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

Sponsor
Seagen Inc. (Industry)
Overall Status
Recruiting
CT.gov ID
NCT04579380
Collaborator
(none)
270
64
1
52.6
4.2
0.1

Study Details

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.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
270 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
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
Actual Study Start Date :
Jan 11, 2021
Anticipated Primary Completion Date :
Jan 31, 2023
Anticipated Study Completion Date :
May 31, 2025

Arms and Interventions

Arm Intervention/Treatment
Experimental: Tucatinib + Trastuzumab (+ Fulvestrant)

Tucatinib + trastuzumab (+ fulvestrant in hormone-receptor positive HER2-mutant breast cancer only)

Drug: tucatinib
300 mg orally twice daily
Other Names:
  • TUKYSA, ARRY-380, ONT-380
  • Drug: trastuzumab
    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
    Other Names:
  • Herceptin
  • Drug: fulvestrant
    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.
    Other Names:
  • Faslodex
  • Outcome Measures

    Primary Outcome Measures

    1. Confirmed objective response rate (cORR) per investigator assessment [From start of treatment up to approximately 2 years]

      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

    1. Disease control rate (DCR) per investigator assessment [From start of treatment up to approximately 2 years]

      DCR is defined as the proportion of participants with confirmed CR, confirmed PR, or stable disease according to RECIST v1.1

    2. Duration of response (DOR) per investigator assessment [From start of treatment up to approximately 2 years]

      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.

    3. Progression-free survival (PFS) per investigator assessment [From start of treatment up to approximately 2 years]

      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.

    4. Overall survival (OS) [From start of treatment up to approximately 4 years]

      OS is defined as the time from treatment initiation to death due to any cause.

    5. Incidence of adverse events (AEs) [From start of treatment up to approximately 2 years]

      Any untoward medical occurrence in a clinical investigational participant administered a medicinal product and which does not necessarily have a causal relationship with this treatment.

    6. Incidence of laboratory abnormalities [From start of treatment up to approximately 2 years]

      To be summarized using descriptive statistics.

    7. Incidence of dose alterations [From start of treatment up to approximately 2 years]

    8. Maximum concentration (Cmax) [Approximately 4 months, during first 6 cycles of treatment]

      To be summarized using descriptive statistics.

    9. Trough concentration (Ctrough) [Approximately 4 months, during first 6 cycles of treatment]

      To be summarized using descriptive statistics.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No

    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.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Arizona Oncology Associates, PC - HAL Goodyear Arizona United States 85395
    2 HonorHealth Phoenix Arizona United States 85016
    3 Mayo Clinic Arizona Phoenix Arizona United States 85054
    4 Arizona Cancer Center / University of Arizona Tucson Arizona United States 85724-5024
    5 UC San Diego / Moores Cancer Center La Jolla California United States 92093
    6 Pacific Shores Medical Group Long Beach California United States 90813
    7 Rocky Mountain Cancer Centers Boulder Colorado United States 80303
    8 Regional Cancer Care Associates Manchester Connecticut United States 06040
    9 Lombardi Cancer Center / Georgetown University Medical Center Washington District of Columbia United States 20007
    10 Mayo Clinic Florida Jacksonville Florida United States 32224
    11 H. Lee Moffitt Cancer Center and Research Institute Tampa Florida United States 33612
    12 H. Lee Moffitt Cancer Center and Research Institute Tampa Florida United States 33612
    13 University Cancer & Blood Center, LLC Athens Georgia United States 30607
    14 Massachusetts General Hospital Boston Massachusetts United States 02114
    15 Mayo Clinic Rochester Rochester Minnesota United States 55905
    16 HealthPartners Institute Saint Louis Park Minnesota United States 55416
    17 Washington University in St Louis Saint Louis Missouri United States 63108
    18 Nebraska Cancer Specialists Omaha Nebraska United States 68130
    19 NYU Langone Hospital Mineola New York United States 11501
    20 NYU Langone Hospital New York New York United States 10016
    21 Mount Sinai Medical Center New York New York United States 10029
    22 Duke University Medical Center Durham North Carolina United States 27710
    23 Case Western Reserve University / University Hospitals Cleveland Medical Center Cleveland Ohio United States 44106
    24 James Cancer Hospital / Ohio State University Columbus Ohio United States 43210
    25 University of Pittsburgh Medical Center (UPMC)/Hillman Cancer Center Pittsburgh Pennsylvania United States 15213
    26 Prisma Health Greenville South Carolina United States 29605
    27 Tennessee Oncology-Nashville/Sarah Cannon Research Institute Nashville Tennessee United States 37203
    28 Texas Oncology - West Texas Abilene Texas United States 79606
    29 Texas Oncology, P.A. - Dallas Dallas Texas United States 75246
    30 US Oncology Central Regulatory The Woodlands Texas United States 77380
    31 Texas Oncology - Waco Waco Texas United States 76712
    32 Huntsman Cancer Institute/University of Utah Salt Lake City Utah United States 84112
    33 Virginia Cancer Specialists, PC Fairfax Virginia United States 22031
    34 Seattle Cancer Care Alliance / University of Washington Seattle Washington United States 98109-1023
    35 Northwest Cancer Specialists, P.C. Vancouver Washington United States 98684
    36 Carbone Cancer Center / University of Wisconsin Madison Wisconsin United States 53792
    37 Cliniques Universitaires Saint Luc Brussels Other Belgium 1200
    38 Grand Hopital de Charleroi Charleroi Other Belgium 6000
    39 Universitair Ziekenhuis Antwerpen Edegem Other Belgium 2650
    40 Academisch Ziekenhuis Groeninge Kortrijk Other Belgium 8500
    41 CHU de Liege Liege Other Belgium 4000
    42 Istituto Europeo di Oncologia Milano Other Italy 20141
    43 Azienda Socio Sanitaria Territoriale di Monza. Ospedale San Gerardo Monza Other Italy 20900
    44 National Cancer Center Hospital Chuo-ku Other Japan 104-0045
    45 National Cancer Center Hospital East Kashiwa-shi Other Japan 277-8577
    46 St. Marianna University School of Medicine Kawasaki-shi Other Japan 2168511
    47 Aichi Cancer Center Nagoya-shi Other Japan 464-8681
    48 Kindai University Hospital Osakasayama Other Japan 589-8511
    49 The Cancer Institute Hospital of JFCR Tokyo Other Japan 135-8550
    50 Seoul National University Bundang Hospital Seongnam-si Other Korea, Republic of 13620
    51 Seoul National University Hospital Seoul Other Korea, Republic of 03080
    52 Samsung Medical Center Seoul Other Korea, Republic of 06351
    53 Severance Hospital, Yonsei University Health System Seoul Other Korea, Republic of 120-752
    54 Seoul National University Boramae Medical Center Seoul Other Korea, Republic of
    55 Netherlands Cancer Institute Amsterdam Other Netherlands 1066 WX
    56 Med Polonia Sp. z o. o. Poznan Other Poland 60-693
    57 Hospital Universitario Vall d'Hebron Barcelona Other Spain 08035
    58 L'Institut Catala d'Oncologia L'Hospitalet de Llobregat Other Spain 08908
    59 Hospital Universitario 12 de Octubre Madrid Other Spain 28041
    60 Hospital Clinico Universitario de Santiago de Compostela Santiago de Compostela Other Spain 15706
    61 Hospital Clinico Universitario de Valencia Valencia Other Spain 46010
    62 The Royal Marsden Hospital London Other United Kingdom SW3 6JJ
    63 Sarah Cannon Research Institute UK London Other United Kingdom W1G 6AD
    64 The Royal Marsden Hospital (Surrey) Sutton Other United Kingdom SM2 5PT

    Sponsors and Collaborators

    • Seagen Inc.

    Investigators

    • Study Director: Jorge Ramos, DO, Seagen Inc.

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Seagen Inc.
    ClinicalTrials.gov Identifier:
    NCT04579380
    Other Study ID Numbers:
    • SGNTUC-019
    First Posted:
    Oct 8, 2020
    Last Update Posted:
    Aug 17, 2022
    Last Verified:
    Aug 1, 2022

    Study Results

    No Results Posted as of Aug 17, 2022