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

November 16, 2023 updated by: Seagen Inc.

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

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.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Actual)

217

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Belgium
    • Other
      • Brussels, Other, Belgium, 1200
        • Cliniques Universitaires Saint Luc
      • Charleroi, Other, Belgium, 6000
        • Grand Hopital de Charleroi
      • Edegem, Other, Belgium, 2650
        • Universitair Ziekenhuis Antwerpen
      • Kortrijk, Other, Belgium, 8500
        • Academisch Ziekenhuis Groeninge
      • Liege, Other, Belgium, 4000
        • CHU de Liège
      • Mechelen, Other, Belgium, 2800
        • AZ Sint-Maarten
  • Germany
    • Other
      • Berlin, Other, Germany, 12203
        • Charite Universitatsmedizin Berlin
  • Italy
    • Other
      • Meldola, Other, Italy, 47014
        • IRCCS Istituto Romagnolo per lo Studio dei Tumori Dino Amadori- IRST S.r.l
      • Milano, Other, Italy, 20132
        • Istituto Europeo di Oncologia
      • Monza, Other, Italy, 20900
        • Fondazione IRCCS San Gerardo dei Tintori
  • Japan
    • Other
      • Chuo-Ku, Other, Japan, 104-0045
        • National Cancer Center Hospital
      • Kashiwa-shi, Other, Japan, 277-8577
        • National Cancer Center Hospital East
      • Kawasaki-shi, Other, Japan, 2168511
        • St. Marianna University School of Medicine
      • Nagoya-shi, Other, Japan, 464-8681
        • Aichi Cancer Center
      • Osakasayama, Other, Japan, 589-8511
        • Kindai University Hospital
      • Tokyo, Other, Japan, 81004
        • The Cancer Institute Hospital of JFCR
  • Korea, Republic of
    • Other
      • Seongnam-si, Other, Korea, Republic of, 13620
        • Seoul National University Bundang Hospital
      • Seoul, Other, Korea, Republic of, 03080
        • Seoul National University Hospital
      • Seoul, Other, Korea, Republic of, 06351
        • Samsung Medical Center
      • Seoul, Other, Korea, Republic of, 07671
        • Seoul National University Boramae Medical Center
      • Seoul, Other, Korea, Republic of, 120-752
        • Severance Hospital, Yonsei University Health System
  • Netherlands
    • Other
      • Amsterdam, Other, Netherlands, 1066 WX
        • Netherlands Cancer Institute
  • Poland
    • Other
      • Poznan, Other, Poland, 60-693
        • Med Polonia Sp. z o. o.
  • Spain
    • Other
      • Barcelona, Other, Spain, 08035
        • Hospital Universitario Vall d'Hebrón
      • L'Hospitalet de Llobregat, Other, Spain, 08908
        • L'Institut Catala d'Oncologia
      • Madrid, Other, Spain, 28041
        • Hospital Universitario 12 de Octubre
      • Santiago de Compostela, Other, Spain, 15706
        • Hospital Clínico Universitario de Santiago de Compostela
      • Valencia, Other, Spain, 46010
        • Hospital Clínico Universitario de Valencia
  • United Kingdom
      • London, United Kingdom, SE1 9RT
        • Guy's Hospital
    • Other
      • London, Other, United Kingdom, SW3 6JJ
        • The Royal Marsden Hospital
      • London, Other, United Kingdom, W1G 6AD
        • Sarah Cannon Research Institute UK
      • Sutton, Other, United Kingdom, SM2 5PT
        • The Royal Marsden Hospital (Surrey)
  • United States
    • Arizona
      • Goodyear, Arizona, United States, 85395
        • Arizona Oncology Associates, PC - HAL
      • Phoenix, Arizona, United States, 85054
        • Mayo Clinic Arizona
      • Phoenix, Arizona, United States, 85016
        • HonorHealth
      • Tucson, Arizona, United States, 85724
        • Arizona Cancer Center / University of Arizona
    • California
      • La Jolla, California, United States, 92093
        • UC San Diego / Moores Cancer Center
      • Long Beach, California, United States, 90813
        • Pacific Shores Medical Group
    • Colorado
      • Boulder, Colorado, United States, 80303
        • Rocky Mountain Cancer Centers
    • Connecticut
      • Manchester, Connecticut, United States, 06040
        • Regional Cancer Care Associates
    • District of Columbia
      • Washington, District of Columbia, United States, 20007
        • Lombardi Cancer Center / Georgetown University Medical Center
    • Florida
      • Jacksonville, Florida, United States, 32224
        • Mayo Clinic Florida
      • Tampa, Florida, United States, 33612
        • H. Lee Moffitt Cancer Center and Research Institute
    • Georgia
      • Athens, Georgia, United States, 30607
        • University Cancer & Blood Center, LLC
    • Massachusetts
      • Boston, Massachusetts, United States, 02114
        • Massachusetts General Hospital
    • Minnesota
      • Rochester, Minnesota, United States, 55905
        • Mayo Clinic Rochester
      • Saint Louis Park, Minnesota, United States, 55416
        • HealthPartners Institute
    • Missouri
      • Saint Louis, Missouri, United States, 63108
        • Washington University in St Louis
    • Nebraska
      • Omaha, Nebraska, United States, 68130
        • Nebraska Cancer Specialists
    • New York
      • Mineola, New York, United States, 11501
        • NYU Langone Hospital
      • New York, New York, United States, 10029
        • Mount Sinai Medical Center
      • New York, New York, United States, 10016
        • NYU Langone Hospital
    • North Carolina
      • Durham, North Carolina, United States, 27710
        • Duke University Medical Center
    • Ohio
      • Cleveland, Ohio, United States, 44106
        • Case Western Reserve University / University Hospitals Cleveland Medical Center
      • Columbus, Ohio, United States, 43210
        • James Cancer Hospital / Ohio State University
    • Pennsylvania
      • Pittsburgh, Pennsylvania, United States, 15213
        • University of Pittsburgh Medical Center (UPMC)/Hillman Cancer Center
    • South Carolina
      • Greenville, South Carolina, United States, 29605
        • Prisma Health
    • Tennessee
      • Nashville, Tennessee, United States, 37203
        • Tennessee Oncology-Nashville/Sarah Cannon Research Institute
    • Texas
      • Abilene, Texas, United States, 79606
        • Texas Oncology - West Texas
      • Dallas, Texas, United States, 75246
        • Texas Oncology, P.A. - Dallas
      • Houston, Texas, United States, 77030
        • MD Anderson Cancer Center / University of Texas
      • Waco, Texas, United States, 76712
        • Texas Oncology - Waco
    • Utah
      • Salt Lake City, Utah, United States, 84112
        • Huntsman Cancer Institute/University of Utah
    • Virginia
      • Fairfax, Virginia, United States, 22031
        • Virginia Cancer Specialists, PC
    • Washington
      • Seattle, Washington, United States, 98109
        • Seattle Cancer Care Alliance / University of Washington
      • Vancouver, Washington, United States, 98684
        • Northwest Cancer Specialists, P.C.
    • Wisconsin
      • Madison, Wisconsin, United States, 53792
        • Carbone Cancer Center / University of Wisconsin

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Confirmed objective response rate (cORR) per investigator assessment
Time Frame: 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
From start of treatment up to approximately 2 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Disease control rate (DCR) per investigator assessment
Time Frame: 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
From start of treatment up to approximately 2 years
Duration of response (DOR) per investigator assessment
Time Frame: 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.
From start of treatment up to approximately 2 years
Progression-free survival (PFS) per investigator assessment
Time Frame: 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.
From start of treatment up to approximately 2 years
Overall survival (OS)
Time Frame: From start of treatment up to approximately 4 years
OS is defined as the time from treatment initiation to death due to any cause.
From start of treatment up to approximately 4 years
Incidence of adverse events (AEs)
Time Frame: 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.
From start of treatment up to approximately 2 years
Incidence of laboratory abnormalities
Time Frame: From start of treatment up to approximately 2 years
To be summarized using descriptive statistics.
From start of treatment up to approximately 2 years
Incidence of dose alterations
Time Frame: From start of treatment up to approximately 2 years
From start of treatment up to approximately 2 years
Maximum concentration (Cmax)
Time Frame: Approximately 4 months, during first 6 cycles of treatment
To be summarized using descriptive statistics.
Approximately 4 months, during first 6 cycles of treatment
Trough concentration (Ctrough)
Time Frame: Approximately 4 months, during first 6 cycles of treatment
To be summarized using descriptive statistics.
Approximately 4 months, during first 6 cycles of treatment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Seagen Inc.

Investigators

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

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 11, 2021

Primary Completion (Actual)

November 1, 2023

Study Completion (Estimated)

May 31, 2025

Study Registration Dates

First Submitted

October 1, 2020

First Submitted That Met QC Criteria

October 1, 2020

First Posted (Actual)

October 8, 2020

Study Record Updates

Last Update Posted (Actual)

November 18, 2023

Last Update Submitted That Met QC Criteria

November 16, 2023

Last Verified

November 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • SGNTUC-019

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Urologic Neoplasms

Clinical Trials on tucatinib

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Norway

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe