Clinical Trials /

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

NCT04579380

Description:

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.

Related Conditions:
  • Biliary Tract Carcinoma
  • Breast Carcinoma
  • Cervical Carcinoma
  • Malignant Solid Tumor
  • Malignant Uterine Neoplasm
  • Non-Squamous Non-Small Cell Lung Carcinoma
  • Urothelial Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Basket Study of Tucatinib and Trastuzumab in Solid Tumors With HER2 Alterations
  • Official Title: A Phase 2 Basket Study of Tucatinib in Combination With Trastuzumab in Subjects With Previously Treated, Locally Advanced Unresectable or Metastatic Solid Tumors Driven by HER2 Alterations

Clinical Trial IDs

  • ORG STUDY ID: SGNTUC-019
  • NCT ID: NCT04579380

Conditions

  • Uterine Neoplasms
  • Uterine Cervical Neoplasms
  • Biliary Tract Neoplasms
  • Urologic Neoplasms
  • Carcinoma, Non-Small-Cell Lung
  • Breast Neoplasms

Interventions

DrugSynonymsArms
tucatinibTUKYSA, ARRY-380, ONT-380Tucatinib + Trastuzumab (+ Fulvestrant)
trastuzumabHerceptinTucatinib + Trastuzumab (+ Fulvestrant)
fulvestrantFaslodexTucatinib + Trastuzumab (+ Fulvestrant)

Purpose

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, GEC, and CRC) or HER2-mutated solid tumor types.
    

Trial Arms

NameTypeDescriptionInterventions
Tucatinib + Trastuzumab (+ Fulvestrant)ExperimentalTucatinib + trastuzumab (+ fulvestrant in hormone-receptor positive HER2-mutant breast cancer only)
  • tucatinib
  • trastuzumab
  • fulvestrant

Eligibility Criteria

        Inclusion Criteria

          -  Histologically or cytologically confirmed diagnosis of locally-advanced unresectable
             or metastatic solid tumor, including primary brain tumors

          -  Participants with disease types other than breast cancer, biliary tract cancer,
             non-squamous NSCLC, and cervical cancer: Disease progression on or after the most
             recent systemic therapy for locally-advanced unresectable or metastatic disease

          -  Participants with any breast cancer subtype:

               -  Must have HER2-mutated disease which does not display HER2
                  overexpression/amplification

               -  Must have progressed on or after ≥1 prior line of treatment (chemotherapy,
                  endocrine therapy, or targeted therapy) for locally-advanced unresectable or
                  metastatic breast cancer

               -  Participants with metastatic HR+ HER2-mutated disease must have received a prior
                  CDK4/6 inhibitor in the metastatic setting.

          -  Participants with biliary tract cancer: must have completed ≥1 prior line of treatment
             (chemotherapy, endocrine therapy, or targeted therapy)

          -  Participants with non-squamous NSCLC: has relapsed from or is refractory to standard
             treatment or for which no standard treatment is available

          -  Participants with cervical cancer:

               -  Participants with metastatic cervical cancer must have progressed on or after ≥1
                  prior line of systemic therapy in the metastatic setting.

               -  Participants with locally advanced unresectable cervical cancer must have
                  progressed on or after ≥1 prior lines 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, GEC, or CRC whose disease shows HER2
             amplification/overexpression.

          -  Previous treatment with HER2-directed therapy; participants with uterine serous
             carcinoma 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, 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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Confirmed objective response rate (cORR) per investigator assessment
Time Frame:From start of treatment up to approximately 2 years
Safety Issue:
Description:cORR is defined as the proportion of participants with best overall response of confirmed complete response (CR) or confirmed partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1

Secondary Outcome Measures

Measure:Disease control rate (DCR) per investigator assessment
Time Frame:From start of treatment up to approximately 2 years
Safety Issue:
Description:DCR is defined as the proportion of participants with confirmed CR, confirmed PR, or stable disease according to RECIST v1.1
Measure:Duration of response (DOR) per investigator assessment
Time Frame:From start of treatment up to approximately 2 years
Safety Issue:
Description:DOR is defined as the time from first documentation of objective response of confirmed CR or confirmed PR to the first documentation of disease progression per RECIST v1.1 or death from any cause, whichever occurs first.
Measure:Progression-free survival (PFS) per investigator assessment
Time Frame:From start of treatment up to approximately 2 years
Safety Issue:
Description:PFS is defined as the time from the date of treatment initiation to the date of disease progression according to RECIST v1.1 or death from any cause, whichever occurs first.
Measure:Overall survival (OS)
Time Frame:From start of treatment up to approximately 4 years
Safety Issue:
Description:OS is defined as the time from treatlemt initiation to death due to any cause.
Measure:Incidence of adverse events (AEs)
Time Frame:From start of treatment up to approximately 2 years
Safety Issue:
Description:
Measure:Incidence of laboratory abnormalities
Time Frame:From start of treatment up to approximately 2 years
Safety Issue:
Description:
Measure:Incidence of dose alterations
Time Frame:From start of treatment up to approximately 2 years
Safety Issue:
Description:

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Seagen Inc.

Trial Keywords

  • Cervical cancer
  • Uterine cancer
  • Biliary tract cancer
  • Gallbladder cancer
  • Cholangiocarcinoma
  • Urothelial cancer
  • Non-squamous non-small cell lung cancer
  • Non-squamous NSCLC
  • Breast cancer
  • Colorectal cancer
  • Ampullary cancer
  • Solid tumors
  • Solid tumors harboring somatic HER2 mutations
  • Seattle Genetics

Last Updated

April 13, 2021