A Study of Tucatinib vs. Placebo in Combination With Ado-trastuzumab Emtansine (T-DM1) for Patients With Advanced or Metastatic HER2+ Breast Cancer

HER2-positive Breast Cancer Clinical Trial

Official title:

Randomized, Double-blind, Phase 3 Study of Tucatinib or Placebo in Combination With Ado-trastuzumab Emtansine (T-DM1) for Subjects With Unresectable Locally-advanced or Metastatic HER2+ Breast Cancer (HER2CLIMB-02)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03975647
• Other study ID #: SGNTUC-016
• Status: Recruiting
• Phase: Phase 3
• Start date: October 2, 2019
• Est. completion date: October 31, 2027

Study information

• Verified date: June 2024
• Source: Seagen Inc.
• Contact: Seagen Trial Information Support
• Phone: 866-333-7436
• Email: clinicaltrials[@]seagen.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study is being done to see if tucatinib with ado-trastuzumab emtansine (T-DM1) works better than T-DM1 alone to help patients who have a specific type of breast cancer called HER2 positive breast carcinoma. The breast cancer in this study is either metastatic (spread into other parts of the body) or cannot be removed completely with surgery.

Patients in this study will be randomly assigned to get either tucatinib or placebo (a pill with no medicine). This is a blinded study, so neither patients nor their doctors will know whether a patient gets tucatinib or placebo. All patients in the study will get T-DM1, a drug that is often used to treat this cancer.

Each treatment cycle lasts 21 days. Patients will swallow tucatinib pills or placebo pills two times every day. Patients will get T-DM1 injections from the study site staff on the first day of every cycle.

Description:

This study is designed to evaluate the efficacy and safety of tucatinib in combination with T-DM1 in participants with unresectable locally-advanced or metastatic HER2+ breast cancer who have had prior treatment with a taxane and trastuzumab in any setting. Prior pertuzumab treatment is permitted, but not required. Participants will be randomized in a 1:1 manner to receive 21-day cycles of either tucatinib or placebo in combination with T-DM1.

While on study treatment, participants will be assessed for progression every 6 weeks for the first 24 weeks, and every 9 weeks thereafter, irrespective of dose holds or interruptions. Study treatment will continue until unacceptable toxicity, disease progression, withdrawal of consent, or study closure. After completion of study treatment and after occurrence of disease progression, participants in both arms of the study will continue to be followed for survival until study closure or withdrawal of consent.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 565
• Est. completion date: October 31, 2027
• Est. primary completion date: June 29, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

• Inclusion Criteria:

• Histologically confirmed HER2+ breast carcinoma as determined by a sponsor-designated central laboratory

• History of prior treatment with a taxane and trastuzumab in any setting, separately or in combination

• Have progression of unresectable locally advanced/metastatic breast cancer after last systemic therapy, or be intolerant of last systemic therapy

• Measurable or non-measurable disease assessable by RECIST v1.1

• ECOG performance status score of 0 or 1

• CNS Inclusion - Based on screening contrast brain magnetic resonance imaging (MRI), participants must have at least one of the following:

(a) No evidence of brain metastases

(b) Untreated brain metastases not needing immediate local therapy

(c) Previously treated brain metastases

1. Brain metastases previously treated with local therapy may either be stable since treatment or may have progressed since prior local CNS therapy, provided that there is no clinical indication for immediate re-treatment with local therapy

2. Participants treated with CNS local therapy for newly identified lesions or previously treated and progressing lesions may be eligible to enroll if all of the following criteria are met:

(i) Time since SRS is at least 7 days prior to first dose of study treatment, time since WBRT is at least 14 days prior to first dose, or time since surgical resection is at least 28 days.

(ii) Other sites of evaluable disease are present

3. Relevant records of any CNS treatment must be available to allow for classification of target and non-target lesions

• Exclusion Criteria:

• Prior treatment with tucatinib, afatinib, trastuzumab deruxtecan (DS-8201a), or any other investigational anti-HER2, anti-EGFR, or HER2 TKI agent. Prior treatment with lapatinib or neratinib within 12 months of starting study treatment (except in cases where they were given for =21 days and was discontinued for reasons other than disease progression or severe toxicity). Prior treatment with pyrotinib for recurrent of mBC (except in cases where pyrotinib was given for =21 days and was discontinued for reasons other than disease progression or severe toxicity).

• CNS Exclusion - Based on screening contrast brain magnetic resonance imaging (MRI), participants must not have any of the following:

1. Any untreated brain lesions >2 cm in size

2. Ongoing use of corticosteroids for control of symptoms of brain metastases at a total daily dose of >2 mg of dexamethasone (or equivalent).

3. Any brain lesion thought to require immediate local therapy

4. Known or concurrent leptomeningeal disease as documented by the investigator

5. Poorly controlled generalized or complex partial seizures

Related Conditions & MeSH terms

• Breast Neoplasms
• HER2-positive Breast Cancer

Intervention

Drug:
• tucatinib
300mg given twice per day by mouth (orally)
• placebo
Given twice per day orally
• T-DM1
3.6 mg/kg given into the vein (IV; intravenously) every 21 days

Locations

Country	Name	City	State
Australia	Austin Health	Melbourne	Other
Australia	Peter MacCallum Cancer Centre	Melbourne	Other
Australia	Breast Cancer Research Centre	Nedlands	Other
Australia	Mater Hospital	Sydney	Other
Australia	Westmead Hospital	Westmead	Other
Austria	LKH- Universitat Klinikum Graz	Graz	Other
Austria	Medizinische Universitat Innsbruck	Innsbruck	Other
Austria	LKH Salzburg, Universitatsklinikum der PMU	Salzburg	Other
Austria	Klinik Ottakring	Vienna	Other
Austria	Medizinische Universitat Wien	Vienna	Other
Belgium	Institut Jules Bordet	Anderlecht	Other
Belgium	Cliniques Universitaires Saint Luc	Brussels	Other
Belgium	Grand Hôpital de Charleroi - Saint-Joseph	Charleroi	Other
Belgium	Universitair Ziekenhuis Antwerpen	Edegem	Other
Belgium	Academisch Ziekenhuis Groeninge	Kortrijk	Other
Belgium	CHU de Liege	Liege	Other
Belgium	Universitair Ziekenhuis Leuven	Lueven	Other
Belgium	CHU UCL Namur-Site de Saint Elisabeth	Namur	Other
Canada	University of Alberta / Cross Cancer Institute	Edmonton	Alberta
Canada	Queen Elizabeth II Health Sciences Centre	Halifax	Nova Scotia
Canada	Cancer Centre of Southeastern Ontario At Kingston General Hospital	Kingston	Ontario
Canada	London Health Sciences Centre - Victoria Hospital	London	Ontario
Canada	Centre Hospitalier de l'Universite de Montreal	Montreal	Quebec
Canada	Jewish General Hospital	Montreal	Quebec
Canada	University of Ottawa / Ottawa General Hospital	Ottawa	Ontario
Canada	Hopital du Saint-Sacrement, CHU de Quebec-Universite Laval	Quebec
Canada	Saskatoon Cancer Centre	Saskatoon	Saskatchewan
Canada	University Health Network, Princess Margaret Hospital	Toronto	Ontario
China	Peking University People's Hospital	Beijing	Other
China	Cancer Hospital Chinese Academy of Medical Sciences	Beijing City	Other
China	Bejing Hospital	Bejing
China	Jilin Province Cancer Hospital	Changghun	Other
China	Hunan Cancer Hospital	Changsha	Other
China	Center of Women and Children Hospital of Guangdong Province	Guangzhou
China	Guangdong Provincial People's Hospital	Guangzhou	Other
China	Sun Yat-sen University Cancer Center	Guangzhou City	Other
China	The Second Affiliated Hospital of Zhejiang University School of Medicine	Hangzhou	Other
China	First Affiliated Hospital of Zhejiang University	Hangzhou City	Other
China	Zhejiang Cancer Hospital	Hangzhou City	Other
China	Shandong Cancer Hospital	Jinan	Other
China	Nanchang Third Hospital	Nanchang City
China	Gulou Hospital Affiliated to Nanjing University Medical College	Nanjing	Other
China	Guangxi Medical University Affiliated Tumor Hospital	Nanning
China	Shengjing Hospital of China Medical University	Shenyang City	Other
China	Tianjin Medical University - Cancer Institute & Hospital	Tianjin	Other
China	Hubei Cancer Hospital	Wuhan	Other
China	Wuhan University	Wuhan	Other
China	The First Affiliated Hospital of Xi'an Jiaotong University	Xi'an	Other
China	Xi'An International Medical Center Hospital	Xi'An	Other
China	The Affiliated Hospital of Xuzhou Medical College	Xuzhou	Other
China	Xuzhou Central Hospital	Xuzhou	Other
China	The Affiliated Hospital of Guangdong Medical University	Zhan Jiang City	Other
China	Henan Cancer Hospital	Zhengzhou	Other
China	Zigong First People's Hospital	Zigong City	Other
Denmark	Aalborg Universitetshospital	Aalborg	Other
Denmark	Aarhus University Hospital	Aarhus N	Other
Denmark	Rigs Hospiltalet	Copenhagen	Other
Denmark	Herlev Hospital	Herlev	Other
Denmark	Odense University Hospital	Odense C	Other
Denmark	Sygehus Lillebaelt - Vejle Sygehus	Vejle	Other
France	University Hospital of Besancon	Besancon cedex	Other
France	Hospital Center Regional University Morvan De Brest	Brest	Other
France	Centre de Lutte contre le Cancer - Francois Baclesse	Caen Cedex 5	Other
France	Hopital Europeen Georges Pompidou	Cedex 15	Other
France	Center Georges Francois Leclerc	Dijon	Other
France	Clinique Victor Hugo Le Mans	Le Mans	Other
France	Centre Leon Berard - Centre regional de lutte contre le cancer Rhone-Alpes	Lyon cedex 08	Other
France	Institut Paoli Calmettes	Marseille	Other
France	Institute Curie - Centre de Lutte Contre Le Cancer CLCC de Paris	Paris	Other
France	Hopital Saint-Louis / Service d'Hematologie	Paris Cedex 10	Other
France	Centre Henri Becquerel / Centre Regional de Lutte Contre le Cancer	Rouen	Other
France	Hopitaux Universitaires de Strasbourg	Strasbourg	Other
France	Institut Claudius Regaud IUCT-O	Toulouse Cedex 9	Other
France	CHU Tours - Hopital Bretonneau	TOURS Cedex 09	Other
Germany	Helios Klinikum Berlin-Buch	Berlin	Other
Germany	Stadtisches Klinikum Dessau	Dessau-Rosslau	Other
Germany	Kliniken Essen-Mitte - Evang. Huyssens-Stiftung	Essen	Other
Germany	CHOP GmbH	Frankfurt	Other
Germany	Universitaetsklinikum Hamburg-Eppendorf (UKE)	Hamburg	Other
Germany	Universitatsklinikum Heidelberg	Heidelberg	Other
Germany	Universitatsklinikum Schleswig-Holstein	Kiel	Other
Germany	InVO- Institut fUr Versorgungsforschung in der onkologie GbR	Koblenz	Other
Germany	Universitaetsmedizin der Johannes Gutenberg-Universitaet Mainz	Mainz	Other
Germany	Klinikum Rechts der Isar der Technischen Universitaet Muenchen	Muenchen	Other
Germany	Klinikum der Universitat Munchen	Munchen	Other
Germany	Sana Klinikum Offenbach GmbH	Offenbach am Main	Other
Germany	University of Rostock	Rostock	Other
Israel	Shaare Zedek Medical Center	Jerusalem	Other
Israel	Meir Medical Center	Kfar Saba	Other
Israel	Rabin Medical Center	Petach Tikva	Other
Israel	Kaplan Medical Center	Rehovot	Other
Italy	Azienda Ospedaliero-Universitaria di Bologna Policlinico S. Orsola-Malpighi	Bologna	Other
Italy	Fondazione del Piemonte per l'Oncologia - Istituto di Candiolo FPO - IRCCS	Candiolo	Other
Italy	Irccs Irst	Meldola	Other
Italy	Istituto Europeo di Oncologia	Milano	Other
Italy	Seconda Università degli Studi di Napoli, AOU	Napoli	Other
Italy	Nuovo Ospedale di Prato - Santo Stefano	Prato	Other
Italy	Ospedale degli Infermi	Rimini	Other
Italy	Policlinico Universitario Agostino Gemelli	Roma	Other
Italy	Azienda Ospedaliera S. Maria di Terni	Terni	Other
Italy	A.O.U. - Ospedali Riuniti di Ancona	Torrette	Other
Japan	Chiba Cancer Center	Chiba	Other
Japan	National Cancer Center Hospital	Chuo-ku	Other
Japan	National Hospital Organization Kyushu Cancer Center	Fukuoka-shi	Other
Japan	Hiroshima City Hiroshima Citizens Hospital	Hiroshima	Other
Japan	University of Tsukuba Hospital	Ibaraki	Other
Japan	Hakuaikai Sagara Hospital/Breast Surgery	Kagosima	Other
Japan	Kameda General Hospital	Kamogawa	Other
Japan	National Cancer Center Hospital East	Kashiwa-shi	Other
Japan	Saitama Cancer Center	Kitaadachi-gun	Other
Japan	Kumamoto Shinto General Hospital	Kumamoto	Other
Japan	NHO Shikoku Cancer Center	Matsuyama	Other
Japan	Aichi Cancer Center	Nagoya-shi	Other
Japan	Hyogo College of Medicine Hospital	Nishinomiya	Other
Japan	National Hospital Organization Osaka	Osaka	Other
Japan	Osaka International Cancer Institute	Osaka	Other
Japan	National Hospital Organization Hokkaido Cancer Center	Sapporo	Other
Japan	Shizuoka Cancer Center	Sunto-Gun	Other
Japan	The Cancer Institute Hospital of JFCR	Tokyo	Other
Japan	Kanagawa Cancer Center	Yokohama	Other
Korea, Republic of	National Cancer Center	Goyang-si	Other
Korea, Republic of	Seoul National University Bundang Hospital	Seongnam-si	Other
Korea, Republic of	Asan Medical Center - Oncology	Seoul	Other
Korea, Republic of	Korea University Anam Hospital	Seoul	Other
Korea, Republic of	Samsung 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	Isala Ziekenhuis Zwolle	AB Zwolle	Other
Netherlands	Netherlands Cancer Institute	Amsterdam	Other
Netherlands	Amphia Ziekenhuis	Breda	Other
Netherlands	Reinier de Graaf Hospital	Delft	Other
Netherlands	Martini Ziekenhuis	Groningen	Other
Netherlands	University Medical Center Groningen	Groningen	Other
Netherlands	Maastricht University Medical Center	Maastricht	Other
Netherlands	Erasmus Medisch Centrum Daniel Den Hoed	Rotterdam	Other
Singapore	National Cancer Centre Singapore	Singapore	Other
Singapore	National University Cancer Institute, Singapore	Singapore	Other
Spain	Hospital del Mar	Barcelona	Other
Spain	Hospital Universitari Vall d'Hebron	Barcelona	Other
Spain	Hospital Universitario Reina Sofia	Cordoba	Other
Spain	Hospital Clinico San Carlos	Madrid	Other
Spain	Hospital General Universitario Gregorio Marañon	Madrid	Other
Spain	Hospital Ruber Internacional	Madrid	Other
Spain	Hospital Universitario HM Sanchinarro	Madrid	Other
Spain	Hospital Universitario Virgen de la Victoria	Malaga	Other
Spain	Hospital Universitario Son Espases	Palma de Mallorca	Other
Spain	L'Institut Catala d'Oncologia	Saint Joan Despi	Other
Spain	Hospital Universitario de Canarias	San Cristóbal de la Laguna	Other
Spain	Hospital Universitario Virgen del Rocio	Sevilla	Other
Spain	Hospital Clinico Universitario de Valencia	Valencia	Other
Spain	Hospital Universitario Miguel Servet	Zaragoza	Other
Sweden	Goteborgs Universitet - Sahlgrenska Akademin - Institutionen For Kliniska Vetenskaper (Institute Of Clinical Sciences)	Gothenburg	Other
Sweden	Ryhov Hospital	Jonkoping	Other
Sweden	Skanes University Hospital - Universitetssjukhus	Lund	Other
Sweden	Orebro University Hospital	Orebro	Other
Sweden	Onkologklinike Sodersjukhuset	Stockholm	Other
Switzerland	University Hospital Basel - Brustzentrum	Basel	Other
Switzerland	Institute of Oncology of Southern Switzerland	Bellinzona	Other
Switzerland	University Hospital Lausanne CHUV	Lausanne	Other
Switzerland	Kantonsspital Winterthur (KSW)	Winterthur	Other
Taiwan	National Cheng-Kung University Hospital	Tainan	Other
Taiwan	National Taiwan University Hospital	Tainan	Other
United Kingdom	University Hospitals Birmingham NHS Foundation Trust	Birmingham	Other
United Kingdom	Addenbrooke's Hospital	Cambridge	Other
United Kingdom	The University of Edinburgh	Edinburgh	Other
United Kingdom	Oxford University Hospitals	Headington	Other
United Kingdom	Sarah Cannon Research Institute UK	London	Other
United Kingdom	The Royal Marsden NHS Foundation Trust (RM)	London	Other
United Kingdom	Maidstone and Tunbridge Wells NHS Trust	Maidstone	Other
United Kingdom	The Christie NHS Foundation Trust	Manchester	Other
United Kingdom	The Newcastle upon Tyne Hospitals NHS Foundation Trust	Newcastle Upon Tyne	Other
United Kingdom	Mount Vernon Hospital, UK	Northwood	Other
United Kingdom	The Royal Marsden Hospital (Surrey)	Sutton	Other
United Kingdom	Royal Cornwall Hospitals NHS Trust	Truro	Other
United States	New York Oncology Hematology, P.C.	Albany	New York
United States	Texas Oncology - Amarillo	Amarillo	Texas
United States	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan
United States	Illinois Cancer Specialists - Arlington Heights	Arlington Heights	Illinois
United States	Winship Cancer Institute / Emory University School of Medicine	Atlanta	Georgia
United States	Augusta University	Augusta	Georgia
United States	Rocky Mountain Cancer Centers - Aurora	Aurora	Colorado
United States	University of Colorado Hospital / University of Colorado	Aurora	Colorado
United States	Texas Oncology - Austin Central	Austin	Texas
United States	Mercy Medical Center -Weinberg Center	Baltimore	Maryland
United States	University of Maryland	Baltimore	Maryland
United States	Texas Oncology - DFW	Bedford	Texas
United States	American Oncology Networks LLC	Bethesda	Maryland
United States	St. Vincent Frontier Cancer Center	Billings	Montana
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	Dana Farber Cancer Institute	Boston	Massachusetts
United States	SCL Health Good Samaritan Medical Center Cancer Centers of Colorado	Broomfield	Colorado
United States	Northside Hospital	Canton	Georgia
United States	Ironwood Cancer & Research Centers - Chandler	Chandler	Arizona
United States	UNC Lineberger Comprehensive Cancer Center / University of North Carolina	Chapel Hill	North Carolina
United States	Levine Cancer Institute	Charlotte	North Carolina
United States	Rush University Medical Center	Chicago	Illinois
United States	University of Chicago Medical Center	Chicago	Illinois
United States	University of Colorado Health Memorial Hospital	Colorado Springs	Colorado
United States	Texas Oncology - DFW	Dallas	Texas
United States	Texas Oncology - DFW	Dallas	Texas
United States	Texas Oncology - Medical City Dallas	Dallas	Texas
United States	University of Texas Southwestern Medical Center	Dallas	Texas
United States	Cancer Centers of Colorado - Denver	Denver	Colorado
United States	Henry Ford Health System	Detroit	Michigan
United States	City of Hope National Medical Center	Duarte	California
United States	Duke University Medical Center	Durham	North Carolina
United States	Swedish Cancer Institute - Edmonds	Edmonds	Washington
United States	California Cancer Associates for Research and Excellence Inc (cCARE)	Encinitas	California
United States	Virginia Cancer Specialists, PC	Fairfax	Virginia
United States	Summit Medical Group	Florham Park	New Jersey
United States	Poudre Valley Health System (PVHS)	Fort Collins	Colorado
United States	Florida Cancer Specialists - South Region	Fort Myers	Florida
United States	Ft Wayne Medical Oncology and Hematology, Inc TRIO	Fort Wayne	Indiana
United States	The Center for Cancer and Blood Disorders: Fortworth	Fort Worth	Texas
United States	St. Joseph Heritage Healthcare TRIO	Fullerton	California
United States	Banner MD Anderson Cancer Center	Gilbert	Arizona
United States	Cancer Treatment Centers of America / Western Regional Medical Center	Goodyear	Arizona
United States	Kaiser Permanente Moanalua Medical Center	Honolulu	Hawaii
United States	Kapi'olani Medical Center for Women and Children	Honolulu	Hawaii
United States	Baylor Clinic	Houston	Texas
United States	MD Anderson Cancer Center / University of Texas	Houston	Texas
United States	Oncology Consultants, PA	Houston	Texas
United States	Texas Oncology - Houston Memorial City	Houston	Texas
United States	Swedish Cancer Institute - Issaquah	Issaquah	Washington
United States	Baptist MD Anderson Cancer Center	Jacksonville	Florida
United States	St. Bernards Medical Center	Jonesboro	Arkansas
United States	HCA Midwest Health Kansas City	Kansas City	Missouri
United States	Saint Luke's Cancer Institute LLC	Kansas City	Missouri
United States	University of Kansas Medical Center	Kansas City	Kansas
United States	Brig Center for Cancer Care and Survivorship	Knoxville	Tennessee
United States	Comprehensive Cancer Centers of Nevada	Las Vegas	Nevada
United States	CHI Saint Joseph Medical Group Cancer Care Center	Lexington	Kentucky
United States	Saint Barnabas Medical Center Cancer Center	Livingston	New Jersey
United States	Miami Cancer Institute at Baptist Health, Inc.	Miami	Florida
United States	University of Miami	Miami	Florida
United States	Saint Francis Hospital / Bon Secours - Virginia	Midlothian	Virginia
United States	Minnesota Oncology Hematology P.A.	Minneapolis	Minnesota
United States	University of South Alabama - Mitchell Cancer Institute	Mobile	Alabama
United States	Tennessee Oncology-Nashville/Sarah Cannon Research Institute	Nashville	Tennessee
United States	Rutgers Cancer Institute of New Jersey	New Brunswick	New Jersey
United States	Ochsner Medical Center	New Orleans	Louisiana
United States	Helen F. Graham Cancer Center / Christiana Care Health Systems	Newark	Delaware
United States	Peninsula Cancer Institute	Newport News	Virginia
United States	Nebraska Cancer Specialists	Omaha	Nebraska
United States	Chao Family Comprehensive Cancer Center University of California Irvine	Orange	California
United States	University of California Irvine - Newport	Orange	California
United States	AdventHealth Cancer Institute	Orlando	Florida
United States	Orlando Health, Inc. TRIO	Orlando	Florida
United States	Illinois Cancer Care	Peoria	Illinois
United States	Cancer Treatment Centers of America / Eastern Regional Medical Center	Philadelphia	Pennsylvania
United States	University of Pennsylvania / Perelman Center for Advanced Medicine	Philadelphia	Pennsylvania
United States	Arizona Oncology Associates, PC - HAL	Phoenix	Arizona
United States	Oregon Health and Science University	Portland	Oregon
United States	Providence Portland Medical Center	Portland	Oregon
United States	Maryland Oncology Hematology, P.A.	Rockville	Maryland
United States	University of California Davis	Sacramento	California
United States	Washington University in St Louis	Saint Louis	Missouri
United States	Florida Cancer Specialists - North Region	Saint Petersburg	Florida
United States	Oncology and Hematology Assoc of SW VA DBA Blue Ridge Cancer Care	Salem	Virginia
United States	Huntsman Cancer Institute/University of Utah	Salt Lake City	Utah
United States	Texas Oncology - San Antonio Medical Center	San Antonio	Texas
United States	San Francisco General Hospital	San Francisco	California
United States	University of California, San Francisco | HDFCCC - Hematopoietic Malignancies	San Francisco	California
United States	UCLA Department of Medicine - Hematology & Oncology	Santa Monica	California
United States	Swedish Cancer Institute	Seattle	Washington
United States	Stony Brook University Cancer Center	Stony Brook	New York
United States	H. Lee Moffitt Cancer Center and Research Institute	Tampa	Florida
United States	Northwest Cancer Specialists, P.C.	Tigard	Oregon
United States	Torrance Memorial Physician Network - TRIO	Torrance	California
United States	Arizona Oncology Associates, PC - HOPE	Tucson	Arizona
United States	North Mississippi Medical Center Hematology Oncology - Tupelo	Tupelo	Mississippi
United States	Kaiser Permanente Medical Center Northern California	Vallejo	California
United States	Lombardi Cancer Center / Georgetown University Medical Center	Washington	District of Columbia
United States	Florida Cancer Specialists - East West Palm Beach, FL (SCRI)	West Palm Beach	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Seagen Inc.

Countries where clinical trial is conducted

United States,  Australia,  Austria,  Belgium,  Canada,  China,  Denmark,  France,  Germany,  Israel,  Italy,  Japan,  Korea, Republic of,  Netherlands,  Singapore,  Spain,  Sweden,  Switzerland,  Taiwan,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-free survival (PFS) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 by investigator assessment	PFS per investigator is defined as the time from the date of randomization to the investigator assessment of disease progression according to RECIST v1.1 or death from any cause, whichever occurs first.	Up to approximately 5 years
Secondary	Overall Survival	OS is defined as the time from randomization to death due to any cause.	Up to approximately 5 years
Secondary	PFS per RECIST v1.1 by blinded independent committee review (BICR)	PFS per BICR is defined as the time from the date of randomization to the centrally-reviewed documented disease progression according to RECIST v1.1 or death from any cause, whichever occurs first.	Up to approximately 5 years
Secondary	PFS per RECIST v1.1 by investigator assessment in participants with brain metastases at baseline (PFS.BM per investigator)	PFS.BM is defined as the time from the date of randomization in participants with brain metastases at baseline to the investigator assessment of disease progression according to RECIST v1.1 or death from any cause, whichever occurs first.	Up to approximately 5 years
Secondary	PFS.BM per RECIST v1.1 by BICR		Up to approximately 5 years
Secondary	Objective response rate (ORR) per RECIST v1.1 by investigator assessment	ORR is defined as the proportion of participants with complete response (CR) or partial response (PR) according to RECIST v1.1.	Up to approximately 3 years
Secondary	ORR per RECIST v1.1 by BICR		Up to approximately 3 years
Secondary	Overall survival in participants with brain metastases at baseline (OS.BM)	OS.BM is defined as the time from randomization to death due to any cause in participants with brain metastases at baseline.	Up to approximately 5 years
Secondary	Duration of response (DOR) per RECIST v1.1 by investigator assessment	DOR is defined as the time from first documentation of objective response (CR or PR that is subsequently confirmed) to the first documentation of disease progression or death from any cause, whichever occurs earlier.	Up to approximately 5 years
Secondary	DOR per RECIST v1.1 by BICR		Up to approximately 5 years
Secondary	Clinical benefit rate (CBR) per RECIST v1.1 by investigator assessment	CBR is defined as the proportion of participants with stable disease (SD) or non-CR or non-PD for =6 months or best response of CR or PR according to RECIST v1.1.	Up to approximately 3 years
Secondary	CBR per RECIST v1.1 by BICR		Up to approximately 3 years
Secondary	Number of participants with adverse events (AEs)	An AE is any untoward medical occurrence in a subject or clinical investigational subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment.	Through 1 month following last dose; up to approximately 9 months overall per participant