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NCT04579380 · CITED IN SOURCE DOCUMENTS

Basket Study of Tucatinib and Trastuzumab in Solid Tumors With HER2 Alterations

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
ACTIVE NOT RECRUITING
Registry last update
2026-08-21

This trial studies how well tucatinib works for solid tumors that make either more HER2 or a different type of HER2 than usual (HER2 alterations) The solid tumors studied in this trial have either spread to other parts of the body (metastatic) or cannot be removed completely with surgery (unresectable). All participants will get both tucatinib and trastuzumab. People with hormone-receptor positive breast cancer will also get a drug called fulvestrant. The trial will also look at what side effects happen. A side effect is anything a drug does besides treating cancer.

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.

flow

Participant flow

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baseline

Baseline characteristics

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outcome · POSTED

Confirmed Objective Response Rate (cORR) as Assessed by Investigator

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outcome · NOT POSTED

Confirmed Disease Control Rate (DCR) as Assessed by Investigator

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outcome · NOT POSTED

Duration of Response (DOR) as Assessed by Investigator

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outcome · NOT POSTED

Progression-Free Survival (PFS) as Assessed by Investigator

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outcome · NOT POSTED

Overall Survival (OS)

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outcome · NOT POSTED

Number of Participants With Treatment Emergent Adverse Events (TEAEs)

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outcome · NOT POSTED

Number of Participants With Treatment Emergent Laboratory Test Abnormalities

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outcome · NOT POSTED

Number of Participants With Any Dose Modifications Due to AEs

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outcome · NOT POSTED

Number of Participants With TEAEs of Special Interest

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outcome · POSTED

Maximum Concentration (Cmax) of Tucatinib

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outcome · POSTED

Trough Concentration (Ctrough) of Tucatinib

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adverse events

Adverse events

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more info

Limitations, agreements, and source contact

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Who could take part
eligibility Criteria
Inclusion Criteria * Histologically or cytologically confirmed diagnosis of locally-advanced unresectable or metastatic solid tumor, including primary brain tumors * Participants with non-squamous NSCLC must have progressed during or after standard treatment or for which no standard treatment is available * Participants with other disease types must have progressed during or after ≥1 prior line of systemic therapy for locally-advanced unresectable or metastatic disease * Disease progression during or after, or intolerance of, the most recent line of systemic therapy * Disease demonstrating HER2 alterations (overexpression/amplification or HER2 activating mutations), as determined by local or central testing processed in a Clinical Laboratory Improvement Amendments (CLIA)- or International Organization for Standardization (ISO) accredited laboratory, according to one of the following: * HER2 overexpression/amplification from fresh or archival tumor tissue or blood * Known activating HER2 mutations detected in fresh or archival tumor tissue or blood * Have measurable disease per RECIST v1.1 criteria according to investigator assessment * Have Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 Exclusion Criteria * Participants with breast cancer, gastric or gastroesophageal junction adenocarcinoma, or CRC whose disease shows HER2 amplification/overexpression. * Previous treatment with HER2-directed therapy; participants with uterine serous carcinoma or HER2-mutated gastric or gastroesophageal junction adenocarcinoma without HER2-overexpression/amplification may have received prior trastuzumab * Known hypersensitivity to any component of the drug formulation of tucatinib or trastuzumab (drug substance, excipients, murine proteins), or any component of the drug formulation of fulvestrant in participants with HR+ HER2-mutated breast cancer * History of exposure to a 360 mg/m² doxorubicin-equivalent or \>720 mg/m\^2 epirubicin-equivalent cumulative dose of anthracyclines * Treatment with any systemic anti-cancer therapy, radiation therapy, major surgery, or experimental agent within ≤3 weeks of first dose of study treatment or are currently participating in another interventional clinical trial. There are additional inclusion and exclusion criteria. The study center will determine if criteria for participation are met.
healthy Volunteers
false
minimum Age
18 Years
sex
ALL
std Ages
  1. ADULT
  2. OLDER_ADULT
Treatment arms and interventions
arm Groups
  1. description
    Tucatinib + trastuzumab (+ fulvestrant in hormone-receptor positive HER2-mutant breast cancer only)
    intervention Names
    1. Drug: tucatinib
    2. Drug: trastuzumab
    3. Drug: fulvestrant
    label
    Tucatinib + Trastuzumab (+ Fulvestrant)
    type
    EXPERIMENTAL
interventions
  1. arm Group Labels
    1. Tucatinib + Trastuzumab (+ Fulvestrant)
    description
    300 mg orally twice daily
    name
    tucatinib
    other Names
    1. TUKYSA, ARRY-380, ONT-380
    type
    DRUG
  2. arm Group Labels
    1. Tucatinib + Trastuzumab (+ Fulvestrant)
    description
    Given into the vein (intravenously; IV). 8mg/kg IV on Cycle 1 Day 1, and 6mg/kg every 21 days starting on Cycle 2 Day 1
    name
    trastuzumab
    other Names
    1. Herceptin
    type
    DRUG
  3. arm Group Labels
    1. Tucatinib + Trastuzumab (+ Fulvestrant)
    description
    Given into the muscle (intramuscular; IM) once every 4 weeks starting from Cycle 1 Day 1, plus one dose on Cycle 1 Day 15. Only administered to participants with hormone-receptor positive breast cancer.
    name
    fulvestrant
    other Names
    1. Faslodex
    type
    DRUG
Study design
allocation
NA
intervention Model
SINGLE_GROUP
masking Info
masking
NONE
primary Purpose
TREATMENT
Enrollment
count
217
type
ACTUAL
Registered outcome plans (not posted results)
primary Outcomes
  1. description
    Confirmed ORR was defined as the percentage of participants with best overall response of complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria version (v)1.1 as assessed by investigator and was considered as confirmed when subsequent response was at least 4 weeks after initial response. As per RECIST v1.1, CR: disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (\<)10 millimeter (mm). PR: at least a greater than or equal to (\>=)30 % decrease in the sum of diameters (SOD) of target lesions (longest for non-nodal target lesions and the short axes for nodal target lesions), taking as reference the baseline sum diameters. Disease progression (PD): at least \>=20% relative increase in SOD of target lesion taking as reference the smallest sum on study (including baseline sum if that is the smallest on study).
    measure
    Confirmed Objective Response Rate (cORR) as Assessed by Investigator
    time Frame
    From the first dose of study treatment until the first documented CR or PR on or before the first documented PD or new anti-cancer therapies or death, whichever occurred first (up to 28.3 months)
secondary Outcomes
  1. description
    DCR was defined as the percentage of participants with confirmed CR, PR, or stable disease (SD or non-CR/non-PD) according to RECIST v1.1 as assessed by investigator. As per RECIST v1.1, CR: disappearance of all target (T) lesions and non-target (NT) lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. PR: at least \>=30 % decrease in the SOD of target lesions (longest for non-nodal target lesions and the short axes for nodal target lesions), taking as reference the baseline sum diameters. PD: at least \>=20% relative increase in SOD of target lesions taking as reference the smallest sum on study (including baseline sum if that is the smallest on study). SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest SOD while on study and cannot have met criteria for PD previously.
    measure
    Confirmed Disease Control Rate (DCR) as Assessed by Investigator
    time Frame
    From the first dose study treatment until PD or death, whichever occurred first (approximately 52.7 months)
  2. description
    DOR: time from first documentation of confirmed CR/PR to first documentation of PD according to RECIST v1.1 or death from any cause, whichever occurred earlier. Per RECIST v1.1, CR: disappearance of all T/NT lesions(L). Any pathological lymph nodes (whether T/NT) must have reduction in short axis to \<10 mm. PR: at least \>=30 % decrease in SOD of TL, taking reference baseline sum diameters. PD: at least \>=20% relative increase in SOD of TL taking reference smallest sum on study. Participants who do not have PD \& were still on study at time of an analysis/ who have started new anticancer treatment/discontinue prior to documentation of PD were censored at date of last adequate response assessment documenting absence of PD. Participants who had PD/death occurred after two/more consecutive missing scheduled response assessments were censored at date of last adequate response assessment of CR, PR, SD,/non-CR/non-PD. Kaplan-Meier method was used for evaluation.
    measure
    Duration of Response (DOR) as Assessed by Investigator
    time Frame
    From the first documented CR or PR until the first documentation of PD or death or censoring date, whichever occurred first (approximately 52.7 months)
  3. description
    PFS was defined as time from the date of treatment initiation to date of PD as per RECIST v1.1 or death from any cause, whichever occurred first . As per RECIST v1.1, PD: least \>=20% relative increase in SOD of target lesions taking as reference the smallest sum on study (including baseline sum if that is smallest on study). Participants who do not have PD and were still on study at time of an analysis/ who have started new anticancer treatment/discontinue prior to documentation of PD were censored at date of last adequate response assessment documenting absence of PD. Participants who had PD or death occurred after two or more consecutive missing scheduled response assessments were censored at date of last adequate response assessment of CR, PR, SD,/non-CR/non-PD. Kaplan-Meier method was used for evaluation.
    measure
    Progression-Free Survival (PFS) as Assessed by Investigator
    time Frame
    From the first documented CR or PR until the first documentation of PD or death or censoring date, whichever occurred first (approximately 52.7 months)
  4. description
    OS was defined as the time from treatment initiation to death due to any cause. For a participant who was not known to have died by the end of study follow-up, observation of OS was censored on the date the participant was last known to be alive (i.e., the date of last contact). Participants lacking data beyond the day of treatment initiation were censored on the date of treatment initiation (i.e., OS duration of 1 day). Kaplan-Meier method was used for evaluation.
    measure
    Overall Survival (OS)
    time Frame
    From date of start of study treatment until date of death or censoring date (approximately 52.7 months)
  5. description
    An AE was any untoward medical occurrence in a participant or clinical investigational participant administered a medicinal product and which did not necessarily have a causal relationship with this treatment. A TEAE was defined as a newly occurring or worsening AE after the first dose of study treatment.
    measure
    Number of Participants With Treatment Emergent Adverse Events (TEAEs)
    time Frame
    From first dose of the study treatment (Day 1) up to 30 days after the last dose of study treatment (approximately 52.7 months)
  6. description
    Treatment-emergent laboratory abnormalities were defined as abnormalities that are new or worsened on or after receiving the first dose of study treatment up to 30 days after the last dose of study treatment. The following laboratory abnormalities were assessed: A-) Hematology: hemoglobin decreased, leukocytes decreased, lymphocytes decreased and increased, neutrophils decreased and platelets decreased; B-) Chemistry: alanine aminotransferase increased, albumin decreased, alkaline phosphatase increased, aspartate aminotransferase increased, calcium corrected for albumin decreased and increased, creatinine increased, glomerular filtration rate estimated decreased, glucose decreased, lactate dehydrogenase increased, magnesium increased and decreased, potassium increased and decreased, sodium increased and decreased and total bilirubin increased.
    measure
    Number of Participants With Treatment Emergent Laboratory Test Abnormalities
    time Frame
    From first dose of the study treatment (Day 1) up to 30 days after the last dose of study treatment (approximately 52.7 months)
  7. description
    Dose modification included dose hold, dose reduction, or discontinuation of drugs. Dose reductions or treatment interruption/discontinuation were made at the discretion of the investigator.
    measure
    Number of Participants With Any Dose Modifications Due to AEs
    time Frame
    From first dose of the study treatment (Day 1) up to the last dose of study treatment (approximately 52.7 months)
  8. description
    An adverse event of special interest (AESI) were any serious or nonserious AE that were of scientific or medical concern as defined by the sponsor and specific to the program, for which ongoing monitoring and rapid communication to the sponsor were appropriate. A TEAE was defined as a newly occurring or worsening AE after the first dose of study treatment (tucatinib, trastuzumab or fulvestrant). AESIs for this study were related to hepatoxicity.
    measure
    Number of Participants With TEAEs of Special Interest
    time Frame
    From first dose of the study treatment (Day 1) up to the last dose of study treatment (approximately 52.7 months)
  9. measure
    Maximum Concentration (Cmax) of Tucatinib
    time Frame
    Cycle 3 Day 1: anytime within 1-4 hours post-dose
  10. measure
    Trough Concentration (Ctrough) of Tucatinib
    time Frame
    Cycle 3 Day 1: Predose
Full study description
brief Summary
This trial studies how well tucatinib works for solid tumors that make either more HER2 or a different type of HER2 than usual (HER2 alterations) The solid tumors studied in this trial have either spread to other parts of the body (metastatic) or cannot be removed completely with surgery (unresectable). All participants will get both tucatinib and trastuzumab. People with hormone-receptor positive breast cancer will also get a drug called fulvestrant. The trial will also look at what side effects happen. A side effect is anything a drug does besides treating cancer.
detailed Description
There are multiple cohorts in this trial: * 5 tumor specific cohorts with HER2 overexpression/amplification (cervical cancer, uterine cancer, biliary tract cancer, urothelial cancer, and non-squamous non-small cell lung cancer \[NSCLC\]) * 2 tumor specific cohorts with HER2 mutations (non-squamous NSCLC and breast cancer) * 2 cohorts which will enroll all other HER2 amplified/overexpressed solid tumor types (except breast cancer, gastric or gastroesophageal junction adenocarcinoma \[GEC\], and colorectal cancer \[CRC\]) or HER2-mutated solid tumor types.
Source references
references
  1. citation
    Okines AFC, Curigliano G, Mizuno N, Oh DY, Rorive A, Soliman H, Takahashi S, Bekaii-Saab T, Burkard ME, Chung KY, Debruyne PR, Fox JR, Gambardella V, Gil-Martin M, Hamilton EP, Monk BJ, Nakamura Y, Nguyen D, O'Malley DM, Olawaiye AB, Pothuri B, Reck M, Sudo K, Sunakawa Y, Van Marcke C, Yu EY, Ramos J, Tan S, Bieda M, Stinchcombe TE, Pohlmann PR. Tucatinib and trastuzumab in HER2-mutated metastatic breast cancer: a phase 2 basket trial. Nat Med. 2025 Mar;31(3):909-916. doi: 10.1038/s41591-024-03462-0. Epub 2025 Jan 17.
    pmid
    39825152
    type
    DERIVED
  2. citation
    Nakamura Y, Mizuno N, Sunakawa Y, Canon JL, Galsky MD, Hamilton E, Hayashi H, Jerusalem G, Kim ST, Lee KW, Kankeu Fonkoua LA, Monk BJ, Nguyen D, Oh DY, Okines A, O'Malley DM, Pohlmann P, Reck M, Shin SJ, Sudo K, Takahashi S, Van Marcke C, Yu EY, Groisberg R, Ramos J, Tan S, Stinchcombe TE, Bekaii-Saab T. Tucatinib and Trastuzumab for Previously Treated Human Epidermal Growth Factor Receptor 2-Positive Metastatic Biliary Tract Cancer (SGNTUC-019): A Phase II Basket Study. J Clin Oncol. 2023 Dec 20;41(36):5569-5578. doi: 10.1200/JCO.23.00606. Epub 2023 Sep 26.
    pmid
    37751561
    type
    DERIVED
Source notices and limitations
    Discovery and provenance
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        al activity in previously treated patients. </p> <div class="pdq-content-list"><ol id="_628"><li>The tumor-agnostic phase II <a href="/clinicaltrials/NCT04579380">SGNTUC-019</a> study (NCT04579380) evaluated the combination of tucatinib and trastuzumab. The trial included a cohort of 30 patients with previously treated
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        atients. </p> <div class="pdq-content-list"><ol id="_628"><li>The tumor-agnostic phase II <a href="/clinicaltrials/NCT04579380">SGNTUC-019</a> study (NCT04579380) evaluated the combination of tucatinib and trastuzumab. The trial included a cohort of 30 patients with previously treated HER2-overexpressing or HER2-amplifi
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      1. context
        Updated: March 28, 2025
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        display
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    Preserved source evidence · Not medical advice