Non Small Cell Lung Cancer, Nonsquamous Non Small Cell Lung Cancer, Squamous Non Small Cell Lung Cancer, Lung Cancer
Conditions
Keywords
Non Small Cell Lung Cancer, Lung Cancer, NSCLC
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.
Interventions
DRUGDomvanalimab
Domvanalimab is a humanized monoclonal antibody targeting human TIGIT
DRUGEtrumadenant
Etrumadenant is an A2aR and A2bR antagonist
DRUGZimberelimab
Zimberelimab is a fully human anti-PD-1 monoclonal antibody
Sponsors
Gilead Sciences
Arcus Biosciences, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 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
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| 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 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 |
| 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 or death from any cause, whichever occurs first (up to approximately 3-5 years) | DCR as assessed by RECIST v1.1 |
Countries
Australia, Canada, Hong Kong, Singapore, South Korea, Taiwan, United States
Outcome results
None listed