Study to Evaluate Monotherapy and Combination Immunotherapies in Participants With PD-L1 Positive Non-small Cell Lung Cancer
- Conditions
- Squamous Non Small Cell Lung CancerNon Small Cell Lung CancerLung CancerNonsquamous Non Small Cell Lung Cancer
- Interventions
- Registration Number
- NCT04262856
- Lead Sponsor
- Arcus Biosciences, Inc.
- Brief 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 151
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm 3 (domvanalimab, etrumadenant, and zimberelimab combination therapy) Zimberelimab Participants will receive oral etrumadenant in combination with domvanalimab IV and zimberelimab IV infusion Arm 3 (domvanalimab, etrumadenant, and zimberelimab combination therapy) Domvanalimab Participants will receive oral etrumadenant in combination with domvanalimab IV and zimberelimab IV infusion Arm 2 (domvanalimab and zimberelimab combination therapy) Domvanalimab Participants will receive domvanalimab IV in combination with zimberelimab IV infusion. Arm 2 (domvanalimab and zimberelimab combination therapy) Zimberelimab Participants will receive domvanalimab IV in combination with zimberelimab IV infusion. Arm 1 (zimberelimab monotherapy) Zimberelimab Participants will receive zimberelimab as an intravenous (IV) infusion. Arm 3 (domvanalimab, etrumadenant, and zimberelimab combination therapy) Etrumadenant Participants will receive oral etrumadenant in combination with domvanalimab IV and zimberelimab IV infusion
- Primary Outcome Measures
Name Time Method Objective response rate (ORR) From randomization until death from any cause (up to approximately 3-5 years) ORR as assessed by RECIST v1.1
Progression-free survival (PFS) From randomization until death from any cause (up to approximately 3-5 years) PFS as assessed by RECIST v1.1
- Secondary Outcome Measures
Name Time Method Duration of response (DoR) 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) DoR as assessed by RECIST v1.1
Pharmacokinetics of zimberelimab 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) Serum concentration of zimberelimab as determined by validated assays
Pharmacokinetics of domvanalimab 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) Serum concentration of domvanalimab as determined by validated assays
Disease control rate (DCR) 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) DCR as assessed by RECIST v1.1
Number of Participants with Treatment Emergent Adverse Events (TEAEs) From Screening until up to 30 days after the last dose (approximately 5 years) The number and percentage of participants that experience TEAE
Pharmacokinetics of etrumadenant 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) Serum concentration of etrumadenant as determined by validated assays
Immunogenicity of 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). Percentage of participants who develop treatment-emergent anti-drug antibodies to zimberelimab
Immunogenicity of 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). Percentage of participants who develop treatment-emergent anti-drug antibodies to domvanalimab
Overall Survival (OS) From randomization to death from any cause (up to approximately 5 years) OS as assessed at the time of PFS
Trial Locations
- Locations (43)
Kangbuk Samsung Hospital
🇰🇷Seoul, Korea, Republic of
Chi Mei Hospital
🇨🇳Tainan City, Taiwan
Chungbuk National University Hospital (CBNUH)
🇰🇷Cheongju, Korea, Republic of
University of Alabama at Birmingham
🇺🇸Birmingham, Alabama, United States
Innovative Clinical Research Institute (ICRI)
🇺🇸Whittier, California, United States
Florida Cancer Specialists
🇺🇸Gainesville, Florida, United States
Florida Cancer Specialists - Panhandle
🇺🇸Tallahassee, Florida, United States
Florida Cancer Specialists - East
🇺🇸West Palm Beach, Florida, United States
Baptist Health Lexington
🇺🇸Lexington, Kentucky, United States
Norton Cancer Institute
🇺🇸Louisville, Kentucky, United States
Ochsner Clinic Foundation
🇺🇸New Orleans, Louisiana, United States
The Valley Hospital - Valley Health System - The Robert and Audrey Luckow Pavilion
🇺🇸Ridgewood, New Jersey, United States
Clinical Research Alliance
🇺🇸Lake Success, New York, United States
Northwell Health Cancer Institute
🇺🇸Lake Success, New York, United States
Wake Forest Baptist Health
🇺🇸Winston-Salem, North Carolina, United States
Allegheny General Hospital (AGH)-Alleghney Singer Research Institute
🇺🇸Pittsburgh, Pennsylvania, United States
Sarah Cannon Research Institute
🇺🇸Nashville, Tennessee, United States
The Center For Cancer And Blood Disorders (Texas Cancer Care)
🇺🇸Fort Worth, Texas, United States
Millennium Oncology
🇺🇸Houston, Texas, United States
Oncology and Hematology Associates of Southwest Virginia, Inc., DBA Blue Ridge Cancer Care
🇺🇸Blacksburg, Virginia, United States
Virginia Cancer Specialists
🇺🇸Fairfax, Virginia, United States
Border Medical Oncology
🇦🇺Albury, Australia
Coffs Harbour Health Campus
🇦🇺Coffs Harbour, Australia
Adelaide Cancer Centre
🇦🇺Elizabeth Vale, Australia
Shoalhaven Cancer Care Centre
🇦🇺Nowra, Australia
McGill University Health Centre (MUHC) - The Montreal Children's Hospital (MCH)
🇨🇦Montreal, Canada
Hong Kong United Oncology Centre
🇭🇰Hong Kong, Hong Kong
Queen Elizabeth Hospital (Hong Kong)
🇭🇰Hong Kong, Hong Kong
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
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, Korea, Republic of
Curie Oncology
🇸🇬Singapore, Singapore
Taipei Medical University - Shuang Ho Hospital
🇨🇳New Taipei, Taiwan
National Cheng Kung University Hospital
🇨🇳Tainan, Taiwan
National Taiwan University Hospital
🇨🇳Taipei, Taiwan
Taipei Medical University Hospital
🇨🇳Taipei, Taiwan
Chang Gung Memorial Hospital at Linkou
🇨🇳Taoyuan, Taiwan