Zimberelimab and Domvanalimab in Combination With Chemoth... | NCT05502237

NCT05502237

ID	Type	Description	Link
2022-000578-25	EudraCT Number

Status Module

Name	Class
Arcus Biosciences, Inc.	INDUSTRY

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Zimberelimab (ZIM) +Domvanalimab (DOM) + Chemotherapy	Experimental	Participants will receive ZIM 360 mg + DOM 1200 mg (up to 35 doses) with chemotherapy every 3 weeks (Q3W) on Day 1 of each 21-day cycle. Choice of chemotherapy is dependent on histology. Participants with nonsquamous histology will receive cisplatin 75 mg/m^2 or carboplatin area under the concentration versus time curve (AUC)5 + pemetrexed 500 mg/m^2 Q3W for first 4 cycles. After the completion of the first 4 cycles, participants with nonsquamous histology may continue with maintenance pemetrexed 500 mg/m^2 Q3W until disease progression or intolerable toxicities. Participants with squamous histology will receive carboplatin AUC 6 Q3W with paclitaxel 200 mg/m^2 Q3W or nab-paclitaxel 100 mg/m^2 weekly (QW) for first 4 cycles.	Drug: Zimberelimab Drug: Domvanalimab Drug: Carboplatin Drug: Cisplatin Drug: Paclitaxel Drug: Nab-paclitaxel Drug: Pemetrexed
Pembrolizumab (PEMBRO) + Chemotherapy	Active Comparator	Participants will receive PEMBRO 200 mg (up to 35 doses) with chemotherapy Q3W on Day 1 of each 21-day cycle. Choice of chemotherapy is dependent on histology. Participants with nonsquamous histology will receive cisplatin 75 mg/m^2 or carboplatin AUC 5 + pemetrexed 500 mg/m^2 Q3W for first 4 cycles. After the completion of the first 4 cycles, participants with nonsquamous histology may continue with maintenance pemetrexed 500 mg/m^2 Q3W until disease progression or intolerable toxicities. Participants with squamous histology will receive carboplatin AUC 6 Q3W with paclitaxel 200 mg/m^2 Q3W or nab-paclitaxel 100 mg/m^2 weekly (QW) for first 4 cycles.	Drug: Pembrolizumab Drug: Carboplatin Drug: Cisplatin Drug: Paclitaxel Drug: Nab-paclitaxel Drug: Pemetrexed
Zimberelimab (ZIM) + Chemotherapy	Experimental

Name	Type	Description	Arm Group Labels	Other Names
Zimberelimab	Drug	Administered intravenously	Zimberelimab (ZIM) + Chemotherapy Zimberelimab (ZIM) +Domvanalimab (DOM) + Chemotherapy

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Overall Survival (OS) in Participants With Positive Programmed Cell Death-Ligand 1 (PD-L1) Expression (≥1%Tumor Cells) and in all Randomized Participants.	OS is defined as the time from the date of randomization to the date of death from any cause.	Up to 68 months

Secondary Outcomes

Measure	Description	Time Frame
Progression-free Survival (PFS) as Assessed by Blinded Independent Central Review (BICR) per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1	PFS is defined as the time from the date of randomization until disease progression (PD) or death from any cause, whichever comes first.	Upt to 50 months

Eligibility Module

Eligibility 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/Exclusion criteria may apply.

Name	Affiliation	Role
Gilead Study Director	Gilead Sciences	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Innovative Clinical Research Institute		Whittier	California	90606	United States
George Washington Medical Faculty Associates

Label	URL
Gilead Clinical Trials Website	View source

Ancestor Terms

ID	Term
D056831	Coordination Complexes
D009930	Organic Chemicals
D017606	Chlorine Compounds
D007287	Inorganic Chemicals
D017672	Nitrogen Compounds
D017671	Platinum Compounds
D043823	Taxoids
D043822	Cyclodecanes
D003516	Cycloparaffins
D006840	Hydrocarbons, Alicyclic
D006844	Hydrocarbons, Cyclic
D006838	Hydrocarbons
D004224	Diterpenes
D013729	Terpenes
D006147	Guanine
D007042	Hypoxanthines
D011688	Purinones
D011687	Purines
D006574	Heterocyclic Compounds, 2-Ring
D000072471	Heterocyclic Compounds, Fused-Ring
D006571	Heterocyclic Compounds
D005971	Glutamates
D024342	Amino Acids, Acidic
D000596	Amino Acids
D000602	Amino Acids, Peptides, and Proteins
D000600	Amino Acids, Dicarboxylic

ID	Term
D002283	Carcinoma, Bronchogenic
D001984	Bronchial Neoplasms
D008175	Lung Neoplasms
D012142	Respiratory Tract Neoplasms
D013899	Thoracic Neoplasms
D009371	Neoplasms by Site
D009369	Neoplasms
D008171	Lung Diseases
D012140	Respiratory Tract Diseases

ID	Term
C000719848	zimberelimab
C582435	pembrolizumab
D016190	Carboplatin
D002945	Cisplatin
D017239	Paclitaxel
C520255	130-nm albumin-bound paclitaxel
D000068437	Pemetrexed