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

Carcinoma, Non-Small-Cell Lung Clinical Trial

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04579380
• Other study ID #: SGNTUC-019
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: January 11, 2021
• Est. completion date: May 31, 2025

Study information

• Verified date: November 2023
• Source: Seagen Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Active, not recruiting
• Enrollment: 217
• Est. completion date: May 31, 2025
• Est. primary completion date: November 1, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Biliary Tract Neoplasms
• Breast Neoplasms
• Carcinoma, Non-Small-Cell Lung
• Neoplasms
• Urologic Neoplasms
• Uterine Cervical Neoplasms
• Uterine Neoplasms

Intervention

Drug:
• tucatinib
300 mg orally twice daily
• 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
• 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.

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Seagen Inc.

Countries where clinical trial is conducted

United States,  Belgium,  Germany,  Italy,  Japan,  Korea, Republic of,  Netherlands,  Poland,  Spain,  United Kingdom, 

Outcome

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