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| ID | Type | Description | Link |
|---|---|---|---|
| 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 | View source |
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| Name | Class |
|---|---|
| National Cancer Institute (NCI) | NIH |
| Academic and Community Cancer Research United | OTHER |
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This trial studies how well the drug tucatinib works when given with trastuzumab and when given by itself. The participants in this trial have HER2-positive (HER2+) metastatic colorectal cancer (mCRC). 'Metastatic' means that the cancer has spread to other parts of the body.
In the first part of this study, participants enrolled into Cohort A and received both tucatinib and trastuzumab. In the second part of this study, participants are randomly assigned to either Cohort B or Cohort C. Participants in Cohort B will receive tucatinib and trastuzumab. Participants in Cohort C will receive tucatinib. Participants in Cohort C who do not respond to therapy may have an option to receive tucatinib plus trastuzumab.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Cohort A: Tucatinib + Trastuzumab | Experimental | Non-randomized cohort. Participants take tucatinib twice per day orally on Days 1-21 and trastuzumab intravenously (into the vein; IV) on Day 1. Cycles repeat every 21 days. |
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| Cohort B: Tucatinib + Trastuzumab | Experimental | Randomized cohort. Participants take tucatinib twice per day orally on Days 1-21 and trastuzumab intravenously (into the vein; IV) on Day 1. Cycles repeat every 21 days. |
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| Cohort C: Tucatinib Monotherapy | Experimental | Randomized cohort. Participants take tucatinib twice per orally every day. Participants who do not respond to therapy may have the option to receive tucatinib and trastuzumab. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Trastuzumab | Drug | Given intravenously (into the vein; IV) |
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| Measure | Description | Time Frame |
|---|---|---|
| Confirmed Objective Response Rate (cORR) Per RECIST v1.1 Per Blinded Independent Central Review (BICR) in Pooled Cohorts A+B | cORR was defined as the percentage of participants with confirmed CR or PR according to RECIST v1.1. CR was defined as the disappearance of all target lesions and each target lymph node must have reduction in short axis to less than (<)1.0 centimeter (cm). PR was defined as at least a 30 percentage (%) decrease in post-baseline sum of the diameters (sum of the longest diameter for all target lesions plus the sum of the short axis of all the target lymph nodes at current evaluation) taking as reference the baseline sum of diameters. | Up to 46.6 months |
| Measure | Description | Time Frame |
|---|---|---|
| ORR by 12 Weeks of Treatment Per RECIST v1.1 According to BICR Assessment | ORR per BICR by 12 Weeks was defined as the percentage of participants with CR or PR by 12 weeks of treatment, and before time of crossover (Cohort C), whichever came earlier. CR was defined as the disappearance of all target lesions and each target lymph node must have reduction in short axis to more than <1.0 cm. PR was defined as at least a 30% decrease in post-baseline sum of the diameters (sum of the longest diameter for all target lesions plus the sum of the short axis of all the target lymph nodes at current evaluation) taking as reference the baseline sum of diameter. |
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Inclusion Criteria
Histologically and/or cytologically documented adenocarcinoma of the colon or rectum that is metastatic and/or unresectable
Unless contraindicated, participants must have received and failed regimens containing the following agents: fluoropyrimidine (e.g., 5-fluorouracil or capecitabine), oxaliplatin, irinotecan, an anti-VEGF monoclonal antibody (bevacizumab, ramucirumab, or ziv-aflibercept), and an anti-PD-(L)1 therapy (nivolumab or pembrolizumab) if tumor has deficient mismatch repair proteins or is MSI-High.
Have progression of unresectable or metastatic CRC after the last systemic therapy, or be intolerant of last systemic therapy
Have RAS wild-type in primary or metastatic tumor tissue, based on expanded RAS testing
Willing and able to provide the most recently available tissue blocks obtained prior to treatment initiation. If archival tissue is not available, then a newly-obtained baseline biopsy of an accessible tumor
Have confirmed HER2-positive mCRC, as defined by having tumor tissue tested at a Clinical Laboratory Improvement Act (CLIA)-certified or International Organization for Standardization (ISO)-accredited laboratory, meeting at least one of the following criteria:
Have radiographically measurable disease assessable by RECIST 1.1, with at least one site of disease that is measurable and that has not been previously irradiated; or, if the participant has had previous radiation to the target lesion(s), there must be evidence of progression since the radiation
Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0, 1, or 2
Life expectancy greater than 3 months
Have adequate hematological, hepatic, renal, coagulation, and cardiac function
Exclusion Criteria
Previous treatment with anti-HER2 targeting therapy
Previous treatment with any systemic anticancer therapy, non-central nervous system radiation, or experimental agent within 3 weeks of first dose of study treatment
Toxicity related to prior cancer therapies that has not resolved to ≤ Grade 1, with the following exceptions:
Have clinically significant cardiopulmonary disease
Have known myocardial infarction, unstable angina, cardiac or other vascular stenting, angioplasty, or cardiac surgery within 6 months prior to first dose of study treatment
Major surgical procedure, open biopsy, or significant traumatic injury ≤28 days prior to enrollment (≤56 days for hepatectomy, open thoracotomy, or major neurosurgery) or anticipation of need for major surgical procedure during the study
Serious, non-healing wound, ulcer, or bone fracture
Known to be positive for hepatitis B by surface antigen expression
Known to have active hepatitis C infection
Known to be positive for human immunodeficiency virus (HIV)
Subjects who are pregnant, breastfeeding, or planning a pregnancy
Inability to swallow pills or any significant gastrointestinal disease which would preclude the adequate oral absorption of medications
Have used strong CYP2C8 inhibitor within 5 half-lives of the inhibitor, or have used a strong CYP2C8 or CYP3A4 inducer within 5 days prior to first dose of study treatment
History of another malignancy within 3 years before the first dose of study drug, or any evidence of residual disease from a previously diagnosed malignancy.
Subjects with known active CNS metastasis
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| Name | Affiliation | Role |
|---|---|---|
| John H Strickler | Academic and Community Cancer Research United | Study Chair |
| Jorge Ramos, DO | Seagen Inc. | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Alabama at Birmingham | Birmingham | Alabama | 35249 | United States | ||
| Banner MD Anderson Cancer Center |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 39368039 | Derived | Zhang D, Taylor A, Zhao JJ, Endres CJ, Topletz-Erickson A. Population Pharmacokinetic Analysis of Tucatinib in Healthy Participants and Patients with Breast Cancer or Colorectal Cancer. Clin Pharmacokinet. 2024 Oct;63(10):1477-1487. doi: 10.1007/s40262-024-01412-0. Epub 2024 Oct 5. | |
| 37941353 | Derived | Strickler JH, Bekaii-Saab TS. A study to learn how well tucatinib plus trastuzumab works for treating participants with metastatic colorectal cancer, and how safe it is: a plain language summary of the MOUNTAINEER study. Future Oncol. 2024 Mar;20(8):409-421. doi: 10.2217/fon-2023-0676. Epub 2023 Nov 8. |
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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 02-Nov-2023.
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| ID | Title | Description |
|---|---|---|
| FG000 | Tucatinib+Trastuzumab (Cohort A) | Non-randomized cohort. Participants received Tucatinib 300 milligrams (mg) orally (PO) twice daily (BID) on Days 1 to 21 of each 21-day cycle. Trastuzumab 8 milligram/kilogram (mg/kg) by intravenous (IV) infusion on Day 1 of Cycle 1 and 6 mg/kg on Day 1 of each subsequent cycle until progressive disease (PD), death, withdrawal of consent, study closure, or alternative therapy. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Mar 9, 2023 | Oct 31, 2024 |
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| Tucatinib | Drug | Given orally |
|
|
| Up to 3 months |
| Duration of Response (DOR) Per RECIST v1.1 According to BICR Assessment | DOR was defined as the time from the first objective response (CR or PR that is subsequently confirmed) to documented PD per RECIST v1.1 or death from any cause, whichever occurred first. CR was defined as the disappearance of all target lesions and each target lymph node must have reduction in short axis to more than <1.0 cm. PR was defined as at least a 30% decrease in post-baseline sum of the diameters (PBSD) (sum of the longest diameter for all target lesions plus the sum of the short axis of all the target lymph nodes at current evaluation) taking as reference the BSD. PD was defined as: at least one new malignant lesion, which also includes any lymph node that was normal at baseline (<1.0 cm short axis) and increased to more than or equal to (>=)1.0 cm short axis during follow-up or at least a 20% increase in PBSD taking as reference the minimum sum of the diameters (MSD). In addition, the PBSD must also demonstrate an absolute increase of at least 0.5 cm from the MSD. | Up to 64.1 months |
| Progression-Free Survival (PFS) Per RECIST v1.1 According to BICR Assessment for Pooled Cohorts A+B | PFS was 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 v1.1) or death from any cause, whichever occurred first. PD was defined as: at least one new malignant lesion, which also included any lymph node that was normal at baseline (<1.0 cm short axis) and increased to >=1.0 cm short axis during follow-up or at least a 20% increase in post-baseline sum of the diameters (PBSD) taking as reference the minimum sum of the diameters (MSD). In addition, the PBSD must also demonstrate an absolute increase of at least 0.5 cm from the MSD. | Up to 64.1 months |
| Overall Survival (OS) in Pooled Cohorts A+B | OS was defined as the time from start of study treatment (Cohort A) or randomization (Cohort B) to date of death due to any cause. | Up to 71.8 months |
| Number of Participants With Adverse Events (AEs): Interim Analysis | AE: Any untoward medical occurrence in a participant or clinical investigational participant administered a medicinal product and which does not necessarily have a causal relationship with this treatment. Treatment emergent AEs (TEAEs): Events that were 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). Serious AE (SAE): An event that at any dose led to death; life-threatening; required inpatient hospitalization/prolongation of existing hospitalization; persistent/significant disability/incapacity; congenital anomaly/birth defect/ important medical event. Treatment related AEs, SAEs, deaths also included. Relatedness was judged by investigator According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03: Grade(G) 3=severe AE, G4=life-threatening, urgent intervention indicated, G5=death related to AE. | Up to 49.3 months |
| Number of Participants With AEs: Final Analysis | AE: Any untoward medical occurrence in a participant or clinical investigational participant administered a medicinal product and which does not necessarily have a causal relationship with this treatment. Treatment emergent AEs (TEAEs): Events that were 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). SAE: An event that at any dose led to death; life-threatening; required inpatient hospitalization/prolongation of existing hospitalization; persistent/significant disability/incapacity; congenital anomaly/birth defect/ important medical event. Treatment related AEs, SAEs, deaths also included. Relatedness was judged by investigator According to NCI CTCAE version 4.03: Grade(G) 3=severe AE, G4=life-threatening, urgent intervention indicated, G5=death related to AE. | Up to 65.1 months |
| Number of Participants With AEs Resulting in Dose Modification: Interim Analysis | 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. | Up to 49.3 months |
| Number of Participants With AEs Resulting in Dose Modification: Final Analysis | 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. Drug interruption included infusion interrupted (full dose received within 24hrs). | Up to 65.1 months |
| Number of Participants With Treatment-Emergent Laboratory Abnormalities (Hematology): Interim Analysis | The following hematology laboratory parameters were assessed: Hemoglobin decreased; leukocytes decreased; neutrophils decreased and Platelets decreased. Treatment emergent laboratory abnormalities were defined as abnormalities that were 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 v4.03 was used for the lab parameters. Grade 1: mild; Grade 2: moderate; Grade 3: severe or clinically significant; Grade 4: life-threatening. | Up to 49.3 months |
| Number of Participants With Treatment-Emergent Laboratory Abnormalities (Hematology): Final Analysis | The following hematology laboratory parameters were assessed: Hemoglobin decreased; hemoglobin increased; leukocytes decreased; lymphocytes decreased; neutrophils decreased and Platelets decreased. Treatment emergent laboratory abnormalities were defined as abnormalities that were 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 v4.03 was used for the lab parameters. Grade 1: mild; Grade 2: moderate; Grade 3: severe or clinically significant; Grade 4: life-threatening. | Up to 65.1 months |
| Number of Participants With Treatment-Emergent Laboratory Abnormalities (Chemistry): Interim Analysis | The following chemistry laboratory parameters were assessed: Potassium increased; potassium decreased; aspartate aminotransferase increased; creatinine increased; alkaline phosphatase increased; total bilirubin increased. Treatment emergent laboratory abnormalities were defined as abnormalities that were 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 was used for creatinine increased. NCI CTCAE v4.03 was used for the other laboratory parameters. Grade 1: mild; Grade 2: moderate; Grade 3: severe or clinically significant; Grade 4: life-threatening. | Up to 49.3 months |
| Number of Participants With Treatment-Emergent Laboratory Abnormalities (Chemistry): Final Analysis | The following chemistry laboratory parameters were assessed: Potassium increased; potassium decreased; aspartate aminotransferase increased; creatinine increased; alkaline phosphatase increased; total bilirubin increased; albumin decreased; calcium corrected for albumin decreased; calcium corrected for albumin increased; glomerular filtration rate (GFR), estimated decreased; glucose decreased; glucose increased; sodium decreased; sodium increased; calcium and ionized increased. Treatment emergent laboratory abnormalities: Abnormalities that were 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 used for creatinine increased. NCI CTCAE v4.03 used for the other laboratory parameters. Grade 1: mild; Grade 2: moderate; Grade 3: severe or clinically significant; Grade 4: life-threatening. | Up to 65.1 months |
| Number of Participants With Clinically Significant Vital Signs: Final Analysis | Vital signs included temperature, oxygen saturation, systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate and weight. Vital signs were considered clinically significant: temperature: >= 38 degree Celsius (C); oxygen saturation less than (<)88%; SBP >=120 millimeters of mercury (mmHg) or DBP >=80 mmHg; SBP >=140 mmHg or DBP >=90 mmHg; SBP >=160 mmHg or DBP >=100 mmHg and heart rate >100 beats per minute (bpm) and maximum decrease from baseline in weight in kilograms (kg). | Up to 65.1 months |
| Gilbert |
| Arizona |
| 85234 |
| United States |
| Mayo Clinic Arizona | Phoenix | Arizona | 85054 | United States |
| Pacific Shores Medical Group | Long Beach | California | 90813 | United States |
| Keck Medical Center / University of Southern California | Los Angeles | California | 90033 | United States |
| Cedars Sinai Medical Center / Samuel Oschin Comprehensive Cancer Institute | Los Angeles | California | 90048 | United States |
| Stanford University School of Medicine | Palo Alto | California | 94304 | United States |
| Saint Joseph Heritage Medical Group | Santa Rosa | California | 95403 | United States |
| Rocky Mountain Cancer Centers - Aurora | Aurora | Colorado | 80012 | United States |
| Lombardi Cancer Center / Georgetown University Medical Center | Washington D.C. | District of Columbia | 20007 | United States |
| Florida Cancer Specialists - South Region | Fort Myers | Florida | 33901 | United States |
| Florida Cancer Specialists - North Region | St. Petersburg | Florida | 33705 | United States |
| Winship Cancer Institute / Emory University School of Medicine | Atlanta | Georgia | 30322 | United States |
| University of Chicago Medical Center | Chicago | Illinois | 60637-1470 | United States |
| Indiana University Simon Cancer Center | Indianapolis | Indiana | 46202 | United States |
| University of Iowa Hospitals and Clinics | Iowa City | Iowa | 52242 | United States |
| University of Kansas Cancer Center | Westwood | Kansas | 66205 | United States |
| Massachusetts General Hospital | Boston | Massachusetts | 02114 | United States |
| Dana Farber Cancer Institute | Boston | Massachusetts | 02215 | United States |
| Karmanos Cancer Institute / Wayne State University | Detroit | Michigan | 48201 | United States |
| Mayo Clinic Rochester | Rochester | Minnesota | 55905 | United States |
| Comprehensive Cancer Centers of Nevada | Las Vegas | Nevada | 89169 | United States |
| Roswell Park Cancer Institute | Buffalo | New York | 14203 | United States |
| Memorial Sloan Kettering Cancer Center | New York | New York | 10065 | United States |
| Duke University Medical Center | Durham | North Carolina | 27710 | United States |
| Case Western Reserve University / University Hospitals Cleveland Medical Center | Cleveland | Ohio | 44106 | United States |
| Northwest Cancer Specialists, P.C. | Portland | Oregon | 97227 | United States |
| Oregon Health and Science University | Portland | Oregon | 97239-3098 | United States |
| Allegheny General Hospital | Pittsburgh | Pennsylvania | 15212 | United States |
| Tennessee Oncology-Nashville/Sarah Cannon Research Institute | Nashville | Tennessee | 37203 | United States |
| Vanderbilt University Medical Center | Nashville | Tennessee | 37232 | United States |
| Texas Oncology - Beaumont | Beaumont | Texas | 77702-1449 | United States |
| Texas Oncology - Baylor Sammons Cancer Center | Dallas | Texas | 75246 | United States |
| Joe Arrington Cancer Research and Treatment Center | Lubbock | Texas | 79410 | United States |
| Texas Oncology - McAllen | McAllen | Texas | 78503 | United States |
| Texas Oncology - San Antonio Medical Center | San Antonio | Texas | 78240 | United States |
| Texas Oncology - Tyler | Tyler | Texas | 75702 | United States |
| Huntsman Cancer Institute/University of Utah | Salt Lake City | Utah | 84112 | United States |
| Providence Regional Medical Center Everett | Everett | Washington | 98201 | United States |
| Seattle Cancer Care Alliance / University of Washington | Seattle | Washington | 98109-1023 | United States |
| Aurora Research Institute Cancer Center | Milwaukee | Wisconsin | 53215 | United States |
| Cliniques Universitaires Saint Luc | Brussels | Other | 1200 | Belgium |
| Universitair Ziekenhuis Antwerpen | Edegem | Other | 2650 | Belgium |
| UZ Leuven campus Gasthuisberg | Leuven | Other | 3000 | Belgium |
| Hospitalier Jean Minjoz | Besançon | Other | 25030 | France |
| Center Georges Francois Leclerc | Dijon | Other | 21000 | France |
| Hôpital Franco-Britannique - Fondation Cognacq-Jay | Levallois-Perret | Other | 92300 | France |
| Centre Leon Berard - Centre regional de lutte contre le cancer Rhone-Alpes | Lyon | Other | 69373 | France |
| Hopital Saint-Antoine | Paris | Other | 75012 | France |
| Instituto Europeo di Oncologia | Milan | Other | 20141 | Italy |
| Niguarda Ca' Granda Hospital | Milan | Other | 20162 | Italy |
| Azienda Ospedaliero-Universitaria Pisana - Ospedale S. Chiara | Pisa | Other | 56126 | Italy |
| Hospital Universitario Vall d'Hebron | Barcelona | Other | 08035 | Spain |
| Institut Catala d'Oncologia - Hospital Duran i Reynals (ICO L'Hospitalet) | L'Hospitalet de Llobregat | Other | 08907 | Spain |
| Hospital General Universitario Gregorio Maranon | Madrid | Other | 28007 | Spain |
| Hospital Clinico Universitario de Valencia | Valencia | Other | 46010 | Spain |
| 37318379 | Derived | Casak SJ, Horiba MN, Yuan M, Cheng J, Lemery SJ, Shen YL, Fu W, Moore JN, Li Y, Bi Y, Auth D, Fesenko N, Kluetz PG, Pazdur R, Fashoyin-Aje LA. FDA Approval Summary: Tucatinib with Trastuzumab for Advanced Unresectable or Metastatic, Chemotherapy Refractory, HER2-Positive RAS Wild-Type Colorectal Cancer. Clin Cancer Res. 2023 Nov 1;29(21):4326-4330. doi: 10.1158/1078-0432.CCR-23-1041. |
| 37142372 | Derived | Strickler JH, Cercek A, Siena S, Andre T, Ng K, Van Cutsem E, Wu C, Paulson AS, Hubbard JM, Coveler AL, Fountzilas C, Kardosh A, Kasi PM, Lenz HJ, Ciombor KK, Elez E, Bajor DL, Cremolini C, Sanchez F, Stecher M, Feng W, Bekaii-Saab TS; MOUNTAINEER investigators. Tucatinib plus trastuzumab for chemotherapy-refractory, HER2-positive, RAS wild-type unresectable or metastatic colorectal cancer (MOUNTAINEER): a multicentre, open-label, phase 2 study. Lancet Oncol. 2023 May;24(5):496-508. doi: 10.1016/S1470-2045(23)00150-X. |
| FG001 | Tucatinib+Trastuzumab (Cohort B) | Randomized cohort. Participants received 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 until PD, death, withdrawal of consent, study closure, or alternative therapy. |
| FG002 | Tucatinib Monotherapy (Cohort C) | Participants received Tucatinib 300 mg PO BID on Days 1 to 21 of each 21-day cycle. Participants who did not respond to monotherapy were given the option to receive tucatinib and trastuzumab until PD, death, withdrawal of consent, study closure, or alternative therapy based on radiographic progression (as determined by investigator assessment using response evaluation criteria in solid tumors [RECIST] version [v] 1.1), or if they had not achieved a partial response (PR) or complete response (CR) by the week 12 assessment. |
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| NOT COMPLETED |
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The Full Analysis Set included all participants who were enrolled and received any amount of study treatment and had human epidermal growth factor receptor 2+ (HER2+) tumors as defined by one or more protocol required local tests.
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| ID | Title | Description |
|---|---|---|
| BG000 | Tucatinib+Trastuzumab (Cohort A) | Non-randomized cohort. Participants received 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 until PD, death, withdrawal of consent, study closure, or alternative therapy. |
| BG001 | Tucatinib+Trastuzumab (Cohort B) | Randomized cohort. Participants received 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 until PD, death, withdrawal of consent, study closure, or alternative therapy. |
| BG002 | Tucatinib Monotherapy (Cohort C) | Participants received Tucatinib 300 mg PO BID on Days 1 to 21 of each 21-day cycle. Participants who did not respond to monotherapy were given the option to receive tucatinib and trastuzumab until PD, death, withdrawal of consent, study closure, or alternative therapy based on radiographic progression (as determined by investigator assessment using RECIST v1.1), or if they had not achieved a PR or CR by the week 12 assessment. |
| BG003 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Median | Full Range | Years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Eastern Cooperative Oncology Group (ECOG) Performance Status | ECOG performance status was used to assess participants disease progression, and ability to carry out daily living activities. 0=Normal activity; 1=Symptoms but ambulatory; 2=In bed less than (<)50 percent (%) of the time; 3= In bed >50% of the time; 4=100% bedridden; 5=Dead. | Count of Participants | Participants |
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| Region of Enrollment | Count of Participants | Participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Confirmed Objective Response Rate (cORR) Per RECIST v1.1 Per Blinded Independent Central Review (BICR) in Pooled Cohorts A+B | cORR was defined as the percentage of participants with confirmed CR or PR according to RECIST v1.1. CR was defined as the disappearance of all target lesions and each target lymph node must have reduction in short axis to less than (<)1.0 centimeter (cm). PR was defined as at least a 30 percentage (%) decrease in post-baseline sum of the diameters (sum of the longest diameter for all target lesions plus the sum of the short axis of all the target lymph nodes at current evaluation) taking as reference the baseline sum of diameters. | The Full Analysis Set included all participants who were enrolled and received any amount of study treatment and had HER2+ tumors as defined by one or more protocol required local tests. Data for cohort A and B was combined as prespecified in the statistical analysis plan (SAP). | Posted | Number | 95% Confidence Interval | Percentage of Participants | Up to 46.6 months |
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| Secondary | ORR by 12 Weeks of Treatment Per RECIST v1.1 According to BICR Assessment | ORR per BICR by 12 Weeks was defined as the percentage of participants with CR or PR by 12 weeks of treatment, and before time of crossover (Cohort C), whichever came earlier. CR was defined as the disappearance of all target lesions and each target lymph node must have reduction in short axis to more than <1.0 cm. PR was defined as at least a 30% decrease in post-baseline sum of the diameters (sum of the longest diameter for all target lesions plus the sum of the short axis of all the target lymph nodes at current evaluation) taking as reference the baseline sum of diameter. | The Full Analysis Set included all participants who were enrolled and received any amount of study treatment and had HER2+ tumors as defined by one or more protocol required local tests. Data for cohort A and B was combined as prespecified in SAP. | Posted | Number | 95% Confidence Interval | Percentage of Participants | Up to 3 months |
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| Secondary | Duration of Response (DOR) Per RECIST v1.1 According to BICR Assessment | DOR was defined as the time from the first objective response (CR or PR that is subsequently confirmed) to documented PD per RECIST v1.1 or death from any cause, whichever occurred first. CR was defined as the disappearance of all target lesions and each target lymph node must have reduction in short axis to more than <1.0 cm. PR was defined as at least a 30% decrease in post-baseline sum of the diameters (PBSD) (sum of the longest diameter for all target lesions plus the sum of the short axis of all the target lymph nodes at current evaluation) taking as reference the BSD. PD was defined as: at least one new malignant lesion, which also includes any lymph node that was normal at baseline (<1.0 cm short axis) and increased to more than or equal to (>=)1.0 cm short axis during follow-up or at least a 20% increase in PBSD taking as reference the minimum sum of the diameters (MSD). In addition, the PBSD must also demonstrate an absolute increase of at least 0.5 cm from the MSD. | The Full Analysis Set included all participants who were enrolled and received any amount of study treatment and had HER2+ tumors as defined by one or more protocol required local tests. Data for cohort A and B was combined as prespecified in SAP. Here, "Number of Participants Analyzed" signifies participants who had CR or PR. | Posted | Median | 95% Confidence Interval | Months | Up to 64.1 months |
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| Secondary | Progression-Free Survival (PFS) Per RECIST v1.1 According to BICR Assessment for Pooled Cohorts A+B | PFS was 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 v1.1) or death from any cause, whichever occurred first. PD was defined as: at least one new malignant lesion, which also included any lymph node that was normal at baseline (<1.0 cm short axis) and increased to >=1.0 cm short axis during follow-up or at least a 20% increase in post-baseline sum of the diameters (PBSD) taking as reference the minimum sum of the diameters (MSD). In addition, the PBSD must also demonstrate an absolute increase of at least 0.5 cm from the MSD. | The Full Analysis Set included all participants who were enrolled and received any amount of study treatment and had HER2+ tumors as defined by one or more protocol required local tests. Data for cohort A and B was combined as prespecified in SAP. | Posted | Median | 95% Confidence Interval | Months | Up to 64.1 months |
|
| ||||||||||||||||||||||||||
| Secondary | Overall Survival (OS) in Pooled Cohorts A+B | OS was defined as the time from start of study treatment (Cohort A) or randomization (Cohort B) to date of death due to any cause. | The Full Analysis Set included all participants who were enrolled and received any amount of study treatment and had HER2+ tumors as defined by one or more protocol required local tests. Data for cohort A and B was combined as prespecified in SAP. | Posted | Median | 95% Confidence Interval | Months | Up to 71.8 months |
|
| ||||||||||||||||||||||||||
| Secondary | Number of Participants With Adverse Events (AEs): Interim Analysis | AE: Any untoward medical occurrence in a participant or clinical investigational participant administered a medicinal product and which does not necessarily have a causal relationship with this treatment. Treatment emergent AEs (TEAEs): Events that were 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). Serious AE (SAE): An event that at any dose led to death; life-threatening; required inpatient hospitalization/prolongation of existing hospitalization; persistent/significant disability/incapacity; congenital anomaly/birth defect/ important medical event. Treatment related AEs, SAEs, deaths also included. Relatedness was judged by investigator According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03: Grade(G) 3=severe AE, G4=life-threatening, urgent intervention indicated, G5=death related to AE. | The safety analysis set included participants who received any amount of study treatment. Data for cohort A and B was combined as prespecified in SAP. | Posted | Count of Participants | Participants | Up to 49.3 months |
| ||||||||||||||||||||||||||||
| Secondary | Number of Participants With AEs: Final Analysis | AE: Any untoward medical occurrence in a participant or clinical investigational participant administered a medicinal product and which does not necessarily have a causal relationship with this treatment. Treatment emergent AEs (TEAEs): Events that were 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). SAE: An event that at any dose led to death; life-threatening; required inpatient hospitalization/prolongation of existing hospitalization; persistent/significant disability/incapacity; congenital anomaly/birth defect/ important medical event. Treatment related AEs, SAEs, deaths also included. Relatedness was judged by investigator According to NCI CTCAE version 4.03: Grade(G) 3=severe AE, G4=life-threatening, urgent intervention indicated, G5=death related to AE. | The safety analysis set included participants who received any amount of study treatment. Data for cohort A and B was combined as prespecified in SAP. | Posted | Count of Participants | Participants | Up to 65.1 months |
| ||||||||||||||||||||||||||||
| Secondary | Number of Participants With AEs Resulting in Dose Modification: Interim Analysis | 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. | The safety analysis set included participants who received any amount of study treatment. Data for cohort A and B was combined as prespecified in SAP. | Posted | Count of Participants | Participants | Up to 49.3 months |
| ||||||||||||||||||||||||||||
| Secondary | Number of Participants With AEs Resulting in Dose Modification: Final Analysis | 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. Drug interruption included infusion interrupted (full dose received within 24hrs). | The safety analysis set included participants who received any amount of study treatment. Data for cohorts A and B was combined as prespecified in SAP. | Posted | Count of Participants | Participants | Up to 65.1 months |
| ||||||||||||||||||||||||||||
| Secondary | Number of Participants With Treatment-Emergent Laboratory Abnormalities (Hematology): Interim Analysis | The following hematology laboratory parameters were assessed: Hemoglobin decreased; leukocytes decreased; neutrophils decreased and Platelets decreased. Treatment emergent laboratory abnormalities were defined as abnormalities that were 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 v4.03 was used for the lab parameters. Grade 1: mild; Grade 2: moderate; Grade 3: severe or clinically significant; Grade 4: life-threatening. | The safety analysis set included all participants who received any amount of study treatment. Data for cohorts A and B was combined as prespecified in SAP. Here, "Number of Participants Analyzed" signifies participants evaluable for this outcome measure. | Posted | Count of Participants | Participants | Up to 49.3 months |
| ||||||||||||||||||||||||||||
| Secondary | Number of Participants With Treatment-Emergent Laboratory Abnormalities (Hematology): Final Analysis | The following hematology laboratory parameters were assessed: Hemoglobin decreased; hemoglobin increased; leukocytes decreased; lymphocytes decreased; neutrophils decreased and Platelets decreased. Treatment emergent laboratory abnormalities were defined as abnormalities that were 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 v4.03 was used for the lab parameters. Grade 1: mild; Grade 2: moderate; Grade 3: severe or clinically significant; Grade 4: life-threatening. | The safety analysis set included all participants who received any amount of study treatment. Data for cohorts A and B was combined as prespecified in SAP. Here, "Number of Participants Analyzed" signifies participants evaluable for this outcome measure. | Posted | Count of Participants | Participants | Up to 65.1 months |
| ||||||||||||||||||||||||||||
| Secondary | Number of Participants With Treatment-Emergent Laboratory Abnormalities (Chemistry): Interim Analysis | The following chemistry laboratory parameters were assessed: Potassium increased; potassium decreased; aspartate aminotransferase increased; creatinine increased; alkaline phosphatase increased; total bilirubin increased. Treatment emergent laboratory abnormalities were defined as abnormalities that were 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 was used for creatinine increased. NCI CTCAE v4.03 was used for the other laboratory parameters. Grade 1: mild; Grade 2: moderate; Grade 3: severe or clinically significant; Grade 4: life-threatening. | The safety analysis set included all participants who received any amount of study treatment. Data for cohorts A and B was combined as prespecified in SAP. Here, "Number of Participants Analyzed" signifies participants evaluable for this outcome measure. | Posted | Count of Participants | Participants | Up to 49.3 months |
| ||||||||||||||||||||||||||||
| Secondary | Number of Participants With Treatment-Emergent Laboratory Abnormalities (Chemistry): Final Analysis | The following chemistry laboratory parameters were assessed: Potassium increased; potassium decreased; aspartate aminotransferase increased; creatinine increased; alkaline phosphatase increased; total bilirubin increased; albumin decreased; calcium corrected for albumin decreased; calcium corrected for albumin increased; glomerular filtration rate (GFR), estimated decreased; glucose decreased; glucose increased; sodium decreased; sodium increased; calcium and ionized increased. Treatment emergent laboratory abnormalities: Abnormalities that were 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 used for creatinine increased. NCI CTCAE v4.03 used for the other laboratory parameters. Grade 1: mild; Grade 2: moderate; Grade 3: severe or clinically significant; Grade 4: life-threatening. | The safety analysis set included all participants who received any amount of study treatment. Data for cohorts A and B was combined as prespecified in SAP. Here, "Number of Participants Analyzed" signifies participants evaluable for this outcome measure and "Number Analyzed" signifies number evaluable for specified rows. | Posted | Count of Participants | Participants | Up to 65.1 months |
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| Secondary | Number of Participants With Clinically Significant Vital Signs: Final Analysis | Vital signs included temperature, oxygen saturation, systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate and weight. Vital signs were considered clinically significant: temperature: >= 38 degree Celsius (C); oxygen saturation less than (<)88%; SBP >=120 millimeters of mercury (mmHg) or DBP >=80 mmHg; SBP >=140 mmHg or DBP >=90 mmHg; SBP >=160 mmHg or DBP >=100 mmHg and heart rate >100 beats per minute (bpm) and maximum decrease from baseline in weight in kilograms (kg). | The safety analysis set included participants who received any amount of study treatment. Data for cohorts A and B was combined as prespecified in SAP. | Posted | Count of Participants | Participants | Up to 65.1 months |
|
All-cause mortality: From start of study treatment to death by any cause (maximum up to 71.8 months); adverse events were followed during the safety reporting period (from Day 1 through 30 days after the last dose of study treatment) maximum up to 65.1 months
Adverse events (AEs) for Cohorts A and B were analyzed together as prespecified in SAP. All-Cause Mortality is reported for all enrolled participants, regardless of whether or not they received study drug. SAEs and non-serious AEs are reported only for those participants who received at least one dose of study drug.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Tucatinib+Trastuzumab (Cohorts A+B) | Participants received 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 until PD, death, withdrawal of consent, study closure, or alternative therapy. | 54 | 86 | 20 | 86 | 82 | 86 |
| EG001 | Tucatinib Pre-Crossover (Cohort C) | Participants received Tucatinib 300 mg PO BID on Days 1 to 21 of each 21-day cycle. Participants who did not respond to monotherapy were given the option to receive tucatinib and trastuzumab based on radiographic progression (as determined by investigator assessment using RECIST v1.1), or if they had not achieved a PR or CR by the week 12 assessment. | 2 | 31 | 3 | 30 | 28 | 30 |
| EG002 | Tucatinib Post-Crossover (Cohort C) | Participants received 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 until PD, death, withdrawal of consent, study closure, or alternative therapy. | 15 | 28 | 6 | 28 | 23 | 28 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Angina unstable | Cardiac disorders | MedDRA v26.1 | Systematic Assessment |
| |
| Cardiac failure | Cardiac disorders | MedDRA v26.1 | Systematic Assessment |
| |
| Abdominal pain | Gastrointestinal disorders | MedDRA v26.1 | Systematic Assessment |
| |
| Colitis | Gastrointestinal disorders | MedDRA v26.1 | Systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | MedDRA v26.1 | Systematic Assessment |
| |
| Dyspepsia | Gastrointestinal disorders | MedDRA v26.1 | Systematic Assessment |
| |
| Gastrointestinal obstruction | Gastrointestinal disorders | MedDRA v26.1 | Systematic Assessment |
| |
| Large intestinal obstruction | Gastrointestinal disorders | MedDRA v26.1 | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA v26.1 | Systematic Assessment |
| |
| Rectal perforation | Gastrointestinal disorders | MedDRA v26.1 | Systematic Assessment |
| |
| Small intestinal obstruction | Gastrointestinal disorders | MedDRA v26.1 | Systematic Assessment |
| |
| Fatigue | General disorders | MedDRA v26.1 | Systematic Assessment |
| |
| Malaise | General disorders | MedDRA v26.1 | Systematic Assessment |
| |
| Bile duct stone | Hepatobiliary disorders | MedDRA v26.1 | Systematic Assessment |
| |
| Cholangitis | Hepatobiliary disorders | MedDRA v26.1 | Systematic Assessment |
| |
| Cholecystitis | Hepatobiliary disorders | MedDRA v26.1 | Systematic Assessment |
| |
| Anorectal infection | Infections and infestations | MedDRA v26.1 | Systematic Assessment |
| |
| COVID-19 pneumonia | Infections and infestations | MedDRA v26.1 | Systematic Assessment |
| |
| Kidney infection | Infections and infestations | MedDRA v26.1 | Systematic Assessment |
| |
| Sepsis | Infections and infestations | MedDRA v26.1 | Systematic Assessment |
| |
| Urinary tract infection | Infections and infestations | MedDRA v26.1 | Systematic Assessment |
| |
| Urinary tract infection bacterial | Infections and infestations | MedDRA v26.1 | Systematic Assessment |
| |
| Humerus fracture | Injury, poisoning and procedural complications | MedDRA v26.1 | Systematic Assessment |
| |
| Radius fracture | Injury, poisoning and procedural complications | MedDRA v26.1 | Systematic Assessment |
| |
| Ulna fracture | Injury, poisoning and procedural complications | MedDRA v26.1 | Systematic Assessment |
| |
| Ejection fraction decreased | Investigations | MedDRA v26.1 | Systematic Assessment |
| |
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA v26.1 | Systematic Assessment |
| |
| Flank pain | Musculoskeletal and connective tissue disorders | MedDRA v26.1 | Systematic Assessment |
| |
| Cancer pain | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA v26.1 | Systematic Assessment |
| |
| Cerebellar haemorrhage | Nervous system disorders | MedDRA v26.1 | Systematic Assessment |
| |
| Peripheral sensorimotor neuropathy | Nervous system disorders | MedDRA v26.1 | Systematic Assessment |
| |
| Acute kidney injury | Renal and urinary disorders | MedDRA v26.1 | Systematic Assessment |
| |
| Renal colic | Renal and urinary disorders | MedDRA v26.1 | Systematic Assessment |
| |
| Acute respiratory failure | Respiratory, thoracic and mediastinal disorders | MedDRA v26.1 | Systematic Assessment |
| |
| Hypotension | Vascular disorders | MedDRA v26.1 | Systematic Assessment |
| |
| Duodenal obstruction | Gastrointestinal disorders | MedDRA v26.1 | Systematic Assessment |
| |
| Pyelonephritis | Infections and infestations | MedDRA v26.1 | Systematic Assessment |
| |
| Overdose | Injury, poisoning and procedural complications | MedDRA v26.1 | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA v26.1 | Systematic Assessment |
| |
| Lacrimation increased | Eye disorders | MedDRA v26.1 | Systematic Assessment |
| |
| Abdominal discomfort | Gastrointestinal disorders | MedDRA v26.1 | Systematic Assessment |
| |
| Abdominal distension | Gastrointestinal disorders | MedDRA v26.1 | Systematic Assessment |
| |
| Abdominal pain | Gastrointestinal disorders | MedDRA v26.1 | Systematic Assessment |
| |
| Abdominal pain lower | Gastrointestinal disorders | MedDRA v26.1 | Systematic Assessment |
| |
| Abdominal pain upper | Gastrointestinal disorders | MedDRA v26.1 | Systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | MedDRA v26.1 | Systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA v26.1 | Systematic Assessment |
| |
| Flatulence | Gastrointestinal disorders | MedDRA v26.1 | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA v26.1 | Systematic Assessment |
| |
| Oral pain | Gastrointestinal disorders | MedDRA v26.1 | Systematic Assessment |
| |
| Proctalgia | Gastrointestinal disorders | MedDRA v26.1 | Systematic Assessment |
| |
| Stomatitis | Gastrointestinal disorders | MedDRA v26.1 | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA v26.1 | Systematic Assessment |
| |
| Asthenia | General disorders | MedDRA v26.1 | Systematic Assessment |
| |
| Chills | General disorders | MedDRA v26.1 | Systematic Assessment |
| |
| Fatigue | General disorders | MedDRA v26.1 | Systematic Assessment |
| |
| Influenza like illness | General disorders | MedDRA v26.1 | Systematic Assessment |
| |
| Oedema peripheral | General disorders | MedDRA v26.1 | Systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA v26.1 | Systematic Assessment |
| |
| COVID-19 | Infections and infestations | MedDRA v26.1 | Systematic Assessment |
| |
| Upper respiratory tract infection | Infections and infestations | MedDRA v26.1 | Systematic Assessment |
| |
| Urinary tract infection | Infections and infestations | MedDRA v26.1 | Systematic Assessment |
| |
| Infusion related reaction | Injury, poisoning and procedural complications | MedDRA v26.1 | Systematic Assessment |
| |
| Alanine aminotransferase increased | Investigations | MedDRA v26.1 | Systematic Assessment |
| |
| Aspartate aminotransferase increased | Investigations | MedDRA v26.1 | Systematic Assessment |
| |
| Ejection fraction decreased | Investigations | MedDRA v26.1 | Systematic Assessment |
| |
| Weight decreased | Investigations | MedDRA v26.1 | Systematic Assessment |
| |
| Decreased appetite | Metabolism and nutrition disorders | MedDRA v26.1 | Systematic Assessment |
| |
| Dehydration | Metabolism and nutrition disorders | MedDRA v26.1 | Systematic Assessment |
| |
| Hypokalaemia | Metabolism and nutrition disorders | MedDRA v26.1 | Systematic Assessment |
| |
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA v26.1 | Systematic Assessment |
| |
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA v26.1 | Systematic Assessment |
| |
| Hypercreatinaemia | Musculoskeletal and connective tissue disorders | MedDRA v26.1 | Systematic Assessment |
| |
| Muscle spasms | Musculoskeletal and connective tissue disorders | MedDRA v26.1 | Systematic Assessment |
| |
| Musculoskeletal chest pain | Musculoskeletal and connective tissue disorders | MedDRA v26.1 | Systematic Assessment |
| |
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA v26.1 | Systematic Assessment |
| |
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA v26.1 | Systematic Assessment |
| |
| Dizziness | Nervous system disorders | MedDRA v26.1 | Systematic Assessment |
| |
| Dysgeusia | Nervous system disorders | MedDRA v26.1 | Systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA v26.1 | Systematic Assessment |
| |
| Peripheral sensory neuropathy | Nervous system disorders | MedDRA v26.1 | Systematic Assessment |
| |
| Anxiety | Psychiatric disorders | MedDRA v26.1 | Systematic Assessment |
| |
| Insomnia | Psychiatric disorders | MedDRA v26.1 | Systematic Assessment |
| |
| Dysuria | Renal and urinary disorders | MedDRA v26.1 | Systematic Assessment |
| |
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA v26.1 | Systematic Assessment |
| |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA v26.1 | Systematic Assessment |
| |
| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA v26.1 | Systematic Assessment |
| |
| Nasal congestion | Respiratory, thoracic and mediastinal disorders | MedDRA v26.1 | Systematic Assessment |
| |
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA v26.1 | Systematic Assessment |
| |
| Productive cough | Respiratory, thoracic and mediastinal disorders | MedDRA v26.1 | Systematic Assessment |
| |
| Rhinitis allergic | Respiratory, thoracic and mediastinal disorders | MedDRA v26.1 | Systematic Assessment |
| |
| Upper-airway cough syndrome | Respiratory, thoracic and mediastinal disorders | MedDRA v26.1 | Systematic Assessment |
| |
| Dermatitis acneiform | Skin and subcutaneous tissue disorders | MedDRA v26.1 | Systematic Assessment |
| |
| Dry skin | Skin and subcutaneous tissue disorders | MedDRA v26.1 | Systematic Assessment |
| |
| Nail disorder | Skin and subcutaneous tissue disorders | MedDRA v26.1 | Systematic Assessment |
| |
| Onychoclasis | Skin and subcutaneous tissue disorders | MedDRA v26.1 | Systematic Assessment |
| |
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA v26.1 | Systematic Assessment |
| |
| Rash maculo-papular | Skin and subcutaneous tissue disorders | MedDRA v26.1 | Systematic Assessment |
| |
| Hypertension | Vascular disorders | MedDRA v26.1 | Systematic Assessment |
| |
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA v26.1 | Systematic Assessment |
| |
| Arrhythmia | Cardiac disorders | MedDRA v26.1 | Systematic Assessment |
| |
| Meniere's disease | Ear and labyrinth disorders | MedDRA v26.1 | Systematic Assessment |
| |
| Vertigo | Ear and labyrinth disorders | MedDRA v26.1 | Systematic Assessment |
| |
| Blepharospasm | Eye disorders | MedDRA v26.1 | Systematic Assessment |
| |
| Cataract | Eye disorders | MedDRA v26.1 | Systematic Assessment |
| |
| Dry eye | Eye disorders | MedDRA v26.1 | Systematic Assessment |
| |
| Eye pruritus | Eye disorders | MedDRA v26.1 | Systematic Assessment |
| |
| Vision blurred | Eye disorders | MedDRA v26.1 | Systematic Assessment |
| |
| Dry mouth | Gastrointestinal disorders | MedDRA v26.1 | Systematic Assessment |
| |
| Dyspepsia | Gastrointestinal disorders | MedDRA v26.1 | Systematic Assessment |
| |
| Food poisoning | Gastrointestinal disorders | MedDRA v26.1 | Systematic Assessment |
| |
| Gastrointestinal pain | Gastrointestinal disorders | MedDRA v26.1 | Systematic Assessment |
| |
| Gastrooesophageal reflux disease | Gastrointestinal disorders | MedDRA v26.1 | Systematic Assessment |
| |
| Glossodynia | Gastrointestinal disorders | MedDRA v26.1 | Systematic Assessment |
| |
| Noninfective gingivitis | Gastrointestinal disorders | MedDRA v26.1 | Systematic Assessment |
| |
| Rectal haemorrhage | Gastrointestinal disorders | MedDRA v26.1 | Systematic Assessment |
| |
| Tooth loss | Gastrointestinal disorders | MedDRA v26.1 | Systematic Assessment |
| |
| Non-cardiac chest pain | General disorders | MedDRA v26.1 | Systematic Assessment |
| |
| Pain | General disorders | MedDRA v26.1 | Systematic Assessment |
| |
| Peripheral swelling | General disorders | MedDRA v26.1 | Systematic Assessment |
| |
| Seasonal allergy | Immune system disorders | MedDRA v26.1 | Systematic Assessment |
| |
| Conjunctivitis | Infections and infestations | MedDRA v26.1 | Systematic Assessment |
| |
| Gastroenteritis | Infections and infestations | MedDRA v26.1 | Systematic Assessment |
| |
| Gingival abscess | Infections and infestations | MedDRA v26.1 | Systematic Assessment |
| |
| Herpes zoster | Infections and infestations | MedDRA v26.1 | Systematic Assessment |
| |
| Hordeolum | Infections and infestations | MedDRA v26.1 | Systematic Assessment |
| |
| Influenza | Infections and infestations | MedDRA v26.1 | Systematic Assessment |
| |
| Nail infection | Infections and infestations | MedDRA v26.1 | Systematic Assessment |
| |
| Otitis media | Infections and infestations | MedDRA v26.1 | Systematic Assessment |
| |
| Pneumonia | Infections and infestations | MedDRA v26.1 | Systematic Assessment |
| |
| Rash pustular | Infections and infestations | MedDRA v26.1 | Systematic Assessment |
| |
| Rhinitis | Infections and infestations | MedDRA v26.1 | Systematic Assessment |
| |
| Fall | Injury, poisoning and procedural complications | MedDRA v26.1 | Systematic Assessment |
| |
| Procedural pain | Injury, poisoning and procedural complications | MedDRA v26.1 | Systematic Assessment |
| |
| Blood alkaline phosphatase increased | Investigations | MedDRA v26.1 | Systematic Assessment |
| |
| Blood creatinine increased | Investigations | MedDRA v26.1 | Systematic Assessment |
| |
| Weight increased | Investigations | MedDRA v26.1 | Systematic Assessment |
| |
| Hypoalbuminaemia | Metabolism and nutrition disorders | MedDRA v26.1 | Systematic Assessment |
| |
| Hyponatraemia | Metabolism and nutrition disorders | MedDRA v26.1 | Systematic Assessment |
| |
| Flank pain | Musculoskeletal and connective tissue disorders | MedDRA v26.1 | Systematic Assessment |
| |
| Muscular weakness | Musculoskeletal and connective tissue disorders | MedDRA v26.1 | Systematic Assessment |
| |
| Neck pain | Musculoskeletal and connective tissue disorders | MedDRA v26.1 | Systematic Assessment |
| |
| Neurotoxicity | Nervous system disorders | MedDRA v26.1 | Systematic Assessment |
| |
| Restless legs syndrome | Nervous system disorders | MedDRA v26.1 | Systematic Assessment |
| |
| Syncope | Nervous system disorders | MedDRA v26.1 | Systematic Assessment |
| |
| Haematuria | Renal and urinary disorders | MedDRA v26.1 | Systematic Assessment |
| |
| Nephrolithiasis | Renal and urinary disorders | MedDRA v26.1 | Systematic Assessment |
| |
| Pollakiuria | Renal and urinary disorders | MedDRA v26.1 | Systematic Assessment |
| |
| Pelvic pain | Reproductive system and breast disorders | MedDRA v26.1 | Systematic Assessment |
| |
| Vulvovaginal dryness | Reproductive system and breast disorders | MedDRA v26.1 | Systematic Assessment |
| |
| Dysphonia | Respiratory, thoracic and mediastinal disorders | MedDRA v26.1 | Systematic Assessment |
| |
| Dyspnoea exertional | Respiratory, thoracic and mediastinal disorders | MedDRA v26.1 | Systematic Assessment |
| |
| Nasal dryness | Respiratory, thoracic and mediastinal disorders | MedDRA v26.1 | Systematic Assessment |
| |
| Pulmonary embolism | Respiratory, thoracic and mediastinal disorders | MedDRA v26.1 | Systematic Assessment |
| |
| Rhinorrhoea | Respiratory, thoracic and mediastinal disorders | MedDRA v26.1 | Systematic Assessment |
| |
| Sinus pain | Respiratory, thoracic and mediastinal disorders | MedDRA v26.1 | Systematic Assessment |
| |
| Wheezing | Respiratory, thoracic and mediastinal disorders | MedDRA v26.1 | Systematic Assessment |
| |
| Ecchymosis | Skin and subcutaneous tissue disorders | MedDRA v26.1 | Systematic Assessment |
| |
| Erythema | Skin and subcutaneous tissue disorders | MedDRA v26.1 | Systematic Assessment |
| |
| Onychomadesis | Skin and subcutaneous tissue disorders | MedDRA v26.1 | Systematic Assessment |
| |
| Palmar-plantar erythrodysaesthesia syndrome | Skin and subcutaneous tissue disorders | MedDRA v26.1 | Systematic Assessment |
| |
| Rash | Skin and subcutaneous tissue disorders | MedDRA v26.1 | Systematic Assessment |
| |
| Rash pruritic | Skin and subcutaneous tissue disorders | MedDRA v26.1 | Systematic Assessment |
| |
| Urticaria | Skin and subcutaneous tissue disorders | MedDRA v26.1 | Systematic Assessment |
| |
| Lymphoedema | Vascular disorders | MedDRA v26.1 | Systematic Assessment |
| |
| Thrombosis | Vascular disorders | MedDRA v26.1 | Systematic Assessment |
| |
| Haematochezia | Gastrointestinal disorders | MedDRA v26.1 | Systematic Assessment |
| |
| Eructation | Gastrointestinal disorders | MedDRA v26.1 | Systematic Assessment |
| |
| Proctitis | Gastrointestinal disorders | MedDRA v26.1 | Systematic Assessment |
| |
| Salivary hypersecretion | Gastrointestinal disorders | MedDRA v26.1 | Systematic Assessment |
| |
| Toothache | Gastrointestinal disorders | MedDRA v26.1 | Systematic Assessment |
| |
| COVID-19 pneumonia | Infections and infestations | MedDRA v26.1 | Systematic Assessment |
| |
| Kidney infection | Infections and infestations | MedDRA v26.1 | Systematic Assessment |
| |
| Contusion | Injury, poisoning and procedural complications | MedDRA v26.1 | Systematic Assessment |
| |
| Hypocalcaemia | Metabolism and nutrition disorders | MedDRA v26.1 | Systematic Assessment |
| |
| Arthritis | Musculoskeletal and connective tissue disorders | MedDRA v26.1 | Systematic Assessment |
| |
| Musculoskeletal stiffness | Musculoskeletal and connective tissue disorders | MedDRA v26.1 | Systematic Assessment |
| |
| Hemiparesis | Nervous system disorders | MedDRA v26.1 | Systematic Assessment |
| |
| Throat irritation | Respiratory, thoracic and mediastinal disorders | MedDRA v26.1 | Systematic Assessment |
| |
| Alopecia | Skin and subcutaneous tissue disorders | MedDRA v26.1 | Systematic Assessment |
| |
| Pain of skin | Skin and subcutaneous tissue disorders | MedDRA v26.1 | Systematic Assessment |
| |
| Breast pain | Reproductive system and breast disorders | MedDRA v26.1 | Systematic Assessment |
| |
| Vaginal haemorrhage | Reproductive system and breast disorders | MedDRA v26.1 | Systematic Assessment |
| |
| Pregnancy of partner | Social circumstances | MedDRA v26.1 | Systematic Assessment |
| |
| Cholecystitis | Hepatobiliary disorders | MedDRA v26.1 | Systematic Assessment |
| |
| Hepatic pain | Hepatobiliary disorders | MedDRA v26.1 | Systematic Assessment |
|
Not provided
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Chief Medical Officer | Seagen Inc. | (855) 473-2436 | medinfo@seagen.com |
| Prot_002.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan: Statistical Analysis Plan | May 11, 2022 | Jan 27, 2023 | SAP_001.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan: Addendum | Oct 23, 2023 | Oct 31, 2024 | SAP_003.pdf |
Not provided
| ID | Term |
|---|---|
| D015179 | Colorectal Neoplasms |
| ID | Term |
|---|---|
| D007414 | Intestinal Neoplasms |
| D005770 | Gastrointestinal Neoplasms |
| D004067 | Digestive System Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D004066 | Digestive System Diseases |
| D005767 | Gastrointestinal Diseases |
| D003108 | Colonic Diseases |
| D007410 | Intestinal Diseases |
| D012002 | Rectal Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| D000068878 | Trastuzumab |
| C000705452 | tucatinib |
| ID | Term |
|---|---|
| D061067 | Antibodies, Monoclonal, Humanized |
| D000911 | Antibodies, Monoclonal |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
| D007162 | Immunoproteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |
Not provided
Not provided
| Male |
|
| Not Hispanic or Latino |
|
| Unknown or Not Reported |
|
| Asian |
|
| Native Hawaiian or Other Pacific Islander |
|
| Black or African American |
|
| White |
|
| More than one race |
|
| Unknown or Not Reported |
|
| Grade 1 |
|
| Grade 2 |
|
| Europe |
|
|
|
| OG001 | Tucatinib Pre-Crossover (Cohort C) | Participants received Tucatinib 300 mg PO BID on Days 1 to 21 of each 21-day cycle. Participants who did not respond to monotherapy were given the option to receive tucatinib and trastuzumab based on radiographic progression (as determined by investigator assessment using RECIST v1.1), or if they had not achieved a PR or CR by the week 12 assessment. |
|
|
| Participants |
|
|
|
| OG001 |
| Tucatinib Pre-Crossover (Cohort C) |
Participants received Tucatinib 300 mg PO BID on Days 1 to 21 of each 21-day cycle. Participants who did not respond to monotherapy were given the option to receive tucatinib and trastuzumab based on radiographic progression (as determined by investigator assessment using RECIST v1.1), or if they had not achieved a PR or CR by the week 12 assessment. |
|
|
Participants received 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 until PD, death, withdrawal of consent, study closure, or alternative therapy. |
|
|
|
|
|
|
|
|
|
|
Participants received Tucatinib 300 mg PO BID on Days 1 to 21 of each 21-day cycle. Participants who did not respond to monotherapy were given the option to receive tucatinib and trastuzumab based on radiographic progression (as determined by investigator assessment using RECIST v1.1), or if they had not achieved a PR or CR by the week 12 assessment.
|
|
| OG001 | Tucatinib Post-Crossover (Cohort C) | Participants received 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 until PD, death, withdrawal of consent, study closure, or alternative therapy. |
|
|
|
|