Non-small Cell Lung Cancer
Conditions
Brief summary
The primary objective of this study is to compare the effect of zimberelimab (ZIM) and domvanalimab (DOM) in combination with chemotherapy relative to pembrolizumab (PEMBRO) in combination with chemotherapy on overall survival (OS) in patients with untreated metastatic non-small cell lung cancer with no actionable genomic alteration.
Interventions
DRUGNab-paclitaxel
Administered intravenously
DRUGPemetrexed
Administered intravenously
DRUGZimberelimab
Administered intravenously
DRUGDomvanalimab
Administered intravenously
DRUGPembrolizumab
Administered intravenously
DRUGCarboplatin
Administered intravenously
DRUGCisplatin
Administered intravenously
DRUGPaclitaxel
Administered intravenously
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
Key Inclusion Criteria: * Life expectancy ≥ 3 months. * Pathologically documented NSCLC that meets both of the criteria below: * Have documented evidence of Stage IV NSCLC disease at the time of enrollment (based on American Joint Committee on Cancer (AJCC), Eighth Edition). * Have documented negative test results for epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) mutations. * Have no actionable genomic alterations such as ROS proto-oncogene 1 (ROS1), neurotrophic tyrosine receptor kinase (NTRK), proto-oncogene B-raf (BRAF), RET mutations, or other driver oncogenes with approved frontline therapies. * Have not received prior systemic treatment for metastatic NSCLC. * Measurable disease per RECIST v1.1 criteria by investigator assessment. * Eastern Cooperative Oncology Group performance status (ECOG PS) score of 0 or 1. * Have adequate organ functions. Key
Exclusion criteria
* Have mixed small-cell lung cancer (SCLC) and NSCLC histology. * Positive serum pregnancy test or individuals who are breastfeeding or have plans to breastfeed during the study period. * Received prior treatment with any anti-PD-1, anti-PD-L1, or any other antibody targeting an immune checkpoint. * Known hypersensitivity to the study drug, its metabolites, or formulation excipient. * Have an active second malignancy or have had an active second malignancy within 3 years prior to enrollment. * Have an active autoimmune disease that required systemic treatment in past 2 years (i.e., with use of disease-modifying agents, corticosteroids, or immunosuppressive drugs). * Are receiving chronic systemic steroids. * Have significant third-space fluid retention. * Have untreated central nervous system (CNS) metastases and/or carcinomatous meningitis. * Active chronic inflammatory bowel disease (ulcerative colitis, Crohn's disease) or gastrointestinal perforation within 6 months of enrollment. * Has a history of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease. * Has had an allogenic tissue/solid organ transplant. * Have received a live-virus vaccination within 30 days of planned treatment start. Seasonal flu and COVID-19 vaccines that do not contain live virus are permitted. * Have known active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection. Note: Other protocol defined Inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) in Participants With Positive Programmed Cell Death-Ligand 1 (PD-L1) Expression (≥1%Tumor Cells) and in all Randomized Participants. | Up to 68 months | OS is defined as the time from the date of randomization to the date of death from any cause. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free Survival (PFS) as Assessed by Blinded Independent Central Review (BICR) per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 | Upt to 50 months | PFS is defined as the time from the date of randomization until disease progression (PD) or death from any cause, whichever comes first. |
| Objective Response Rate (ORR) as Assessed by BICR per RECIST Version 1.1 | Up to 50 Months | ORR is defined as the proportion of participants who have achieved a complete response (CR) or partial response (PR) that is confirmed at least 4 weeks later. |
| Duration of Response (DOR) as Assessed by BICR per RECIST Version 1.1 | Up to 50 Months | DOR is defined as the time from the first response (CR or PR), to the first documented PD or death from any cause, whichever comes first. |
| Percentage of Participants Experiencing Treatment-emergent Adverse Events (TEAEs) | First dose date up to 50 months plus 30 days | — |
| Percentage of Participants Experiencing Clinical Laboratory Abnormalities | First dose date up to 50 months plus 30 days | — |
| Time to First Symptom Deterioration in Non-small Cell Lung Cancer Symptom Assessment Questionnaire (NSCLC-SAQ) Total Score | Baseline, Up to 50 Months | The NSCLC-SAQ is a patient reported outcome measure with seven items assessing five symptom concepts of NSCLC: cough, pain, dyspnea, fatigue, and appetite. Each item is rated using a five-point verbal rating scale from "No \<symptom\> At All" to "Very severe \<symptom\>" or from "Never to Always," corresponding to a score of 0 to 4. The sum of all 5 domain scores will be computed, if any scores are missing, a total score will not be computed. The total score ranges between 0 and 20 with higher scores indicating more severe symptoms. |
Countries
Argentina, Austria, Belgium, Brazil, Canada, Chile, China, France, Germany, Hong Kong, Israel, Italy, Japan, Mexico, Netherlands, Portugal, Singapore, South Korea, Spain, Taiwan, Turkey (Türkiye), United Kingdom, United States
Contacts
STUDY_DIRECTORGilead Study Director
Gilead Sciences
Outcome results
None listed