Study to Evaluate Monotherapy and Combination Immunotherapies in Participants With PD-L1 Positive Non-small Cell Lung Cancer

Lung Cancer Clinical Trial

— ARC-7  

Official title:

A Phase 2 Study to Evaluate the Safety and Efficacy of AB122 Monotherapy, AB154 in Combination With AB122, and AB154 in Combination With AB122 and AB928 in Front-Line, Non-Small Cell Lung Cancer

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04262856
• Other study ID #: ARC-7 (AB154CSP0002)
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: May 28, 2020
• Est. completion date: February 2025

Study information

• Verified date: May 2024
• Source: Arcus Biosciences, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This randomized phase 2 open-label study will evaluate the safety and efficacy of zimberelimab (AB122) monotherapy, domvanalimab (AB154) in combination with zimberelimab, and domvanalimab in combination with zimberelimab and etrumadenant (AB928) in front-line, PD-L1 positive, metastatic non-small cell lung cancer.

Description:

This is an open-label phase 2 study in participants with non-small cell lung cancer which will assess the safety, efficacy and tolerability of zimberelimab as monotherapy and in combination with other immunotherapeutics across multiple treatment arms. Approximately 150 participants will be randomized to 1 of 3 treatment arms: 1) zimberelimab, 2) zimberelimab + domvanalimab (anti-TIGIT antibody), 3) zimberelimab + domvanalimab + etrumadenant (dual adenosine receptor antagonist). Participants that progress on the zimberelimab monotherapy arm may cross-over to receive the third arm combination of zimberelimab + domvanalimab + etrumadenant. The primary objective of this clinical study is to evaluate the efficacy of each combination therapy by assessing: 1) objective response rate (ORR) of participants with measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST v1.1) and 2) progression free survival (PFS).

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 151
• Est. completion date: February 2025
• Est. primary completion date: February 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Male or female participants; age = 18 years
• Histologically confirmed, treatment naïve, metastatic squamous or non-squamous NSCLC with documented high PD-L1 expression, with no epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) genomic tumor aberrations.
• Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1
• Must have at least 1 measurable lesion per RECIST v1.1
• Adequate organ and marrow function

Exclusion Criteria:

• Use of any live vaccines against infectious diseases within 28 days of first dose of investigational medicinal products (IMPs)
• Any gastrointestinal condition that would preclude the use of oral medications (eg, difficulty swallowing, nausea, vomiting, or malabsorption)
• History of trauma or major surgery within 28 days prior to the first dose of IMP
• Concurrent medical condition requiring the use of supra-physiologic doses of corticosteroids (> 10 mg/day of oral prednisone or equivalent) or immunosuppressive medications
• Positive test results for Hepatitis B surface antigen, Hepatitis C virus antibody with presence of Hepatitis C qualitative RNA or human immunodeficiency virus (HIV-1 and/or HIV-2) antibody at screening
• Any active autoimmune disease or a documented history of autoimmune disease or syndrome that required systemic treatment in the past 2 years (ie, with use of disease-modifying agents, corticosteroids, or immunosuppressive drugs), except for vitiligo or resolved childhood asthma/atopy.
• Prior malignancy active within the previous 2 years except for locally curable cancers that have been apparently cured, such as basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the cervix, breast, or prostate cancer

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Cancer
• Lung Neoplasms
• Non Small Cell Lung Cancer
• Nonsquamous Non Small Cell Lung Cancer
• Squamous Non Small Cell Lung Cancer

Intervention

Drug:
• Domvanalimab
Domvanalimab is a humanized monoclonal antibody targeting human TIGIT
• Etrumadenant
Etrumadenant is an A2aR and A2bR antagonist
• Zimberelimab
Zimberelimab is a fully human anti-PD-1 monoclonal antibody

Locations

Country	Name	City	State
Australia	Border Medical Oncology	Albury	New South Wales
Australia	Coffs Harbour Health Campus	Coffs Harbour	New South Wales
Australia	Adelaide Cancer Centre	Elizabeth Vale	South Australia
Australia	Shoalhaven Cancer Care Centre	Nowra	New South Wales
Australia	Tweed Hospital	Tweed Heads	New South Wales
Canada	Brampton Civic Hospital (Bch), William Osler Health Centre	Brampton
Canada	McGill University Health Centre (MUHC) - The Montreal Children's Hospital (MCH)	Montréal
Canada	Centre Integre de Sante et de Services Sociaux des Laurentides Hopital regional de Saint-Jerome	Saint Jerome
Hong Kong	Hong Kong United Oncology Centre	Hong Kong
Hong Kong	Humanity and Health Research Center	Hong Kong
Hong Kong	Princess Margaret Hospital	Hong Kong
Hong Kong	Queen Elizabeth Hospital (Hong Kong)	Hong Kong
Korea, Republic of	Kosin University Gospel Hospital	Busan
Korea, Republic of	Chonnam University Hospital	Hwasun
Korea, Republic of	Gachon University Gil Medical Center	Incheon
Korea, Republic of	Chonbuk National University Hospital	Jeonju
Korea, Republic of	Seoul National University Bundang Hospital	Seongnam-si
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Kangbuk Samsung Hospital	Seoul
Korea, Republic of	Korea University Anam Hospital	Seoul
Korea, Republic of	Korea University Anam Hospital	Seoul
Korea, Republic of	St Vincent Hospital of the Catholic University of Korea	Suwon-si
Korea, Republic of	Catholic University of Korea, Uijeongbu St. Mary's Hospital	Uijeongbu
Singapore	Curie Oncology	Singapore
Singapore	Oncocare Cancer Centre	Singapore
Singapore	Raffles Hospital	Singapore
Taiwan	Chang Gung Memorial Hospital	Kaohsiung
Taiwan	Chang Gung Memorial Hospital, Kaohsiung Branch	Kaohsiung City
Taiwan	Taipei Medical University - Shuang Ho Hospital	New Taipei
Taiwan	Chung Shan Medical University Hospital	Taichung City
Taiwan	National Cheng Kung University Hospital	Tainan
Taiwan	Chi Mei Hospital	Tainan City
Taiwan	National Taiwan University Hospital	Taipei
Taiwan	Taipei Medical University Hospital	Taipei
Taiwan	Tri-Service General Hospital	Taipei City
Taiwan	Chang Gung Memorial Hospital at Linkou	Taoyuan
United States	Pacific Cancer Medical Center, Inc	Anaheim	California
United States	American Oncology Partners of Maryland, PA	Bethesda	Maryland
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	Oncology and Hematology Associates of Southwest Virginia, Inc., DBA Blue Ridge Cancer Care	Blacksburg	Virginia
United States	Florida Cancer Specialists	Englewood	Florida
United States	Virginia Cancer Specialists	Fairfax	Virginia
United States	Detroit Clinical Research Center, PC	Farmington Hills	Michigan
United States	The Center For Cancer And Blood Disorders (Texas Cancer Care)	Fort Worth	Texas
United States	Florida Cancer Specialists	Gainesville	Florida
United States	Prisma Health-Upstate	Greenville	South Carolina
United States	Hattiesburg Clinic	Hattiesburg	Mississippi
United States	Dr.John R Waldron, MD Off of	Kingwood	Texas
United States	Clinical Research Alliance	Lake Success	New York
United States	Northwell Health Cancer Institute	Lake Success	New York
United States	Comprehensive Cancer Centers Of Nevada	Las Vegas	Nevada
United States	Baptist Health Lexington	Lexington	Kentucky
United States	Baptist Hospital East	Louisville	Kentucky
United States	Norton Cancer Institute	Louisville	Kentucky
United States	Joe Arrington Cancer Research and Treatment Center	Lubbock	Texas
United States	Sarah Cannon Research Institute	Nashville	Tennessee
United States	Ochsner Clinic Foundation	New Orleans	Louisiana
United States	Allegheny General Hospital (AGH)-Alleghney Singer Research Institute	Pittsburgh	Pennsylvania
United States	The Valley Hospital - Valley Health System - The Robert and Audrey Luckow Pavilion	Ridgewood	New Jersey
United States	Florida Cancer Specialists	Saint Petersburg	Florida
United States	Florida Cancer Specialists - Panhandle	Tallahassee	Florida
United States	Tyler Hematology-Oncology, P.A.	Tyler	Texas
United States	Florida Cancer Specialists - East	West Palm Beach	Florida
United States	Innovative Clinical Research Institute (ICRI)	Whittier	California
United States	Wake Forest Baptist Health	Winston-Salem	North Carolina

Sponsors (2)

Lead Sponsor	Collaborator
Arcus Biosciences, Inc.	Gilead Sciences

Countries where clinical trial is conducted

United States,  Australia,  Canada,  Hong Kong,  Korea, Republic of,  Singapore,  Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Objective response rate (ORR)	ORR as assessed by RECIST v1.1	From randomization until death from any cause (up to approximately 3-5 years)
Primary	Progression-free survival (PFS)	PFS as assessed by RECIST v1.1	From randomization until death from any cause (up to approximately 3-5 years)
Secondary	Duration of response (DoR)	DoR as assessed by RECIST v1.1	From the date of first occurrence of a documented objective response to first documentation of disease progression or death from any cause, whichever occurs first (up to approximately 3-5 years)
Secondary	Disease control rate (DCR)	DCR as assessed by RECIST v1.1	From the date of first occurrence of a documented objective response to first documentation of disease progression on death from any cause, whichever occurs first (up to approximately 3-5 years)
Secondary	Overall Survival (OS)	OS as assessed at the time of PFS	From randomization to death from any cause (up to approximately 5 years)
Secondary	Number of Participants with Treatment Emergent Adverse Events (TEAEs)	The number and percentage of participants that experience TEAE	From Screening until up to 30 days after the last dose (approximately 5 years)
Secondary	Pharmacokinetics of zimberelimab	Serum concentration of zimberelimab as determined by validated assays	Collected during all treatment cycles (each cycle is 21 or 28 days), up to 14 days post last dose, 30, 60 and 100 days post last dose (in total, an average of 2 years)
Secondary	Pharmacokinetics of domvanalimab	Serum concentration of domvanalimab as determined by validated assays	Collected during all treatment cycles (each cycle is 21 or 28 days), up to 14 days post last dose, 30, 60 and 100 days post last dose (in total, an average of 2 years)
Secondary	Pharmacokinetics of etrumadenant	Serum concentration of etrumadenant as determined by validated assays	Collected during all treatment cycles (each cycle is 21 or 28 days), up to 14 days post last dose, 30, 60 and 100 days post last dose (in total, an average of 2 years)
Secondary	Immunogenicity of zimberelimab	Percentage of participants who develop treatment-emergent anti-drug antibodies to zimberelimab	Collected during all treatment cycles (each cycle is 21 or 28 days), up to 14 days post last dose, 30, and 100 days post last dose (in total, an average of 2 years).
Secondary	Immunogenicity of domvanalimab	Percentage of participants who develop treatment-emergent anti-drug antibodies to domvanalimab	Collected during all treatment cycles (each cycle is 21 or 28 days), up to 14 days post last dose, 30, and 100 days post last dose (in total, an average of 2 years).