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

Phase 2

Active, not recruiting

Conditions: Biliary Tract Neoplasms
Uterine Neoplasms
Urologic Neoplasms
Carcinoma, Non-Small-Cell Lung
HER2 Mutations Breast Neoplasms
Uterine Cervical Neoplasms

Interventions: Drug: tucatinib
Drug: trastuzumab
Drug: fulvestrant

Registration Number: NCT04579380

Lead Sponsor: Seagen, a wholly owned subsidiary of Pfizer

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.

Recruitment & Eligibility

Status: ACTIVE_NOT_RECRUITING

Sex: All

Target Recruitment: 217

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Tucatinib + Trastuzumab (+ Fulvestrant)	tucatinib	Tucatinib + trastuzumab (+ fulvestrant in hormone-receptor positive HER2-mutant breast cancer only)
Tucatinib + Trastuzumab (+ Fulvestrant)	trastuzumab	Tucatinib + trastuzumab (+ fulvestrant in hormone-receptor positive HER2-mutant breast cancer only)
Tucatinib + Trastuzumab (+ Fulvestrant)	fulvestrant	Tucatinib + trastuzumab (+ fulvestrant in hormone-receptor positive HER2-mutant breast cancer only)

Primary Outcome Measures

Name	Time	Method
Confirmed Objective Response Rate (cORR) as Assessed by Investigator	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)	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).

Secondary Outcome Measures

Name	Time	Method
Confirmed Disease Control Rate (DCR) as Assessed by Investigator	From the first dose study treatment until PD or death, whichever occurred first (approximately 52.7 months)	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.
Number of Participants With Treatment Emergent Adverse Events (TEAEs)	From first dose of the study treatment (Day 1) up to 30 days after the last dose of study treatment (approximately 52.7 months)	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.
Duration of Response (DOR) as Assessed by Investigator	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)	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.
Progression-Free Survival (PFS) as Assessed by Investigator	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)	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.
Overall Survival (OS)	From date of start of study treatment until date of death or censoring date (approximately 52.7 months)	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.
Number of Participants With Treatment Emergent Laboratory Test Abnormalities	From first dose of the study treatment (Day 1) up to 30 days after the last dose of study treatment (approximately 52.7 months)	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.
Number of Participants With Any Dose Modifications Due to AEs	From first dose of the study treatment (Day 1) up to the last dose of study treatment (approximately 52.7 months)	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.
Number of Participants With TEAEs of Special Interest	From first dose of the study treatment (Day 1) up to the last dose of study treatment (approximately 52.7 months)	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.
Maximum Concentration (Cmax) of Tucatinib	Cycle 3 Day 1: anytime within 1-4 hours post-dose
Trough Concentration (Ctrough) of Tucatinib	Cycle 3 Day 1: Predose

Trial Locations

Locations (66): HealthPartners Institute
🇺🇸
Saint Louis Park, Minnesota, United States
Texas Oncology, P.A. - Dallas
🇺🇸
Dallas, Texas, United States
Massachusetts General Hospital
🇺🇸
Boston, Massachusetts, United States
Duke University Medical Center
🇺🇸
Durham, North Carolina, United States
Case Western Reserve University / University Hospitals Cleveland Medical Center
🇺🇸
Cleveland, Ohio, United States
MD Anderson Cancer Center / University of Texas
🇺🇸
Houston, Texas, United States
Seattle Cancer Care Alliance / University of Washington
🇺🇸
Seattle, Washington, United States
Tennessee Oncology-Nashville/Sarah Cannon Research Institute
🇺🇸
Nashville, Tennessee, United States
IRCCS Istituto Romagnolo per lo Studio dei Tumori Dino Amadori- IRST S.r.l
🇮🇹
Meldola, Other, Italy
Istituto Europeo di Oncologia
🇮🇹
Milano, Other, Italy
Arizona Oncology Associates, PC - HAL
🇺🇸
Goodyear, Arizona, United States
Rocky Mountain Cancer Centers
🇺🇸
Boulder, Colorado, United States
Arizona Cancer Center / University of Arizona
🇺🇸
Tucson, Arizona, United States
Northwest Cancer Specialists, P.C.
🇺🇸
Vancouver, Washington, United States
Huntsman Cancer Institute/University of Utah
🇺🇸
Salt Lake City, Utah, United States
Charite Universitatsmedizin Berlin
🇩🇪
Berlin, Other, Germany
Virginia Cancer Specialists, PC
🇺🇸
Fairfax, Virginia, United States
Universitair Ziekenhuis Antwerpen
🇧🇪
Edegem, Other, Belgium
The Cancer Institute Hospital of JFCR
🇯🇵
Tokyo, Other, Japan
Seoul National University Boramae Medical Center
🇰🇷
Seoul, Other, Korea, Republic of
Hospital Universitario 12 de Octubre
🇪🇸
Madrid, Other, Spain
Hospital Clinico Universitario de Santiago de Compostela
🇪🇸
Santiago de Compostela, Other, Spain
Cliniques Universitaires Saint Luc
🇧🇪
Brussels, Other, Belgium
National Cancer Center Hospital
🇯🇵
Chuo-Ku, Other, Japan
AZ Sint-Maarten
🇧🇪
Mechelen, Other, Belgium
Seoul National University Bundang Hospital
🇰🇷
Seongnam-si, Other, Korea, Republic of
St. Marianna University School of Medicine
🇯🇵
Kawasaki-shi, Other, Japan
Fondazione IRCCS San Gerardo dei Tintori
🇮🇹
Monza, Other, Italy
Seoul National University Hospital
🇰🇷
Seoul, Other, Korea, Republic of
Samsung Medical Center
🇰🇷
Seoul, Other, Korea, Republic of
Hospital Universitario Vall d'Hebron
🇪🇸
Barcelona, Other, Spain
The Royal Marsden Hospital
🇬🇧
London, Other, United Kingdom
L'Institut Catala d'Oncologia
🇪🇸
L'Hospitalet de Llobregat, Other, Spain
Hospital Clinico Universitario de Valencia
🇪🇸
Valencia, Other, Spain
Sarah Cannon Research Institute UK
🇬🇧
London, Other, United Kingdom
The Royal Marsden Hospital (Surrey)
🇬🇧
Sutton, Other, United Kingdom
Severance Hospital, Yonsei University Health System
🇰🇷
Seoul, Other, Korea, Republic of
HonorHealth
🇺🇸
Phoenix, Arizona, United States
Nebraska Cancer Specialists
🇺🇸
Omaha, Nebraska, United States
H. Lee Moffitt Cancer Center and Research Institute
🇺🇸
Tampa, Florida, United States
Mayo Clinic Rochester
🇺🇸
Rochester, Minnesota, United States
Mayo Clinic Florida
🇺🇸
Jacksonville, Florida, United States
UC San Diego / Moores Cancer Center
🇺🇸
La Jolla, California, United States
Pacific Shores Medical Group
🇺🇸
Long Beach, California, United States
University Cancer & Blood Center, LLC
🇺🇸
Athens, Georgia, United States
Mount Sinai Medical Center
🇺🇸
New York, New York, United States
Washington University in St Louis
🇺🇸
Saint Louis, Missouri, United States
NYU Langone Hospital
🇺🇸
New York, New York, United States
James Cancer Hospital / Ohio State University
🇺🇸
Columbus, Ohio, United States
University of Pittsburgh Medical Center (UPMC)/Hillman Cancer Center
🇺🇸
Pittsburgh, Pennsylvania, United States
Prisma Health
🇺🇸
Greenville, South Carolina, United States
Texas Oncology - West Texas
🇺🇸
Abilene, Texas, United States
Texas Oncology - Waco
🇺🇸
Waco, Texas, United States
Regional Cancer Care Associates
🇺🇸
Manchester, Connecticut, United States
Lombardi Cancer Center / Georgetown University Medical Center
🇺🇸
Washington, District of Columbia, United States
Mayo Clinic Arizona
🇺🇸
Phoenix, Arizona, United States
Grand Hopital de Charleroi
🇧🇪
Charleroi, Other, Belgium
Academisch Ziekenhuis Groeninge
🇧🇪
Kortrijk, Other, Belgium
CHU de Liege
🇧🇪
Liege, Other, Belgium
National Cancer Center Hospital East
🇯🇵
Kashiwa-shi, Other, Japan
Aichi Cancer Center
🇯🇵
Nagoya-shi, Other, Japan
Kindai University Hospital
🇯🇵
Osakasayama, Other, Japan
Netherlands Cancer Institute
🇳🇱
Amsterdam, Other, Netherlands
Med Polonia Sp. z o. o.
🇵🇱
Poznan, Other, Poland
Carbone Cancer Center / University of Wisconsin
🇺🇸
Madison, Wisconsin, United States
Guy's Hospital
🇬🇧
London, United Kingdom