Zimberelimab and Domvanalimab in Combination With Chemotherapy Versus Pembrolizumab With Chemotherapy in Patients With Untreated Metastatic Non-Small Cell Lung Cancer (STAR-121)

A Randomized, Open-Label, Phase 3 Study to Evaluate Zimberelimab and Domvanalimab in Combination With Chemotherapy Versus Pembrolizumab With Chemotherapy for the First-Line Treatment of Patients With Metastatic Non-Small Cell Lung Cancer With No Epidermal Growth Factor Receptor or Anaplastic Lymphoma Kinase Genomic Tumor Aberrations

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Non-small Cell Lung Cancer
• Intervention / Treatment: Drug: Paclitaxel; Drug: Carboplatin; Drug: Zimberelimab; Drug: Domvanalimab; Drug: Pembrolizumab; Drug: Cisplatin; Drug: Pemetrexed; Drug: Nab-paclitaxel

• Study Type: Interventional
• Enrollment (Actual): 1021
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Capital, Argentina, F5300COE
    • Investigaciones CORI S.R.L.
  • Cardoba, Argentina, X5008HHW
    • Centro Médico Privado Centro de Especialidades Médicas Ambulatorias e Investigación Clínica
  • Córdoba, Argentina, 5000
    • Sanatorio Allende
  • Rosario, Argentina, 2000
    • Sanatorio Britanico de Rosario
  • Rosario, Argentina, S2000DSV
    • Sanatorio Parque de Rosario
  • Rosario, Argentina, S2002KDS
    • Hospital Provincial del Centenario
  • Rosario, Argentina, S2013DTC
    • Instituto Medico de La Fundacion Estudios Clinicos
  • Viedma, Argentina, 8500
    • Clínica Viedma
• Austria
  • Linz, Austria, 4020
    • Ordensklinikum Linz Gmbh, Elisabethinen
  • Vienna, Austria, A-1140
    • Krankenhaus Nord - Klinik Floridsdorf
  • Wels, Austria, 4600
    • Klinikum Wels-Grieskirchen
• Belgium
  • Aalst, Belgium, 9300
    • Algemeen Ziekenhuis Sint-Lucas
  • Charleroi, Belgium, 6000
    • Grand Hopital de Charleroi asbl (GHdC)
  • Mechelen, Belgium, 2800
    • Az Sint-Maarten
  • Namur, Belgium, 5000
    • CHU UCL Namur / Site Sainte Elisabeth
• Brazil
  • Belo Horizonte, Brazil, 30130-090
    • Cenantron Centro Avançado de Tratamento Oncologico Ltda
  • Cachoeiro de Itapemirim, Brazil, 29308-014
    • Hospital Evangélico de Cachoeiro de Itapemirim
  • Caxias do Sul, Brazil, 95070-560
    • Fundacao Universidade De Caxias Do Sul - FUCS/RS
  • Fortaleza, Brazil, 60430-230
    • Instituto do Cancer do Ceara - ICC
  • Ijuí, Brazil, 98700-000
    • Oncosite - Centro de Pesquisa Clínica em Oncologia Ltda
  • Porto Alegre, Brazil, 90610-000
    • Hospital São Lucas da PUCRS
  • Porto Alegre, Brazil, 90035-903
    • Hospital de Clinicas de Porto Alegre
  • Porto Alegre, Brazil, 90020-090
    • Irmandade Da Santa Casa de Misericordia de Porto Alegre
  • Santa Cruz do Sul, Brazil, 96810-110
    • Hospital Ana Nery Santa Cruz do Sul
  • São Paulo, Brazil, 03102002
    • Instituto Brasiliero de Controle do Cancer IBCC
  • São Paulo, Brazil, 17210080
    • Centro Des Pesquisas Clinicas da Fundacao Doutor Amaral Carvalho
• Canada
  • Greenfield Park, Canada, J4V 2H1
    • Centre Integre de Sante Et de Services Sociaux de La Monteregie Centre
  • Moncton, Canada, E1C 6Z8
    • Moncton Hospital
  • Québec, Canada, J7Z 2V4
    • CISSS des Laurentides
  • Rimouski, Canada, G5L5T1
    • Centre de santé et services sociaux de Rimouski-Neigette
• Chile
  • Las Condes, Chile, 7550000
    • Clínica Alemana de Santiago
  • Port Montt, Chile, 5500243
    • Clínica Puerto Montt
  • Providencia, Chile, 7500006
    • Orlandioncologia
  • Providencia, Chile, 7510035
    • Oncovida- Santiago
  • Santiago, Chile, 8331143
    • Biocinetic
  • Temuco, Chile, 4800827
    • James Lind Centro de Investigacion del Cancer
  • Viña del Mar, Chile, 2520612
    • Oncocentro Apys
• China
  • Chengdu, China, 610041
    • West China Hospital Sichuan University
  • Chongqing, China, 400030
    • Chongqing University Cancer Hospital
  • Deyang, China, 618000
    • Deyang People's Hospital
  • Fuzhou, China, 350014
    • Fujian Cancer Hospital
  • Guangzhou, China, 510120
    • The First Affiliated Hospital of Guangzhou Medical University
  • Guangzhou, China, 510180
    • Guangzhou First People's Hospital
  • Hangzhou, China, 310005
    • Zhejiang Cancer Hospital
  • Jiangxi, China, 330006
    • The Second Affiliated Hospital of Nanchang University
  • Jinan, China, 250021
    • Shandong Cancer Hospital
  • Nanchang, China, 330006
    • Jiangxi Chest Hospital
  • Nanjing, China, 210008
    • Nanjing Drum Tower Hospital
  • Nanning, China, 530021
    • Guangxi Medical University Cancer Hospital
  • Shanghai, China, 200030
    • Shanghai Chest Hospital
  • Shanghai, China, 200433
    • Shanghai Pulmonary Hospital
  • Shanghai, China, 200120
    • Shanghai East Hospital
  • Shantou, China, 0754-88555844
    • Cancer Hospital of Shantou University Medical College
  • Tianjin, China, 300181
    • Tianjin Medical University Cancer Institute & Hospital
  • Wuhan, China, 430022
    • Union Hospital Tongji Medical College Huazhong University of Science and Technology
  • Wuhan, China, 430030
    • Tongji Hospital Tongji Medical College Of Hust
  • Xi'an, China, 710049
    • The First Affiliated Hospital of Xian Jiaotong University
  • Xinxiang, China, 453100
    • The First Affiliated Hospital of Xinxiang Medical College
  • Zhengzhou, China, 450008
    • Henan Cancer Hospital
• France
  • Boulogne-Billancourt, France, 92100
    • Ambroise-Pare Hospital, Assistance Publique - Hopitaux de Paris
  • Le Mans, France, 72000
    • Clinique Victor Hugo, Centre de Cancerologie de la Sarthe
  • Marseille, France, 13005
    • Hopital Nord
  • Montpellier, France, 34928
    • Institut de Cancer de Montpellier (ICM) - Val d'Aurelle
  • Saint-Herblain, France, 44805
    • Institut de Cancérologie de l'Ouest (ICO)
  • Saint-Mandé, France, 94160
    • Hopital d'Instruction Des Armees (HIA) Begin
  • Saint-Quentin, France, 2100
    • Centre Hospitalier de Saint-Quentin
  • Suresnes, France, 92150
    • Hopital Foch
  • Toulon, France, 83056
    • CHI de Toulon la Seyne-sur-Mer Hopital Sainte Musse
• Germany
  • Cologne, Germany, 51109
    • Kliniken der Stadt Köln ggmbh, Krankenhaus Koln-Merheim/Lungenklinik
  • Essen, Germany, 45122
    • Universitatsklinikum Essen / Westdeutsches Tumorzentrum, Innere Klinik (Tumorforschung)
  • Großhansdorf, Germany, 22927
    • LungenClinic Grosshansdorf
  • Halle, Germany, 06120
    • Krankenhaus Martha-Maria Halle Dölau
  • Hamburg, Germany, 22087
    • Katholisches Marienkrankenhaus gGmbH
  • Hamburg, Germany, 21075
    • Asklepios Kliniken Hamburg
  • Hemer, Germany, 58675
    • Lungenklinik Hemer, Zentrum fur Pneumologie and Thoraxchirurgie
  • Karlsruhe, Germany, 76137
    • Vincentius-Diakonissen-Kliniken gAG, St. Vincentius-Kliniken, Medizinische Klinik 2
  • Lübeck, Germany, 23538
    • Universitätsklinikum Schleswig-Holstein
  • Minden, Germany, 32429
    • Johannes Wesling Klinikum Minden
  • Offenbach, Germany, 63069
    • Sana Klinikum Offenbach GmbH, Medizinische Klinik IV, Hämatologie und Internistische Onkologie
• Hong Kong
  • Hong Kong, Hong Kong, 999077
    • Queen Mary Hospital
  • Hong Kong, Hong Kong, 999077
    • Queen Elizabeth Hospital
  • New Territories, Hong Kong
    • Prince of Wales Hospital
• Israel
  • Jerusalem, Israel, 9103102
    • Shaare Zedek Medical Center
  • Nahariya, Israel
    • Oncology Institute, Galilee Medical Center, Route 89 Nahariya-Cabri
  • Petah Tikva, Israel, 49100
    • Rabin Medical Center
  • Tel Aviv, Israel, 64239
    • Tel-Aviv Sourasky Medical Center
• Italy
  • Avellino, Italy
    • Azienda Ospedaliera San Giuseppe Moscati
  • Cremona, Italy, 26100
    • Azienda Socio Sanitaria Territoriale di Cremona
  • Genova, Italy, 16132
    • Ospedale Policlinico San Martino
  • Milan, Italy, 20132
    • Ospedale San Raffaele
  • Naples, Italy, 80131
    • AORN Cardarelli
  • Pavia, Italy, 27100
    • IRCCS Policlinico S. Matteo, Dipartimento Oncologia Ematologia-Oncologia Medica
  • Pesaro, Italy, 61122
    • Azienda Sanitaria Territoriale Pesaro e Urbino (AST)
  • Piacenza, Italy, 29100
    • Ospedale Guglielmo da Saliceto AUSL di Piacenza
  • Pordenone, Italy, 33081
    • Centro di riferimento Oncologico
  • Rome, Italy, 00144
    • Regina Elena Institute for Cancer Research
• Japan
  • Chiba, Japan, 277-0882
    • National Cancer Center Hospital East
  • Ehime, Japan, 791-0280
    • National Hospital Organization Shikoku Cancer Center
  • Fukuoka, Japan, 812-8582
    • Kyushu University Hospital
  • Fukuoka, Japan, 830-0011
    • Kurume University Hospital
  • Hyōgo, Japan, 670-8520
    • National Hospital Organization Himeji Medical Center
  • Hyōgo, Japan, 673-8558
    • Hyogo Cancer Center
  • Ishikawa, Japan, 920-8641
    • Kanazawa University Hospital
  • Kanagawa, Japan, 241-0815
    • Kanagawa Cancer Center
  • Miyagi, Japan, 981-0914
    • Sendai Kousei Hospital
  • Niigata, Japan, 951-8566
    • Niigata Cancer Center Hospital
  • Osaka, Japan, 589-8511
    • Kindai University Hospital
  • Osaka, Japan, 545-8586
    • Osaka Metropolitan University Hospital
  • Osaka, Japan, 569-8686
    • Osaka Medical and Pharmaceutical University Hospital
  • Osaka, Japan, 591-8555
    • National Hospital Organization Kinki Chuo Chest Medical Center
  • Saitama, Japan, 350-1298
    • Saitama Medical University
• Mexico
  • Mitras Centro, Mexico, 64460
    • Hospital Universitario Dr. Jose Eleuterio González
  • México, Mexico, 3100
    • Health Pharma Professional Research S.A. de C.V.
  • Oaxaca City, Mexico, 68020
    • Centro de Investigacion Clinica de Oaxaca
  • Oaxaca City, Mexico, 68000
    • Oaxaca Site Management Organization
  • Orizaba Centro, Mexico, 94300
    • Clinical Medical Research SC.
  • Puebla City, Mexico, 72530
    • Clínica Integral Internacional de Oncología S de RL de CV
  • Veracruz, Mexico, 91900
    • FAICIC Clínical Research
• Netherlands
  • Breda, Netherlands, 4818 CK
    • Amphia Ziekenhuis
  • Ede, Netherlands, 6716 RP
    • Ziekenhuis Gelderse Vallei
  • Groningen, Netherlands, 9713 GZ
    • Universitair Medisch Centrum Groningen
  • Harderwijk, Netherlands, 3844 DG
    • Ziekenhuis St Jansdal
  • Tilburg, Netherlands
    • TweeSteden Ziekenhuis
• Portugal
  • Amadora, Portugal, 2720276
    • Hospital Prof. Doutor Fernando Fonseca
  • Lisbon, Portugal, 1400-038
    • Fundacao Champalimaud
  • Lisbon, Portugal, 2674-514
    • Hospital Beatriz Angelo. Hospital de Loures.
  • Lisbon, Portugal, 1089
    • Instituto Portugues De Oncologia De Lisboa Francisco Gentil
  • Lisbon, Portugal
    • Centro Hospitalar Universitário Lisboa Norte - Hospital Pulido Valente
  • Senhora da Hora, Portugal, 4464-513
    • Unidade Local de Saude de Matosinhos EPE - Hospital Pedro Hispano SA
• Singapore
  • Singapore, Singapore, 308433
    • Tang Tock Seng Hospital
• South Korea
  • Gangnam-Gu, South Korea, 6351
    • Samsung Medical Center
  • Goyang, South Korea, 410769
    • National Cancer Center
  • Heungdeok-Gu, South Korea, 361-711
    • Chungbuk National University Hospital
  • Inchon, South Korea, 21565
    • Gachon University Gil Medical Center
  • Seoul, South Korea, 03722
    • Severance Hospital, Yonsei University Health System
  • Seoul, South Korea, 06591
    • The Catholic University of Korea, Seoul St. Mary's Hospital
  • Suwon, South Korea, 16247
    • The Catholic University of Korea, Saint Vincent's Hospital
• Spain
  • Barcelona, Spain, 08036
    • Hospital Clínic de Barcelona
  • Barcelona, Spain, 8035
    • Hospital Universitari Vall d'Hebron
  • Barcelona, Spain, 08041
    • Hospital de la Santa Creu i de Sant Pau
  • Barcelona, Spain, 8028
    • Hospital Universitari Dexeus (USP Institut Universitari Dexeus/Hospital Universitari Quiron Dexeus)
  • Barcelona, Spain, 8208
    • Hospital Parc Tauli
  • Córdoba, Spain, 14004
    • Hospital Universitario Reina Sofia
  • Girona, Spain, 17007
    • Hospital Doctor Josep Trueta
  • Jaén, Spain, 23007
    • Hospital Universitario de Jaén
  • Las Palmas de Gran Canaria, Spain, 35016
    • Hospital Universitario de Canarias
  • Madrid, Spain, 28046
    • Hospital Universitario La Paz
  • Madrid, Spain, 28027
    • Clínica Universidad de Navarra
  • Madrid, Spain, 28020
    • Hospital Universitario Fundacion Jimenez Diaz
  • Majadahonda, Spain, 28222
    • Hospital Universitario Puerta de Hierro de Majadahonda
  • Reus, Spain, 43204
    • Hospital Sant Joan de Reus
  • Rincón de la Victoria, Spain, 29011
    • Hospital Regional Universitario de Málaga
  • Seville, Spain, 41009
    • Hospital Universitario Virgen Macarena
  • Seville, Spain, 41014
    • Hospital Universitario Virgen Del Rocio
  • Valencia, Spain, 46009
    • Instituto Valenciano de Oncología (IVO)
  • Valencia, Spain, 46015
    • Hospital Universitari i Politècnic La Fe
  • Valencia, Spain, 46015
    • Hospital Vithas Valencia 9 de octubre
• Taiwan
  • Changhua, Taiwan, 500-06
    • Changhua Christian Hospital
  • Kaohsiung City, Taiwan, 807
    • Kaohsiung Medical University Chung-Ho Memorial Hospital
  • Kaohsiung City, Taiwan, 824
    • E-DA Hospital
  • Kaohsiung City, Taiwan, 83301
    • Chang Gung Memorial Hospital Kaohsiung
  • Tainan, Taiwan, 736
    • Chi Mei Hospital, Liouying
  • Taipei, Taiwan, 100
    • National Taiwan University Hospital
  • Taipei, Taiwan, 10002
    • Taipei Veterans General Hospital
  • Taoyuan, Taiwan, 33305
    • Chang Gung Memorial Hospital Linkou Branch of the Chang Gung Medical Foundation
• Turkey (Türkiye)
  • Ankara, Turkey (Türkiye), 06550
    • Ankara Bilkent Sehir Hastanesi
  • Ankara, Turkey (Türkiye), 6200
    • Dr. Abdurrahman Yurtaslan Ankara Onkoloji Egitim ve Arastirma Hastanesi
  • Edirne, Turkey (Türkiye), 22030
    • Trakya University Faculty of Medicine
  • Fatih, Turkey (Türkiye), 34098
    • Istanbul University Cerrahpasa Medical Faculty Hospital
  • Istanbul, Turkey (Türkiye), 34093
    • Goztepe Prof. Dr. Suleyman Yalcın Sehir Hastanesi
  • Istanbul, Turkey (Türkiye)
    • Medipol Mega University Hospital
  • Kaakaekmece, Turkey (Türkiye), 34303
    • Acibadem Mehmet Ali Aydinlar Universitesi Atakent Hastanesi
  • Malatya, Turkey (Türkiye), 44300
    • Turgut Ozal Medical Faculty
• United Kingdom
  • London, United Kingdom, EC1A 7BE
    • St Bartholomew's Hospital, Barts Health NHS Trust
  • Manchester, United Kingdom, M20 4BX
    • The Christie NHS Foundation Trust, Department of Medical Oncology
• United States
  • California
    • Whittier, California, United States, 90606
      • Innovative Clinical Research Institute
  • District of Columbia
    • Washington D.C., District of Columbia, United States, 20052
      • George Washington Medical Faculty Associates
  • Florida
    • Tampa, Florida, United States, 33612
      • Moffitt Cancer Center
  • Illinois
    • Peoria, Illinois, United States, 61615
      • Illinois Cancer Care
  • North Carolina
    • Asheville, North Carolina, United States, 28806
      • Messino Cancer Centers
  • Ohio
    • Cincinnati, Ohio, United States, 45242
      • Oncology Hematology Care, Inc.
  • Oregon
    • Eugene, Oregon, United States, 97401
      • Hematology & Oncology Associates
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15212
      • AHN Allegheny General Hospital
  • Texas
    • Austin, Texas, United States, 78745
      • Texas Oncology - Austin
  • Virginia
    • Blacksburg, Virginia, United States, 24060
      • Oncology and Hematology Associates of Southwest Virginia, Inc
  • Washington
    • Vancouver, Washington, United States, 98684
      • Northwest Cancer Specialists, PC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Zimberelimab (ZIM) +Domvanalimab (DOM) + Chemotherapy; 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: Paclitaxel; Administered intravenously; Drug: Carboplatin; Administered intravenously; Drug: Zimberelimab; Administered intravenously; Other Names: AB122; GS-0122; Drug: Domvanalimab; Administered intravenously; Other Names: AB154; GS-0154; Drug: Cisplatin; Administered intravenously; Drug: Pemetrexed; Administered intravenously; Drug: Nab-paclitaxel; Administered intravenously
Active Comparator: Pembrolizumab (PEMBRO) + Chemotherapy; 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: Paclitaxel; Administered intravenously; Drug: Carboplatin; Administered intravenously; Drug: Pembrolizumab; Administered intravenously; Other Names: KEYTRUDA®; Drug: Cisplatin; Administered intravenously; Drug: Pemetrexed; Administered intravenously; Drug: Nab-paclitaxel; Administered intravenously
Experimental: Zimberelimab (ZIM) + Chemotherapy; Participants will receive ZIM 360 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: Paclitaxel; Administered intravenously; Drug: Carboplatin; Administered intravenously; Drug: Zimberelimab; Administered intravenously; Other Names: AB122; GS-0122; Drug: Cisplatin; Administered intravenously; Drug: Pemetrexed; Administered intravenously; Drug: Nab-paclitaxel; Administered intravenously

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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 Outcome Measures

Outcome Measure	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
Objective Response Rate (ORR) as Assessed by BICR per RECIST Version 1.1	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.	Up to 50 Months
Duration of Response (DOR) as Assessed by BICR per RECIST Version 1.1	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.	Up to 50 Months
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	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.	Baseline, Up to 50 Months

Collaborators and Investigators

• Sponsor: Gilead Sciences
• Collaborators: Arcus Biosciences, Inc.
• Investigators: Study Director: Gilead Study Director, Gilead Sciences

Publications and helpful links

Helpful Links

• Gilead Clinical Trials Website

Study record dates

Study Major Dates

• Study Start (Actual): October 12, 2022
• Primary Completion (Estimated): June 1, 2028
• Study Completion (Estimated): January 1, 2029

Study Registration Dates

• First Submitted: August 12, 2022
• First Submitted That Met QC Criteria: August 12, 2022
• First Posted (Actual): August 16, 2022

Study Record Updates

• Last Update Posted (Actual): January 30, 2026
• Last Update Submitted That Met QC Criteria: January 28, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Carcinoma, Non-Small-Cell Lung; Amino Acids, Peptides, and Proteins; Organic Chemicals; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Hydrocarbons; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Terpenes; Inorganic Chemicals; Chlorine Compounds; Nitrogen Compounds; Coordination Complexes; Guanine; Hypoxanthines; Purinones; Purines; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Dicarboxylic; Taxoids; Cyclodecanes; Diterpenes; Platinum Compounds; Pemetrexed; Carboplatin; Paclitaxel; Cisplatin; pembrolizumab; 130-nm albumin-bound paclitaxel; zimberelimab
• Other Study ID Numbers: GS-US-626-6216; 2022-000578-25 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No