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 naive, 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 the first documentation of disease progression or death from any cause, whichever occurs first (up to approximately 3-5 years) ORR as assessed by RECIST v1.1
Progression-free survival (PFS) From randomization until the first documentation of disease progression or death from any cause, whichever occurs first (up to approximately 3-5 years) PFS as assessed by RECIST v1.1
- Secondary Outcome Measures
Name Time Method Disease control rate (DCR) 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) DCR as assessed by RECIST v1.1
Overall Survival (OS) From randomization to death from any cause (up to approximately 5 years) OS as assessed at the time of PFS
Number of Participants with Treatment Emergent Adverse Events (TEAEs) From Screening until up to 90-100 days after the last dose (approximately 5 years) The number and percentage of participants that experience TEAE
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
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
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
Trial Locations
- Locations (43)
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
Scroll for more (33 remaining)University of Alabama at Birmingham🇺🇸Birmingham, Alabama, United States