TriangleNCT03043313 · CITED IN SOURCE DOCUMENTS
Tucatinib Plus Trastuzumab in Patients With HER2+ Colorectal Cancer
An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.
- Phase
- PHASE2
- Status at capture
- COMPLETED
- Registry last update
- 2024-11-26
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.
Open the original ClinicalTrials.gov record → · Download preserved record
What did the study report?
Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.
Participant flow
Baseline characteristics
Confirmed Objective Response Rate (cORR) Per RECIST v1.1 Per Blinded Independent Central Review (BICR) in Pooled Cohorts A+B
ORR by 12 Weeks of Treatment Per RECIST v1.1 According to BICR Assessment
Duration of Response (DOR) Per RECIST v1.1 According to BICR Assessment
Progression-Free Survival (PFS) Per RECIST v1.1 According to BICR Assessment for Pooled Cohorts A+B
Overall Survival (OS) in Pooled Cohorts A+B
Number of Participants With Adverse Events (AEs): Interim Analysis
Number of Participants With AEs: Final Analysis
Number of Participants With AEs Resulting in Dose Modification: Interim Analysis
Number of Participants With AEs Resulting in Dose Modification: Final Analysis
Number of Participants With Treatment-Emergent Laboratory Abnormalities (Hematology): Interim Analysis
Number of Participants With Treatment-Emergent Laboratory Abnormalities (Hematology): Final Analysis
Number of Participants With Treatment-Emergent Laboratory Abnormalities (Chemistry): Interim Analysis
Number of Participants With Treatment-Emergent Laboratory Abnormalities (Chemistry): Final Analysis
Number of Participants With Clinically Significant Vital Signs: Final Analysis
Adverse events
Limitations, agreements, and source contact
Who could take part
- eligibility Criteria
- 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: * HER2+ overexpression (3+ immunohistochemistry \[IHC\]) by an FDA-approved or Conformité Européene (CE)-marked HER2 ICH test * HER2 2+ IHC is eligible if the tumor is amplified by an FDA-approved or CE-marked HER2 in situ hybridization assay (FISH or chromogenic in situ hybridization \[CISH\])) * HER2 (ERBB2) amplification by CLIA-certified or ISO-accredited next generation sequencing (NGS) sequencing assay * 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: * Alopecia and neuropathy, which must have resolved to ≤ Grade 2 * Congestive heart failure (CHF), which must have been ≤ Grade 1 in severity at the time of occurrence, and must have resolved completely * Anemia, which must have resolved to ≤ Grade 2 * Decreased ANC, which must have resolved to ≤ Grade 2 * 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 * Exception for participants with a documented sustained virologic response of 12 weeks * 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. * Exceptions are malignancies with a negligible risk of metastasis or death * Subjects with known active CNS metastasis * Irradiated or resected lesions are permitted, provided the lesions are fully treated and inactive, subject is asymptomatic, and no steroids have been administered for at least 30 days
- healthy Volunteers
- false
- minimum Age
- 18 Years
- sex
- ALL
- std Ages
- ADULT
- OLDER_ADULT
Treatment arms and interventions
- arm Groups
- description
- 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.
- intervention Names
- Drug: Trastuzumab
- Drug: Tucatinib
- label
- Cohort A: Tucatinib + Trastuzumab
- type
- EXPERIMENTAL
- description
- 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.
- intervention Names
- Drug: Trastuzumab
- Drug: Tucatinib
- label
- Cohort B: Tucatinib + Trastuzumab
- type
- EXPERIMENTAL
- description
- 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.
- intervention Names
- Drug: Tucatinib
- label
- Cohort C: Tucatinib Monotherapy
- type
- EXPERIMENTAL
- interventions
- arm Group Labels
- Cohort A: Tucatinib + Trastuzumab
- Cohort B: Tucatinib + Trastuzumab
- description
- Given intravenously (into the vein; IV)
- name
- Trastuzumab
- other Names
- Herceptin
- type
- DRUG
- arm Group Labels
- Cohort A: Tucatinib + Trastuzumab
- Cohort B: Tucatinib + Trastuzumab
- Cohort C: Tucatinib Monotherapy
- description
- Given orally
- name
- Tucatinib
- other Names
- ARRY-380
- ONT-380
- TUKYSA
- type
- DRUG
Study design
- allocation
- RANDOMIZED
- intervention Model
- PARALLEL
- masking Info
- masking
- NONE
- primary Purpose
- TREATMENT
Enrollment
- count
- 117
- type
- ACTUAL
Registered outcome plans (not posted results)
- primary Outcomes
- description
- 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.
- measure
- Confirmed Objective Response Rate (cORR) Per RECIST v1.1 Per Blinded Independent Central Review (BICR) in Pooled Cohorts A+B
- time Frame
- Up to 46.6 months
- secondary Outcomes
- description
- 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.
- measure
- ORR by 12 Weeks of Treatment Per RECIST v1.1 According to BICR Assessment
- time Frame
- Up to 3 months
- description
- 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.
- measure
- Duration of Response (DOR) Per RECIST v1.1 According to BICR Assessment
- time Frame
- Up to 64.1 months
- description
- 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.
- measure
- Progression-Free Survival (PFS) Per RECIST v1.1 According to BICR Assessment for Pooled Cohorts A+B
- time Frame
- Up to 64.1 months
- description
- 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.
- measure
- Overall Survival (OS) in Pooled Cohorts A+B
- time Frame
- Up to 71.8 months
- description
- 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.
- measure
- Number of Participants With Adverse Events (AEs): Interim Analysis
- time Frame
- Up to 49.3 months
- description
- 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.
- measure
- Number of Participants With AEs: Final Analysis
- time Frame
- Up to 65.1 months
- 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.
- measure
- Number of Participants With AEs Resulting in Dose Modification: Interim Analysis
- time Frame
- Up to 49.3 months
- 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. Drug interruption included infusion interrupted (full dose received within 24hrs).
- measure
- Number of Participants With AEs Resulting in Dose Modification: Final Analysis
- time Frame
- Up to 65.1 months
- description
- 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.
- measure
- Number of Participants With Treatment-Emergent Laboratory Abnormalities (Hematology): Interim Analysis
- time Frame
- Up to 49.3 months
- description
- 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.
- measure
- Number of Participants With Treatment-Emergent Laboratory Abnormalities (Hematology): Final Analysis
- time Frame
- Up to 65.1 months
- description
- 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.
- measure
- Number of Participants With Treatment-Emergent Laboratory Abnormalities (Chemistry): Interim Analysis
- time Frame
- Up to 49.3 months
- description
- 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.
- measure
- Number of Participants With Treatment-Emergent Laboratory Abnormalities (Chemistry): Final Analysis
- time Frame
- Up to 65.1 months
Full study description
- brief Summary
- 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.
Source references
- references
- citation
- 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.
- pmid
- 39368039
- type
- DERIVED
- citation
- 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.
- pmid
- 37941353
- type
- DERIVED
- citation
- 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.
- pmid
- 37318379
- type
- DERIVED
- citation
- 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.
- pmid
- 37142372
- type
- DERIVED
Source notices and limitations
Discovery and provenance
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- 1 figure 2 14.2 HER2-Positive Metastatic Colorectal Cancer The efficacy of TUKYSA in combination with trastuzumab was evaluated in 84 patients in MOUNTAINEER (NCT03043313), an open-label, multicenter trial. Patients were required to have HER2-positive, RAS wild-type, unresectable or metastatic colorectal cancer and prior treatme
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Preserved source evidence · Not medical advice