarted after being held for a TEAE, it was discontinued.
Time Frame Up to 49.3 months
Hide Outcome Measure Data
Hide Analysis Population Description
The safety analysis set includes subjects who received any amount of study treatment.
Arm/Group Title Tucatinib+Trastuzumab (Cohorts A+B) Tucatinib Monotherapy (Cohort C)
Hide Arm/Group Description:
Tucatinib 300 mg PO BID on Days 1 to 21 of each 21-day cycle. Trastuzumab 8 mg/kg by IV infusion on Day 1 of Cycle 1 and 6 mg/kg on Day 1 of each subsequent cycle.
Randomized cohort. Tucatinib 300 mg PO BID on Days 1 to 21 of each 21-day cycle. Participants who do not respond to therapy may have the option to receive tucatinib and trastuzumab.
Overall Number of Participants Analyzed 86 30
Measure Type: Count of Participants
Unit of Measure: Participants
Tucatinib dose held
20
  23.3%
3
  10.0%
Tucatinib dose reduced
8
   9.3%
1
   3.3%
Trastuzumab dose held
24
  27.9%
 NA [1] 
Trastuzumab infusion interrupted (received full dose within 24 hrs)
6
   7.0%
 NA [1] 
Trastuzumab infusion stopped early (full dose not received)
1
   1.2%
 NA [1] 
[1]
Tucatinib monotherapy arm
8.Secondary Outcome
Title Number of Participants With Treatment-Emergent Laboratory Abnormalities (Hematology)
Hide Description Treatment emergent laboratory abnormalities are defined as abnormalities that are new or worsened on or after receiving the first dose of study treatment and up through 30 days after the last dose of study treatment. NCI CTCAE v5.0 is used for creatinine increased. NCI CTCAE v4.03 is used for the other lab parameters.
Time Frame Up to 49.3 months
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in the safety analysis set with both baseline and post-baseline results for each test.
Arm/Group Title Tucatinib+Trastuzumab (Cohorts A+B) Tucatinib Monotherapy (Cohort C)
Hide Arm/Group Description:
Tucatinib 300 mg PO BID on Days 1 to 21 of each 21-day cycle. Trastuzumab 8 mg/kg by IV infusion on Day 1 of Cycle 1 and 6 mg/kg on Day 1 of each subsequent cycle.
Randomized cohort. Tucatinib 300 mg PO BID on Days 1 to 21 of each 21-day cycle. Participants who do not respond to therapy may have the option to receive tucatinib and trastuzumab.
Overall Number of Participants Analyzed 85 29
Measure Type: Count of Participants
Unit of Measure: Participants
Hemoglobin decreased, Grade 1
28
  32.9%
6
  20.7%
Hemoglobin decreased, Grade 2
8
   9.4%
2
   6.9%
Hemoglobin decreased, Grade 3
3
   3.5%
0
   0.0%
Hemoglobin decreased, Grade 4
0
   0.0%
0
   0.0%
Leukocytes decreased, Grade 1
14
  16.5%
3
  10.3%
Leukocytes decreased, Grade 2
5
   5.9%
0
   0.0%
Leukocytes decreased, Grade 3
0
   0.0%
0
   0.0%
Leukocytes decreased, Grade 4
0
   0.0%
0
   0.0%
Neutrophils decreased, Grade 1
6
   7.1%
1
   3.4%
Neutrophils decreased, Grade 2
2
   2.4%
1
   3.4%
Neutrophils decreased, Grade 3
0
   0.0%
0
   0.0%
Neutrophils decreased, Grade 4
0
   0.0%
0
   0.0%
Platelets decreased, Grade 1
11
  12.9%
1
   3.4%
Platelets decreased, Grade 2
2
   2.4%
2
   6.9%
Platelets decreased, Grade 3
0
   0.0%
0
   0.0%
Platelets decreased, Grade 4
0
   0.0%
0
   0.0%
9.Secondary Outcome
Title Number of Participants With Treatment-Emergent Laboratory Abnormalities (Chemistry)
Hide Description Treatment emergent laboratory abnormalities are defined as abnormalities that are new or worsened on or after receiving the first dose of study treatment and up through 30 days after the last dose of study treatment. NCI CTCAE v5.0 is used for creatinine increased. NCI CTCAE v4.03 is used for the other lab parameters.
Time Frame Up to 49.3 months
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in the safety analysis set with both baseline and post-baseline results for each test.
Arm/Group Title Tucatinib+Trastuzumab (Cohorts A+B) Tucatinib Monotherapy (Cohort C)
Hide Arm/Group Description:
Tucatinib 300 mg PO BID on Days 1 to 21 of each 21-day cycle. Trastuzumab 8 mg/kg by IV infusion on Day 1 of Cycle 1 and 6 mg/kg on Day 1 of each subsequent cycle.
Randomized cohort. Tucatinib 300 mg PO BID on Days 1 to 21 of each 21-day cycle. Participants who do not respond to therapy may have the option to receive tucatinib and trastuzumab.
Overall Number of Participants Analyzed 85 29
Measure Type: Count of Participants
Unit of Measure: Participants
Potassium increased, Grade 1
5
   5.9%
1
   3.4%
Potassium increased, Grade 2
1
   1.2%
0
   0.0%
Potassium increased, Grade 3
0
   0.0%
1
   3.4%
Potassium increased, Grade 4
0
   0.0%
0
   0.0%
Potassium decreased, Grade 1
13
  15.3%
3
  10.3%
Potassium decreased, Grade 2
0
   0.0%
0
   0.0%
Potassium decreased, Grade 3
1
   1.2%
1
   3.4%
Potassium decreased, Grade 4
0
   0.0%
0
   0.0%
Aspartate Aminotransferase increased, Grade 1
20
  23.5%
6
  20.7%
Aspartate Aminotransferase increased, Grade 2
3
   3.5%
0
   0.0%
Aspartate Aminotransferase increased, Grade 3
2
   2.4%
2
   6.9%
Aspartate Aminotransferase increased, Grade 4
3
   3.5%
0
   0.0%
Alanine Aminotransferase increased, Grade 1
31
  36.5%
4
  13.8%
Alanine Aminotransferase increased, Grade 2
4
   4.7%
2
   6.9%
Alanine Aminotransferase increased, Grade 3
2
   2.4%
2
   6.9%
Alanine Aminotransferase increased, Grade 4
2
   2.4%
0
   0.0%
Creatinine increased, Grade 1
38
  44.7%
9
  31.0%
Creatinine increased, Grade 2
11
  12.9%
0
   0.0%
Creatinine increased, Grade 3
0
   0.0%
0
   0.0%
Creatinine increased, Grade 4
0
   0.0%
0
   0.0%
Alkaline Phosphatase increased, Grade 1
16
  18.8%
4
  13.8%
Alkaline Phosphatase increased, Grade 2
4
   4.7%
2
   6.9%
Alkaline Phosphatase increased, Grade 3
1
   1.2%
0
   0.0%
Alkaline Phosphatase increased, Grade 4
0
   0.0%
0
   0.0%
Total Bilirubin increased, Grade 1
14
  16.5%
6
  20.7%
Total Bilirubin increased, Grade 2
5
   5.9%
0
   0.0%
Total Bilirubin increased, Grade 3
3
   3.5%
0
   0.0%
Total Bilirubin increased, Grade 4
2
   2.4%
0
   0.0%
Time Frame Non-serious adverse events were followed during the safety reporting period (from study Day 1 (pre-dose) through 30 days after the last study treatment), which lasted for up to 49.3 months. All-cause mortality and serious adverse events (SAEs) were monitored for up to 53 months.
Adverse Event Reporting Description

Adverse events (AEs) for Cohorts A and B were analyzed together. All-cause mortality, SAE, and non-serious AE data are presented separately for Cohort C Pre-crossover and Post-crossover.

All-Cause Mortality is reported for all enrolled patients, regardless of whether or not they received study drug. SAEs and non-serious AEs are reported only for those patients who received at least one dose of study drug.
 
Arm/Group Title Tucatinib+Trastuzumab (Cohorts A+B) Cohort C (Pre-Crossover) Cohort C (Post-Crossover)
Hide Arm/Group Description Tucatinib 300 mg PO BID on Days 1 to 21 of each 21-day cycle. Trastuzumab 8 mg/kg by IV infusion on Day 1 of Cycle 1 and 6 mg/kg on Day 1 of each subsequent cycle. Randomized cohort. Tucatinib 300 mg PO BID on Days 1 to 21 of each 21-day cycle. Of the 30 participants who received tucatinib monotherapy, 28 crossed over to receive tucatinib + trastuzumab therapy.
All-Cause Mortality
Tucatinib+Trastuzumab (Cohorts A+B) Cohort C (Pre-Crossover) Cohort C (Post-Crossover)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   39/86 (45.35%)   2/31 (6.45%)   6/28 (21.43%) 
Hide Serious Adverse Events
Tucatinib+Trastuzumab (Cohorts A+B) Cohort C (Pre-Crossover) Cohort C (Post-Crossover)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   19/86 (22.09%)   3/30 (10.00%)   2/28 (7.14%) 
Cardiac disorders       
Angina unstable † 1  1/86 (1.16%)  0/30 (0.00%)  0/28 (0.00%) 
Cardiac failure † 1  0/86 (0.00%)  0/30 (0.00%)  1/28 (3.57%) 
Gastrointestinal disorders       
Abdominal pain † 1  2/86 (2.33%)  0/30 (0.00%)  0/28 (0.00%) 
Colitis † 1  1/86 (1.16%)  0/30 (0.00%)  0/28 (0.00%) 
Duodenal obstruction † 1  0/86 (0.00%)  1/30 (3.33%)  0/28 (0.00%) 
Dyspepsia † 1  1/86 (1.16%)  0/30 (0.00%)  0/28 (0.00%) 
Gastrointestinal obstruction † 1  1/86 (1.16%)  0/30 (0.00%)  0/28 (0.00%) 
Large intestinal obstruction † 1  3/86 (3.49%)  0/30 (0.00%)  0/28 (0.00%) 
Nausea † 1  1/86 (1.16%)  0/30 (0.00%)  0/28 (0.00%) 
Rectal perforation † 1  2/86 (2.33%)  0/30 (0.00%)  0/28 (0.00%) 
Small intestinal obstruction † 1  3/86 (3.49%)  0/30 (0.00%)  0/28 (0.00%) 
General disorders       
Fatigue † 1  1/86 (1.16%)  0/30 (0.00%)  0/28 (0.00%) 
Hepatobiliary disorders       
Bile duct stone † 1  1/86 (1.16%)  0/30 (0.00%)  0/28 (0.00%) 
Cholangitis † 1  1/86 (1.16%)  0/30 (0.00%)  0/28 (0.00%) 
Cholecystitis † 1  0/86 (0.00%)  0/30 (0.00%)  1/28 (3.57%) 
Infections and infestations       
COVID-19 pneumonia † 1  2/86 (2.33%)  0/30 (0.00%)  0/28 (0.00%) 
Kidney infection † 1  1/86 (1.16%)  0/30 (0.00%)  0/28 (0.00%) 
Pyelonephritis † 1  0/86 (0.00%)  1/30 (3.33%)  0/28 (0.00%) 
Sepsis † 1  1/86 (1.16%)  0/30 (0.00%)  0/28 (0.00%) 
Urinary tract infection † 1  3/86 (3.49%)  1/30 (3.33%)  0/28 (0.00%) 
Injury, poisoning and procedural complications       
Overdose † 1  0/86 (0.00%)  1/30 (3.33%)  0/28 (0.00%) 
Investigations       
Ejection fraction decreased † 1  0/86 (0.00%)  0/30 (0.00%)  1/28 (3.57%) 
Musculoskeletal and connective tissue disorders       
Back pain † 1  1/86 (1.16%)  0/30 (0.00%)  0/28 (0.00%) 
Flank pain † 1  1/86 (1.16%)  1/30 (3.33%)  0/28 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
Cancer pain † 1  1/86 (1.16%)  0/30 (0.00%)  0/28 (0.00%) 
Renal and urinary disorders       
Acute kidney injury † 1  1/86 (1.16%)  0/30 (0.00%)  0/28 (0.00%) 
Renal colic † 1  1/86 (1.16%)  0/30 (0.00%)  0/28 (0.00%) 
Respiratory, thoracic and mediastinal disorders       
Acute respiratory failure † 1  1/86 (1.16%)  0/30 (0.00%)  0/28 (0.00%) 
Vascular disorders       
Hypotension † 1  1/86 (1.16%)  0/30 (0.00%)  0/28 (0.00%) 
1
Term from vocabulary, MedDRA v24.0
†
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 2%
Tucatinib+Trastuzumab (Cohorts A+B) Cohort C (Pre-Crossover) Cohort C (Post-Crossover)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   82/86 (95.35%)   28/30 (93.33%)   23/28 (82.14%) 
Blood and lymphatic system disorders       
Anaemia † 1  9/86 (10.47%)  3/30 (10.00%)  2/28 (7.14%) 
Thrombocytopenia † 1  2/86 (2.33%)  0/30 (0.00%)  0/28 (0.00%) 
Ear and labyrinth disorders       
Vertigo † 1  0/86 (0.00%)  0/30 (0.00%)  1/28 (3.57%) 
Eye disorders       
Vision Blurred † 1  3/86 (3.49%)  0/30 (0.00%)  0/28 (0.00%) 
Blepharospasm † 1  2/86 (2.33%)  0/30 (0.00%)  0/28 (0.00%) 
Cataract † 1  0/86 (0.00%)  0/30 (0.00%)  1/28 (3.57%) 
Dry eye † 1  0/86 (0.00%)  0/30 (0.00%)  1/28 (3.57%) 
Eye pruritus † 1  0/86 (0.00%)  0/30 (0.00%)  1/28 (3.57%) 
Lacrimation increased † 1  0/86 (0.00%)  0/30 (0.00%)  1/28 (3.57%) 
Gastrointestinal disorders       
Abdominal distension † 1  2/86 (2.33%)  1/30 (3.33%)  1/28 (3.57%) 
Abdominal pain † 1  12/86 (13.95%)  6/30 (20.00%)  3/28 (10.71%) 
Abdominal pain upper † 1  4/86 (4.65%)  2/30 (6.67%)  2/28 (7.14%) 
Constipation † 1  12/86 (13.95%)  4/30 (13.33%)  1/28 (3.57%) 
Diarrhoea † 1  55/86 (63.95%)  10/30 (33.33%)  10/28 (35.71%) 
Flatulence † 1  3/86 (3.49%)  1/30 (3.33%)  1/28 (3.57%) 
Haematochezia † 1  0/86 (0.00%)  2/30 (6.67%)  0/28 (0.00%) 
Nausea † 1  29/86 (33.72%)  5/30 (16.67%)  2/28 (7.14%) 
Stomatitis † 1  0/86 (0.00%)  3/30 (10.00%)  1/28 (3.57%) 
Vomiting † 1  14/86 (16.28%)  2/30 (6.67%)  3/28 (10.71%) 
Dry mouth † 1  4/86 (4.65%)  0/30 (0.00%)  0/28 (0.00%) 
Dyspepsia † 1  3/86 (3.49%)  1/30 (3.33%)  0/28 (0.00%) 
Gastrooesophageal reflux disease † 1  3/86 (3.49%)  0/30 (0.00%)  1/28 (3.57%) 
Abdominal discomfort † 1  2/86 (2.33%)  0/30 (0.00%)  0/28 (0.00%) 
Gastrointestinal pain † 1  2/86 (2.33%)  0/30 (0.00%)  0/28 (0.00%) 
Rectal haemorrhage † 1  2/86 (2.33%)  1/30 (3.33%)  0/28 (0.00%) 
Abdominal pain lower † 1  0/86 (0.00%)  1/30 (3.33%)  0/28 (0.00%) 
Eructation † 1  0/86 (0.00%)  1/30 (3.33%)  0/28 (0.00%) 
Proctalgia † 1  0/86 (0.00%)  1/30 (3.33%)  0/28 (0.00%) 
Proctitis † 1  0/86 (0.00%)  1/30 (3.33%)  0/28 (0.00%) 
Salivary hypersecretion † 1  0/86 (0.00%)  1/30 (3.33%)  0/28 (0.00%) 
Toothache † 1  0/86 (0.00%)  1/30 (3.33%)  0/28 (0.00%) 
Glossodynia † 1  0/86 (0.00%)  0/30 (0.00%)  1/28 (3.57%) 
Oral pain † 1  0/86 (0.00%)  0/30 (0.00%)  1/28 (3.57%) 
Tooth loss † 1  0/86 (0.00%)  0/30 (0.00%)  1/28 (3.57%) 
General disorders       
Asthenia † 1  3/86 (3.49%)  5/30 (16.67%)  1/28 (3.57%) 
Chills † 1  16/86 (18.60%)  0/30 (0.00%)  2/28 (7.14%) 
Fatigue † 1  37/86 (43.02%)  6/30 (20.00%)  3/28 (10.71%) 
Influenza like illness † 1  7/86 (8.14%)  0/30 (0.00%)  1/28 (3.57%) 
Oedema peripheral † 1  7/86 (8.14%)  2/30 (6.67%)  1/28 (3.57%) 
Pyrexia † 1  17/86 (19.77%)  3/30 (10.00%)  5/28 (17.86%) 
Non-cardiac chest pain † 1  3/86 (3.49%)  0/30 (0.00%)  0/28 (0.00%) 
Peripheral swelling † 1  2/86 (2.33%)  0/30 (0.00%)  0/28 (0.00%) 
Xerosis † 1  0/86 (0.00%)  0/30 (0.00%)  1/28 (3.57%) 
Hepatobiliary disorders       
Cholecystitis † 1  0/86 (0.00%)  1/30 (3.33%)  0/28 (0.00%) 
Hepatic pain † 1  0/86 (0.00%)  1/30 (3.33%)  0/28 (0.00%) 
Infections and infestations       
COVID-19 † 1  5/86 (5.81%)  0/30 (0.00%)  0/28 (0.00%) 
Urinary tract infection † 1  4/86 (4.65%)  4/30 (13.33%)  3/28 (10.71%) 
COVID-19 pneumonia † 1  2/86 (2.33%)  0/30 (0.00%)  0/28 (0.00%) 
Herpes zoster † 1  2/86 (2.33%)  0/30 (0.00%)  1/28 (3.57%) 
Influenza † 1  2/86 (2.33%)  0/30 (0.00%)  0/28 (0.00%) 
Nail infection † 1  2/86 (2.33%)  0/30 (0.00%)  0/28 (0.00%) 
Rhinitis † 1  2/86 (2.33%)  0/30 (0.00%)  0/28 (0.00%) 
Kidney infection † 1  0/86 (0.00%)  1/30 (3.33%)  0/28 (0.00%) 
Conjunctivitis † 1  0/86 (0.00%)  0/30 (0.00%)  1/28 (3.57%) 
Furuncle † 1  0/86 (0.00%)  0/30 (0.00%)  1/28 (3.57%) 
Hordeolum † 1  0/86 (0.00%)  0/30 (0.00%)  1/28 (3.57%) 
Rash pustular † 1  0/86 (0.00%)  0/30 (0.00%)  1/28 (3.57%) 
Upper respiratory tract infection † 1  0/86 (0.00%)  0/30 (0.00%)  1/28 (3.57%) 
Injury, poisoning and procedural complications       
Infusion related reaction † 1  18/86 (20.93%)  0/30 (0.00%)  4/28 (14.29%) 
Fall † 1  3/86 (3.49%)  0/30 (0.00%)  0/28 (0.00%) 
Contusion † 1  0/86 (0.00%)  1/30 (3.33%)  0/28 (0.00%) 
Procedural pain † 1  0/86 (0.00%)  1/30 (3.33%)  0/28 (0.00%) 
Investigations       
Alanine aminotransferase increased † 1  5/86 (5.81%)  2/30 (6.67%)  2/28 (7.14%) 
Aspartate aminotransferase increased † 1  5/86 (5.81%)  3/30 (10.00%)  3/28 (10.71%) 
Weight decreased † 1  6/86 (6.98%)  3/30 (10.00%)  0/28 (0.00%) 
Ejection fraction decreased † 1  4/86 (4.65%)  0/30 (0.00%)  0/28 (0.00%) 
Blood creatinine increased † 1  3/86 (3.49%)  0/30 (0.00%)  1/28 (3.57%) 
Blood alkaline phosphatase increased † 1  2/86 (2.33%)  0/30 (0.00%)  0/28 (0.00%) 
Weight increased † 1  2/86 (2.33%)  1/30 (3.33%)  0/28 (0.00%) 
Metabolism and nutrition disorders       
Decreased appetite † 1  16/86 (18.60%)  4/30 (13.33%)  2/28 (7.14%) 
Dehydration † 1  7/86 (8.14%)  0/30 (0.00%)  1/28 (3.57%) 
Hypokalaemia † 1  5/86 (5.81%)  3/30 (10.00%)  0/28 (0.00%) 
Hyponatraemia † 1  3/86 (3.49%)  1/30 (3.33%)  0/28 (0.00%) 
Hypoalbuminaemia † 1  2/86 (2.33%)  0/30 (0.00%)  0/28 (0.00%) 
Hypocalcaemia † 1  0/86 (0.00%)  1/30 (3.33%)  0/28 (0.00%) 
Musculoskeletal and connective tissue disorders       
Arthralgia † 1  14/86 (16.28%)  2/30 (6.67%)  3/28 (10.71%) 
Back pain † 1  14/86 (16.28%)  1/30 (3.33%)  5/28 (17.86%) 
Hypercreatinaemia † 1  3/86 (3.49%)  1/30 (3.33%)  1/28 (3.57%) 
Muscle spasms † 1  6/86 (6.98%)  2/30 (6.67%)  3/28 (10.71%) 
Myalgia † 1  11/86 (12.79%)  2/30 (6.67%)  0/28 (0.00%) 
Pain in extremity † 1  8/86 (9.30%)  1/30 (3.33%)  1/28 (3.57%) 
Flank pain † 1  4/86 (4.65%)  0/30 (0.00%)  1/28 (3.57%) 
Musculoskeletal chest pain † 1  4/86 (4.65%)  0/30 (0.00%)  0/28 (0.00%) 
Muscular weakness † 1  2/86 (2.33%)  0/30 (0.00%)  0/28 (0.00%) 
Arthritis † 1  0/86 (0.00%)  1/30 (3.33%)  0/28 (0.00%) 
Musculoskeletal stiffness † 1  0/86 (0.00%)  1/30 (3.33%)  0/28 (0.00%) 
Nervous system disorders       
Dizziness † 1  4/86 (4.65%)  2/30 (6.67%)  0/28 (0.00%) 
Dysgeusia † 1  4/86 (4.65%)  1/30 (3.33%)  1/28 (3.57%) 
Headache † 1  8/86 (9.30%)  3/30 (10.00%)  2/28 (7.14%) 
Peripheral sensory neuropathy † 1  7/86 (8.14%)  1/30 (3.33%)  0/28 (0.00%) 
Hemiparesis † 1  0/86 (0.00%)  1/30 (3.33%)  0/28 (0.00%) 
Neurotoxicity † 1  0/86 (0.00%)  1/30 (3.33%)  0/28 (0.00%) 
Syncope † 1  0/86 (0.00%)  0/30 (0.00%)  1/28 (3.57%) 
Psychiatric disorders       
Anxiety † 1  9/86 (10.47%)  0/30 (0.00%)  0/28 (0.00%) 
Insomnia † 1  7/86 (8.14%)  1/30 (3.33%)  0/28 (0.00%) 
Renal and urinary disorders       
Dysuria † 1  3/86 (3.49%)  0/30 (0.00%)  2/28 (7.14%) 
Haematuria † 1  4/86 (4.65%)  0/30 (0.00%)  0/28 (0.00%) 
Nephrolithiasis † 1  4/86 (4.65%)  0/30 (0.00%)  0/28 (0.00%) 
Pollakiuria † 1  3/86 (3.49%)  0/30 (0.00%)  0/28 (0.00%) 
Reproductive system and breast disorders       
Pelvic pain † 1  2/86 (2.33%)  0/30 (0.00%)  0/28 (0.00%) 
Breast pain † 1  0/86 (0.00%)  1/30 (3.33%)  0/28 (0.00%) 
Vaginal haemorrhage † 1  0/86 (0.00%)  1/30 (3.33%)  0/28 (0.00%) 
Vulvovaginal dryness † 1  0/86 (0.00%)  0/30 (0.00%)  1/28 (3.57%) 
Respiratory, thoracic and mediastinal disorders       
Cough † 1  14/86 (16.28%)  2/30 (6.67%)  3/28 (10.71%) 
Dyspnoea † 1  12/86 (13.95%)  2/30 (6.67%)  2/28 (7.14%) 
Epistaxis † 1  6/86 (6.98%)  0/30 (0.00%)  1/28 (3.57%) 
Nasal congestion † 1  7/86 (8.14%)  0/30 (0.00%)  0/28 (0.00%) 
Productive cough † 1  6/86 (6.98%)  0/30 (0.00%)  1/28 (3.57%) 
Rhinitis allergic † 1  5/86 (5.81%)  0/30 (0.00%)  0/28 (0.00%) 
Upper-airway cough syndrome † 1  6/86 (6.98%)  0/30 (0.00%)  1/28 (3.57%) 
Oropharyngeal pain † 1  4/86 (4.65%)  0/30 (0.00%)  1/28 (3.57%) 
Rhinorrhoea † 1  3/86 (3.49%)  0/30 (0.00%)  0/28 (0.00%) 
Wheezing † 1  3/86 (3.49%)  0/30 (0.00%)  0/28 (0.00%) 
Dysphonia † 1  2/86 (2.33%)  0/30 (0.00%)  0/28 (0.00%) 
Dyspnoea exertional † 1  2/86 (2.33%)  0/30 (0.00%)  0/28 (0.00%) 
Pulmonary embolism † 1  2/86 (2.33%)  0/30 (0.00%)  0/28 (0.00%) 
Sinus pain † 1  2/86 (2.33%)  0/30 (0.00%)  0/28 (0.00%) 
Throat irritation † 1  0/86 (0.00%)  1/30 (3.33%)  0/28 (0.00%) 
Skin and subcutaneous tissue disorders       
Dermatitis acneiform † 1  16/86 (18.60%)  2/30 (6.67%)  0/28 (0.00%) 
Dry skin † 1  8/86 (9.30%)  0/30 (0.00%)  0/28 (0.00%) 
Onychomadesis † 1  2/86 (2.33%)  0/30 (0.00%)  0/28 (0.00%) 
Pruritus † 1  8/86 (9.30%)  1/30 (3.33%)  2/28 (7.14%) 
Rash maculo-papular † 1  7/86 (8.14%)  2/30 (6.67%)  1/28 (3.57%) 
Rash † 1  4/86 (4.65%)  0/30 (0.00%)  0/28 (0.00%) 
Erythema † 1  2/86 (2.33%)  0/30 (0.00%)  0/28 (0.00%) 
Nail disorder † 1  2/86 (2.33%)  0/30 (0.00%)  0/28 (0.00%) 
Urticaria † 1  2/86 (2.33%)  0/30 (0.00%)  0/28 (0.00%) 
Alopecia † 1  0/86 (0.00%)  1/30 (3.33%)  0/28 (0.00%) 
Pain of skin † 1  0/86 (0.00%)  1/30 (3.33%)  0/28 (0.00%) 
Onychoclasis † 1  0/86 (0.00%)  1/30 (3.33%)  1/28 (3.57%) 
Onycholysis † 1  0/86 (0.00%)  0/30 (0.00%)  1/28 (3.57%) 
Palmar-plantar erythrodysaesthesia syndrome † 1  0/86 (0.00%)  0/30 (0.00%)  1/28 (3.57%) 
Rash pruritic † 1  0/86 (0.00%)  0/30 (0.00%)  1/28 (3.57%) 
Social circumstances       
Pregnancy of partner † 1  0/86 (0.00%)  1/30 (3.33%)  0/28 (0.00%) 
Vascular disorders       
Hypertension † 1  15/86 (17.44%)  0/30 (0.00%)  0/28 (0.00%) 
Lymphoedema † 1  0/86 (0.00%)  0/30 (0.00%)  1/28 (3.57%) 
Thrombosis † 1  0/86 (0.00%)  0/30 (0.00%)  1/28 (3.57%) 
1
Term from vocabulary, MedDRA v24.0
†
Indicates events were collected by systematic assessment
[Not Specified]
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Chief Medical Officer
Organization: Seagen Inc.
Phone: (855)473-2436
EMail: medinfo@seagen.com
Layout table for additonal information
Responsible Party: Seagen Inc.
ClinicalTrials.gov Identifier: NCT03043313    
Other Study ID Numbers: SGNTUC-017
NCI-2017-01107 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
ACCRU-GI-1617 ( Other Identifier: Academic and Community Cancer Research United )
P30CA015083 ( U.S. NIH Grant/Contract )
First Submitted: January 31, 2017
First Posted: February 6, 2017
Results First Submitted: January 27, 2023
Results First Posted: April 18, 2023
Last Update Posted: November 13, 2023