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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04579380
Recruitment Status : Recruiting
First Posted : October 8, 2020
Last Update Posted : June 28, 2022
Sponsor:
Information provided by (Responsible Party):
Seagen Inc.

Study Description
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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.


Condition or disease Intervention/treatment Phase
Uterine Neoplasms Uterine Cervical Neoplasms Biliary Tract Neoplasms Urologic Neoplasms Carcinoma, Non-Small-Cell Lung HER2 Mutations Breast Neoplasms Drug: tucatinib Drug: trastuzumab Drug: fulvestrant Phase 2

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
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Study Type : Interventional  (Clinical Trial)
Estimated 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 : January 11, 2021
Estimated Primary Completion Date : January 31, 2023
Estimated Study Completion Date : May 31, 2025

Resource links provided by the National Library of Medicine


Arms and Interventions
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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 Name: 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 Name: 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 Name: Faslodex


Outcome Measures
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Primary Outcome Measures :
  1. 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


Secondary Outcome Measures :
  1. 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

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. Incidence of laboratory abnormalities [ Time Frame: From start of treatment up to approximately 2 years ]
    To be summarized using descriptive statistics.

  7. Incidence of dose alterations [ Time Frame: From start of treatment up to approximately 2 years ]
  8. Maximum concentration (Cmax) [ Time Frame: Approximately 4 months, during first 6 cycles of treatment ]
    To be summarized using descriptive statistics.

  9. Trough concentration (Ctrough) [ Time Frame: Approximately 4 months, during first 6 cycles of treatment ]
    To be summarized using descriptive statistics.


Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04579380


Contacts
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Contact: Seagen Trial Information Support 8663337436 clinicaltrials@seagen.com

Locations
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Sponsors and Collaborators
Seagen Inc.
Investigators
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Study Director: Jorge Ramos, DO Seagen Inc.
More Information
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Responsible Party: Seagen Inc.
ClinicalTrials.gov Identifier: NCT04579380    
Other Study ID Numbers: SGNTUC-019
First Posted: October 8, 2020    Key Record Dates
Last Update Posted: June 28, 2022
Last Verified: June 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Seagen Inc.:
Cervical cancer
Uterine cancer
Biliary tract cancer
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
Additional relevant MeSH terms:
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Neoplasms
Breast Neoplasms
Carcinoma, Non-Small-Cell Lung
Uterine Cervical Neoplasms
Uterine Neoplasms
Biliary Tract Neoplasms
Urologic Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Lung Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
 Lung Diseases
Respiratory Tract Diseases
Genital Neoplasms, Female
Urogenital Neoplasms
Uterine Cervical Diseases
Uterine Diseases
Digestive System Neoplasms
Biliary Tract Diseases
Digestive System Diseases
Trastuzumab
Fulvestrant
Tucatinib
Antineoplastic Agents, Immunological
Antineoplastic Agents
Antineoplastic Agents, Hormonal