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

NCT04579380Active, Not RecruitingPHASE2INTERVENTIONAL

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.

Key Facts

Lead Sponsor

Seagen, a wholly owned subsidiary of Pfizer

Enrollment

217

Start Date

2021-01-11

Completion Date

2023-11-01

Study Type

INTERVENTIONAL

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

Interventions

tucatinibtrastuzumabfulvestrant

Conditions

Uterine NeoplasmsUterine Cervical NeoplasmsBiliary Tract NeoplasmsUrologic NeoplasmsCarcinomaNon-Small-Cell LungHER2 Mutations Breast Neoplasms

Eligibility

Age Range

18 Years+

Sex

ALL

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.

Outcome Measures

Primary Outcomes

Confirmed Objective Response Rate (cORR) as Assessed by Investigator

Confirmed ORR was defined as the percentage of participants with best overall response of complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria version (v)1.1 as assessed by investigator and was considered as confirmed when subsequent response was at least 4 weeks after initial response. As per RECIST v1.1, CR: disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (\<)10 millimeter (mm). PR: at least a greater than or equal to (\>=)30 % decrease in the sum of diameters (SOD) of target lesions (longest for non-nodal target lesions and the short axes for nodal target lesions), taking as reference the baseline sum diameters. Disease progression (PD): at least \>=20% relative increase in SOD of target lesion taking as reference the smallest sum on study (including baseline sum if that is the smallest on study).

Time frame: 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

Confirmed Disease Control Rate (DCR) as Assessed by Investigator

DCR was defined as the percentage of participants with confirmed CR, PR, or stable disease (SD or non-CR/non-PD) according to RECIST v1.1 as assessed by investigator. As per RECIST v1.1, CR: disappearance of all target (T) lesions and non-target (NT) lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. PR: at least \>=30 % decrease in the SOD of target lesions (longest for non-nodal target lesions and the short axes for nodal target lesions), taking as reference the baseline sum diameters. PD: at least \>=20% relative increase in SOD of target lesions taking as reference the smallest sum on study (including baseline sum if that is the smallest on study). SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest SOD while on study and cannot have met criteria for PD previously.

Time frame: From the first dose study treatment until PD or death, whichever occurred first (approximately 52.7 months)

Duration of Response (DOR) as Assessed by Investigator

DOR: time from first documentation of confirmed CR/PR to first documentation of PD according to RECIST v1.1 or death from any cause, whichever occurred earlier. Per RECIST v1.1, CR: disappearance of all T/NT lesions(L). Any pathological lymph nodes (whether T/NT) must have reduction in short axis to \<10 mm. PR: at least \>=30 % decrease in SOD of TL, taking reference baseline sum diameters. PD: at least \>=20% relative increase in SOD of TL taking reference smallest sum on study. Participants who do not have PD \& were still on study at time of an analysis/ who have started new anticancer treatment/discontinue prior to documentation of PD were censored at date of last adequate response assessment documenting absence of PD. Participants who had PD/death occurred after two/more consecutive missing scheduled response assessments were censored at date of last adequate response assessment of CR, PR, SD,/non-CR/non-PD. Kaplan-Meier method was used for evaluation.

Time frame: 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)

Progression-Free Survival (PFS) as Assessed by Investigator

PFS was defined as time from the date of treatment initiation to date of PD as per RECIST v1.1 or death from any cause, whichever occurred first . As per RECIST v1.1, PD: least \>=20% relative increase in SOD of target lesions taking as reference the smallest sum on study (including baseline sum if that is smallest on study). Participants who do not have PD and were still on study at time of an analysis/ who have started new anticancer treatment/discontinue prior to documentation of PD were censored at date of last adequate response assessment documenting absence of PD. Participants who had PD or death occurred after two or more consecutive missing scheduled response assessments were censored at date of last adequate response assessment of CR, PR, SD,/non-CR/non-PD. Kaplan-Meier method was used for evaluation.

Time frame: 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)

Overall Survival (OS)

OS was defined as the time from treatment initiation to death due to any cause. For a participant who was not known to have died by the end of study follow-up, observation of OS was censored on the date the participant was last known to be alive (i.e., the date of last contact). Participants lacking data beyond the day of treatment initiation were censored on the date of treatment initiation (i.e., OS duration of 1 day). Kaplan-Meier method was used for evaluation.

Time frame: From date of start of study treatment until date of death or censoring date (approximately 52.7 months)

Number of Participants With Treatment Emergent Adverse Events (TEAEs)

An AE was any untoward medical occurrence in a participant or clinical investigational participant administered a medicinal product and which did not necessarily have a causal relationship with this treatment. A TEAE was defined as a newly occurring or worsening AE after the first dose of study treatment.

Time frame: From first dose of the study treatment (Day 1) up to 30 days after the last dose of study treatment (approximately 52.7 months)

Number of Participants With Treatment Emergent Laboratory Test Abnormalities

Treatment-emergent laboratory abnormalities were defined as abnormalities that are new or worsened on or after receiving the first dose of study treatment up to 30 days after the last dose of study treatment. The following laboratory abnormalities were assessed: A-) Hematology: hemoglobin decreased, leukocytes decreased, lymphocytes decreased and increased, neutrophils decreased and platelets decreased; B-) Chemistry: alanine aminotransferase increased, albumin decreased, alkaline phosphatase increased, aspartate aminotransferase increased, calcium corrected for albumin decreased and increased, creatinine increased, glomerular filtration rate estimated decreased, glucose decreased, lactate dehydrogenase increased, magnesium increased and decreased, potassium increased and decreased, sodium increased and decreased and total bilirubin increased.

Time frame: From first dose of the study treatment (Day 1) up to 30 days after the last dose of study treatment (approximately 52.7 months)

Number of Participants With Any Dose Modifications Due to AEs

Dose modification included dose hold, dose reduction, or discontinuation of drugs. Dose reductions or treatment interruption/discontinuation were made at the discretion of the investigator.

Time frame: From first dose of the study treatment (Day 1) up to the last dose of study treatment (approximately 52.7 months)

Number of Participants With TEAEs of Special Interest

An adverse event of special interest (AESI) were any serious or nonserious AE that were of scientific or medical concern as defined by the sponsor and specific to the program, for which ongoing monitoring and rapid communication to the sponsor were appropriate. A TEAE was defined as a newly occurring or worsening AE after the first dose of study treatment (tucatinib, trastuzumab or fulvestrant). AESIs for this study were related to hepatoxicity.

Time frame: From first dose of the study treatment (Day 1) up to the last dose of study treatment (approximately 52.7 months)

Maximum Concentration (Cmax) of Tucatinib

Time frame: Cycle 3 Day 1: anytime within 1-4 hours post-dose

Trough Concentration (Ctrough) of Tucatinib

Time frame: Cycle 3 Day 1: Predose

Locations

HonorHealth, Phoenix, United States

HonorHealth, Tempe, United States

The University of Arizona Cancer Center-North Campus, Tucson, United States

City of Hope at Huntington Beach, Huntington Beach, United States

City of Hope at Irvine Sand Canyon, Irvine, United States

Koman Family Outpatient Pavilion, La Jolla, United States

UC San Diego Medical Center - La Jolla (Jacobs Medical Center / Thornton Pavilion), La Jolla, United States

UC San Diego Moores Cancer Center- Investigational Drug Services, La Jolla, United States

UC San Diego Moores Cancer Center, La Jolla, United States

City of Hope at Long Beach Worsham, Long Beach, United States

City of Hope at Long Beach Elm, Long Beach, United States

City of Hope at Newport Beach Lido, Newport Beach, United States

City of Hope Torrance, Torrance, United States

Rocky Mountain Cancer Centers, Aurora, United States

Rocky Mountain Cancer Centers, Boulder, United States

Rocky Mountain Cancer Centers, Thornton, United States

Moffitt Cancer Center, Tampa, United States

Minnesota Oncology Hematology, PA, Coon Rapids, United States

Metro Minnesota Community Oncology Research Consortium (MMCORC), Saint Louis Park, United States

Washington University School of Medicine - Obstetrics & Gynecology [Academic Offices), St Louis, United States

Barnes-Jewish Hospital Investigational Drug Pharmacy (IDS), St Louis, United States

Washington University School of Medicine - Obstetrics & Gynecology, St Louis, United States

Washington University School of Medicine [Patient Clinics], St Louis, United States

Oncology Hematology West P.C. dba Nebraska Cancer Specialists, Omaha, United States

Oncology Hematology West P.C. dba Nebraska Cancer Specialists, Omaha, United States

NYU Langone Health - Long Island (Winthrop Hospital), Mineola, United States

Perlmutter Cancer Center at NYU Langone GYN Oncology Associates, Mineola, United States

Perlmutter Cancer Center at NYU Langone Hospital - Long Island, Mineola, United States

Laura and Isaac Perlmutter Cancer Center at NYU Langone, New York, United States

NYU Langone Medical Center, New York, United States

Icahn School of Medicine at Mount Sinai, New York, United States

Duke University Medical Center/Duke Cancer Center, Durham, United States

University Hospitals Cleveland Medical Center, Cleveland, United States

OSU Wexner Medical Center, CarePoint East, Columbus, United States

OSU Wexner Medical Center, Ohio State University Hospital East, Columbus, United States

OSU Wexner Medical Center, Arther G. James Cancer Hospital, and Solove Research Institute, Columbus, United States

OSU Wexner Medical Center, Investigational Drug Services(IP Ship to), Columbus, United States

Osu Wexner Medical Center, The Ohio State University Hospital, Columbus, United States

OSU Wexner Medical Center, Stephanie Spielman Comprehensive Breast Center, Columbus, United States

OSU Wexner Medical Center, Martha Morehouse Medical Plaza, Columbus, United States

OSU Wexner Medical Center, OutPatient Care Upper Arlington, Columbus, United States

OSU Wexner Medical Center, CarePoint Gahanna, Gahanna, United States

OSU Wexner Medical Center, Gynecologic Oncology at Mill Run, Hilliard, United States

OSU Wexner Medical Center, Outpatient Care Lewis Center, Lewis Center, United States

UH Minoff Health Center at Chagrin Highlands, Orange, United States

OSU Wexner Medical Center, Outpatient Care New Albany, Westerville, United States

Northwest Cancer Specialists, P.C., Portland, United States

Northwest Cancer Specialists, P.C., Portland, United States

Northwest Cancer Specialists, P.C., Tigard, United States

UPMC Hillman Cancer Center - Washington, Washington, United States

Prisma Health Cancer Institute, Boiling Springs, United States

Prisma Health Cancer Institute, Easley, United States

Prisma Health Cancer Institute, Greenville, United States

Prisma Health Cancer Institute, Greenville, United States

Prisma Health Cancer Institute, Greer, United States

Prisma Health Cancer Institute, Seneca, United States

Tennessee Oncology, PLLC, Gallatin, United States

Tennessee Oncology, PLLC, Hendersonville, United States

Tennessee Oncology, PLLC, Nashville, United States

Tennessee Oncology, PLLC, Shelbyville, United States

Texas oncology-West Texas, Abilene, United States

US Oncology Investigational Product Center (IPC), Irving, United States

US Oncology Investigational Products Center (IPC), Irving, United States

US Oncology lnvestigational Products Center (IPC), Irving, United States

Texas Oncology - Central South, Waco, United States

Huntsman Cancer Institute, University of Utah, Salt Lake City, United States

Virginia Cancer Specialists, PC, Alexandria, United States

Virginia Cancer Specialists, PC, Arlington, United States

Virginia Cancer Specialists, PC, Fairfax, United States

Virginia Cancer Specialists, PC, Gainesville, United States

Fred Hutchinson Cancer Center, Seattle, United States

University of Washington Medical Center, Seattle, United States

Northwest Cancer Specialists, P.C., Vancouver, United States

1 S Park St Medical Center, Madison, United States

University of Wisconsin Clinical Science Center, Madison, United States

Grand Hopital de Charleroi, Charleroi, Belgium

Cliniques Universitaires Saint-Luc, Brussels, Belgium

Universitair Ziekenhuis Antwerpen, Edegem, Belgium

AZ Groeninge, Kortrijk, Belgium

CHU de Liege, Liège, Belgium

AZ Sint-Maarten, Mechelen, Belgium

Charite Universitatsmedizin Berlin, Berlin, Germany

Divisione di Sviluppo di Nuovi Farmaci per Terapie Innovative lstituto Europeo di Oncologia, Milan, Italy

Aichi Cancer Center Hospital, Nagoya, Japan

National Cancer Center Hospital East, Kashiwa-shi, Japan

St. Marianna University School of Medicine Hospital, Kawasaki, Japan

Kindai University Hospital, Osakasayama-shi, Japan

National Cancer Center Hospital, Cho-ku, Japan

The Cancer Institute Hospital of JFCR, Tokyo, Japan

Seoul National University Bundang Hospital, Seongnam-si, South Korea

Severance Hospital Yonsei University Health System, Seoul, South Korea

Seoul National University Hospital, Seoul, South Korea

Samsung Medical Center, Seoul, South Korea

Institut Catala d'Oncologia Hospitalet, L'Hospitalet de Llobregat, Spain

Cetir Centre Medic, Barcelona, Spain

Hospital Clínico Universitario de Valencia. Fundación Investigación Clínico de Valencia., Valencia, Spain

Ascires Eresa Campanar, Valencia, Spain

Hospital Vithas Valencia 9 de Octubre, Valencia, Spain

Sarah Cannon Research Institute UK, London, United Kingdom

Diagnostic Centre, London, United Kingdom

The Royal Marsden NHS Foundation Trust, Sutton, United Kingdom

Guy's Hospital, London, United Kingdom

Jonathan Poon, London, United Kingdom

The Royal Marsden NHS Foundation Trust, London, United Kingdom

The Harley Street Clinic, London, United Kingdom

Radiology, London, United Kingdom

Linked Diseases

Uterine Neoplasms

Uterine Neoplasms — a type of gynecological cancer.

Uterine Cervical Neoplasms

Uterine Cervical Neoplasms — a type of gynecological cancer.