Clinical trial NCT04579380: 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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Uterine Neoplasms
Uterine Cervical Neoplasms
Biliary Tract Neoplasms
Urologic Neoplasms
Carcinoma, Non-Small-Cell Lung
HER2 Mutations Breast Neoplasms
Keywords: 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
Lead sponsor: Seagen Inc.
Sponsor class: INDUSTRY
First posted: 2020-10-08
Enrollment: 217
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Confirmed Objective Response Rate (cORR) as Assessed by Investigator
timeFrame: 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:
measure: Confirmed Disease Control Rate (DCR) as Assessed by Investigator
timeFrame: From the first dose study treatment until PD or death, whichever occurred first (approximately 52.7 months)
measure: Duration of Response (DOR) as Assessed by Investigator
timeFrame: 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)
measure: Progression-Free Survival (PFS) as Assessed by Investigator
timeFrame: 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)
measure: Overall Survival (OS)
timeFrame: From date of start of study treatment until date of death or censoring date (approximately 52.7 months)
measure: Number of Participants With Treatment Emergent Adverse Events (TEAEs)
timeFrame: From first dose of the study treatment (Day 1) up to 30 days after the last dose of study treatment (approximately 52.7 months)
measure: Number of Participants With Treatment Emergent Laboratory Test Abnormalities
timeFrame: From first dose of the study treatment (Day 1) up to 30 days after the last dose of study treatment (approximately 52.7 months)
measure: Number of Participants With Any Dose Modifications Due to AEs
timeFrame: From first dose of the study treatment (Day 1) up to the last dose of study treatment (approximately 52.7 months)
measure: Number of Participants With TEAEs of Special Interest
timeFrame: From first dose of the study treatment (Day 1) up to the last dose of study treatment (approximately 52.7 months)
measure: Maximum Concentration (Cmax) of Tucatinib
timeFrame: Cycle 3 Day 1: anytime within 1-4 hours post-dose
measure: Trough Concentration (Ctrough) of Tucatinib
timeFrame: Cycle 3 Day 1: Predose
Other outcomes:
Locations:
city: Goodyear
country: United States
facility: Arizona Oncology Associates, PC - HAL
state: Arizona
city: Phoenix
country: United States
facility: HonorHealth
state: Arizona
city: Phoenix
country: United States
facility: Mayo Clinic Arizona
state: Arizona
city: Tucson
country: United States
facility: Arizona Cancer Center / University of Arizona
state: Arizona
city: La Jolla
country: United States
facility: UC San Diego / Moores Cancer Center
state: California
city: Long Beach
country: United States
facility: Pacific Shores Medical Group
state: California
city: Boulder
country: United States
facility: Rocky Mountain Cancer Centers
state: Colorado
city: Manchester
country: United States
facility: Regional Cancer Care Associates
state: Connecticut
city: Washington
country: United States
facility: Lombardi Cancer Center / Georgetown University Medical Center
state: District of Columbia
city: Jacksonville
country: United States
facility: Mayo Clinic Florida
state: Florida
city: Tampa
country: United States
facility: H. Lee Moffitt Cancer Center and Research Institute
state: Florida
city: Athens
country: United States
facility: University Cancer & Blood Center, LLC
state: Georgia
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Rochester
country: United States
facility: Mayo Clinic Rochester
state: Minnesota
city: Saint Louis Park
country: United States
facility: HealthPartners Institute
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University in St Louis
state: Missouri
city: Omaha
country: United States
facility: Nebraska Cancer Specialists
state: Nebraska
city: Mineola
country: United States
facility: NYU Langone Hospital
state: New York
city: New York
country: United States
facility: NYU Langone Hospital
state: New York
city: New York
country: United States
facility: Mount Sinai Medical Center
state: New York
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Cleveland
country: United States
facility: Case Western Reserve University / University Hospitals Cleveland Medical Center
state: Ohio
city: Columbus
country: United States
facility: James Cancer Hospital / Ohio State University
state: Ohio
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center (UPMC)/Hillman Cancer Center
state: Pennsylvania
city: Greenville
country: United States
facility: Prisma Health
state: South Carolina
city: Nashville
country: United States
facility: Tennessee Oncology-Nashville/Sarah Cannon Research Institute
state: Tennessee
city: Abilene
country: United States
facility: Texas Oncology - West Texas
state: Texas
city: Dallas
country: United States
facility: Texas Oncology, P.A. - Dallas
state: Texas
city: Houston
country: United States
facility: MD Anderson Cancer Center / University of Texas
state: Texas
city: Waco
country: United States
facility: Texas Oncology - Waco
state: Texas
city: Salt Lake City
country: United States
facility: Huntsman Cancer Institute/University of Utah
state: Utah
city: Fairfax
country: United States
facility: Virginia Cancer Specialists, PC
state: Virginia
city: Seattle
country: United States
facility: Seattle Cancer Care Alliance / University of Washington
state: Washington
city: Vancouver
country: United States
facility: Northwest Cancer Specialists, P.C.
state: Washington
city: Madison
country: United States
facility: Carbone Cancer Center / University of Wisconsin
state: Wisconsin
city: Brussels
country: Belgium
facility: Cliniques Universitaires Saint Luc
state: Other
city: Charleroi
country: Belgium
facility: Grand Hopital de Charleroi
state: Other
city: Edegem
country: Belgium
facility: Universitair Ziekenhuis Antwerpen
state: Other
city: Kortrijk
country: Belgium
facility: Academisch Ziekenhuis Groeninge
state: Other
city: Liege
country: Belgium
facility: CHU de Liege
state: Other
city: Mechelen
country: Belgium
facility: AZ Sint-Maarten
state: Other
city: Berlin
country: Germany
facility: Charite Universitatsmedizin Berlin
state: Other
city: Meldola
country: Italy
facility: IRCCS Istituto Romagnolo per lo Studio dei Tumori Dino Amadori- IRST S.r.l
state: Other
city: Milano
country: Italy
facility: Istituto Europeo di Oncologia
state: Other
city: Monza
country: Italy
facility: Fondazione IRCCS San Gerardo dei Tintori
state: Other
city: Chuo-Ku
country: Japan
facility: National Cancer Center Hospital
state: Other
city: Kashiwa-shi
country: Japan
facility: National Cancer Center Hospital East
state: Other
city: Kawasaki-shi
country: Japan
facility: St. Marianna University School of Medicine
state: Other
city: Nagoya-shi
country: Japan
facility: Aichi Cancer Center
state: Other
city: Osakasayama
country: Japan
facility: Kindai University Hospital
state: Other
city: Tokyo
country: Japan
facility: The Cancer Institute Hospital of JFCR
state: Other
city: Seongnam-si
country: Korea, Republic of
facility: Seoul National University Bundang Hospital
state: Other
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
state: Other
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
state: Other
city: Seoul
country: Korea, Republic of
facility: Seoul National University Boramae Medical Center
state: Other
city: Seoul
country: Korea, Republic of
facility: Severance Hospital, Yonsei University Health System
state: Other
city: Amsterdam
country: Netherlands
facility: Netherlands Cancer Institute
state: Other
city: Poznan
country: Poland
facility: Med Polonia Sp. z o. o.
state: Other
city: Barcelona
country: Spain
facility: Hospital Universitario Vall d'Hebron
state: Other
city: L'Hospitalet de Llobregat
country: Spain
facility: L'Institut Catala d'Oncologia
state: Other
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
state: Other
city: Santiago de Compostela
country: Spain
facility: Hospital Clinico Universitario de Santiago de Compostela
state: Other
city: Valencia
country: Spain
facility: Hospital Clinico Universitario de Valencia
state: Other
city: London
country: United Kingdom
facility: The Royal Marsden Hospital
state: Other
city: London
country: United Kingdom
facility: Sarah Cannon Research Institute UK
state: Other
city: Sutton
country: United Kingdom
facility: The Royal Marsden Hospital (Surrey)
state: Other
city: London
country: United Kingdom
facility: Guy's Hospital
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: