Study Comparing the Combination Domvanalimab and Zimberelimab With Pembrolizumab in Untreated Locally Advanced or Metastatic PD-L1-High Non-Small Cell Lung Cancer (ARC-10)

A Phase 3 Study to Evaluate Zimberelimab (AB122) Combined With AB154 in Front-Line, PD-L1-High, Locally Advanced or Metastatic Non-Small Cell Lung Cancer

This is a phase 3 study to evaluate zimberelimab (AB122) combined with domvanalimab (AB154) compared to pembrolizumab in front-line, PD-L1-high, locally advanced or metastatic NSCLC.

Study Overview

• Status: Active, not recruiting
• Conditions: Lung Cancer; Non Small Cell Lung Cancer; Squamous Non Small Cell Lung Cancer; Nonsquamous Non Small Cell Lung Cancer
• Intervention / Treatment: Drug: Zimberelimab; Drug: Domvanalimab; Drug: Carboplatin; Drug: Pemetrexed; Drug: Paclitaxel; Drug: Pembrolizumab

• Study Type: Interventional
• Enrollment (Actual): 169
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Medical Director; Phone Number: +1-510-462-3330; Email: ClinicalTrials@arcusbio.com

Study Locations

• Bangladesh
  • Dhaka, Bangladesh
    • Ahsania Mission Cancer and General Hospital
  • Dhaka, Bangladesh
    • Bangladesh Cancer Society Hospital and Welfare Home
  • Dhaka, Bangladesh
    • Kurmitola General Hospital
• Brazil
  • Barretos, Brazil
    • Hospital de Cancer de Barretos - Fundacao Pio XII
  • Belo Horizonte, Brazil
    • Associação Mário Pena - Núcleo de Ensino e Pesquisas Mário Penna
  • Brasília, Brazil
    • Hospital DF Star
  • Curitiba, Brazil
    • CIONC-Centro Integrado de Oncologia de Curitiba
  • Florianópolis, Brazil
    • CEPON - Centro de Pesquisas Oncológicas de Santa Catarina
  • Ijuí, Brazil
    • Hospital de Caridade de Ijui
  • Jaú, Brazil
    • Fundacao Doutor Amaral Carvalho
  • Passo Fundo, Brazil
    • Instituto Méderi de Pesquisa e Saúde
  • Porto Alegre, Brazil
    • Santiago Escovar, Carlos Eugênio
  • Santa Cruz do Sul, Brazil
    • Instituto de Oncologia Saint Gallen
  • Santo André, Brazil
    • Cepho - Centro de Estudos E Pesquisas de Hematologia E Oncologia
  • São José Do Rio Preto, Brazil
    • Fundacao Faculdade Regional de Medicina de Sao Jose Do Rio Preto
  • São Paulo, Brazil
    • Icesp - Instituto Do Câncer Do Estado de São Paulo Octavio Frias de Oliveira
  • São Paulo, Brazil
    • IBCC - Instituto Brasileiro de Controle do Cancer
• France
  • Boulogne-Billancourt, France
    • Hopital Ambroise Pare
  • Créteil, France
    • Center Hospitalier Intercommunal de creteil
  • Poitiers, France
    • CHU de Poitiers
  • Rennes, France
    • Chu Rennes Hopital Pontchaillou
  • Toulouse, France
    • Hopital Larrey
• Greece
  • Athens, Greece
    • General Hospital of Athens "Alexandra"
  • Athens, Greece
    • University General Hospital "Attikon"
  • Athens, Greece
    • General Hospital of Athens of Chest Diseases "SOTIRIA"
  • Athens, Greece
    • General Oncology Hospital of Kifissia "Agioi Anargyroi"
  • Athens, Greece
    • University General Hospital of Larissa
  • Chaïdári, Greece
    • University General Hospital "Attikon"
  • Kifisiá, Greece
    • General Oncology Hospital of Kifissia " Agioi Anargyroi"
  • Larissa, Greece
    • General Hospital of Patra "Agios Andreas"
  • Patra, Greece
    • University General Hospital "Attikon"
• Hong Kong
  • Hong Kong, Hong Kong
    • Queen Mary Hospital
  • Hong Kong, Hong Kong
    • Princess Margaret Hospital
  • Hong Kong, Hong Kong
    • Hong Kong United Oncology Centre
  • Hong Kong, Hong Kong
    • Hong Kong Integrated Oncology Centre
  • Hong Kong, Hong Kong
    • Humanity and Health Clinical Trial Centre
• Korea, Republic of
  • Busan, Korea, Republic of
    • Dong-a University hospital
  • Busan, Korea, Republic of
    • Kosin University Gospel Hospital
  • Cheongju, Korea, Republic of
    • Chungbuk National University Hospital
  • Daegu, Korea, Republic of
    • Keimyung University Dongsan Hospital
  • Gyeonggi-do, Korea, Republic of
    • The Catholic University of Korea Eunpyeong St Mary's Hospital
  • Gyeongsang, Korea, Republic of
    • Gyeongsang National University Hospital
  • Incheon, Korea, Republic of
    • Inha University Hospital
  • Incheon, Korea, Republic of
    • The Catholic University of Korea Incheon St. Mary's Hospital
  • Incheon, Korea, Republic of
    • Gachon University Gil Medical Centre
  • Jeonju, Korea, Republic of
    • Jeonbuk National University Hospital
  • Seongnam, Korea, Republic of
    • Cha Bundang Medical Centre Cha University
  • Seoul, Korea, Republic of, 6351
    • Samsung Medical Center
  • Seoul, Korea, Republic of
    • Gangnam Severance Hospital
  • Seoul, Korea, Republic of
    • Korea University Anam Hospital
  • Seoul, Korea, Republic of
    • Kangbuk Samsung Hospital
  • Seoul, Korea, Republic of
    • Asan Medical Centre
  • Seoul, Korea, Republic of
    • The Catholic University of Korea Seoul St Mary's Hospital
  • Suwon-Si, Korea, Republic of
    • Ajou University Hospital
  • Suwon-Si, Korea, Republic of
    • The Catholic University Of Korea St. Vincent Hospital
  • Yangsan, Korea, Republic of
    • Pusan National University Yangsan Hospital
• Malaysia
  • Cheras, Malaysia
    • Universiti Kebangsaan Malaysia
  • Jalan Baharu, Malaysia
    • Institut Kanser Negara
  • Johor Bahru, Malaysia
    • Hospital Sultan Ismail
  • Kuala Lumpur, Malaysia
    • University Malaya Medical Centre
  • Kuala Lumpur, Malaysia
    • Pantai Hospital Kuala Lumpur
  • Kuala Lumpur, Malaysia
    • Hospital Kuala Lumpar
  • Kuantan, Malaysia
    • Hospital Tengku Ampuan Afzan
  • Kuching, Malaysia
    • Hospital Umum Sarawak
  • Pulau Pinang, Malaysia
    • Hospital Pulau Pinang
  • Tanjung Bungah, Malaysia
    • Mount Miriam Cancer Hospital
• Mexico
  • Benito Juarez, Mexico
    • Health Pharma Professional Research
  • Guadalajara, Mexico
    • Antiguo Hospital Civil de Guadalajara Fray Antonio Alcalde
  • Guadalajara, Mexico
    • Hospital Civil Fray Antonio Alcalde
  • Mexico City, Mexico
    • Health Pharma Professional Research S.A. de C.V.
  • Monterrey, Mexico
    • Universidad Autonoma de Nuevo Leon, Hospital Universitario Dr. Jose Eleuterio Gonzalez
  • Oaxaca, Mexico
    • Oaxaca Site Management Organization S.C.
  • San Luis Potosi, Mexico
    • Oncológico Potosino
• Peru
  • Arequipa, Peru
    • Hospital Goyeneche
  • San Borja, Peru
    • Oncosalud
  • San Isidro, Peru
    • Clinica Ricardo Palma
• Philippines
  • Baguio City, Philippines
    • Baguio General Hospital Medical Centre
  • Cebu, Philippines
    • Chong Hua Hospital
  • Cebu City, Philippines
    • Chung Shan Medical University Hospital
  • Davao City, Philippines
    • Metro Davao Medical and Research Centre
  • Makati City, Philippines
    • Makati Medical Centre
  • Manila, Philippines
    • Philippine General Hospital
  • Manila, Philippines
    • University of Santo Tomas Hospital
  • Quezon City, Philippines
    • St. Luke Medical Centre Quezon City
• Serbia
  • Belgrade, Serbia
    • Clinical Center of Serbia
  • Belgrade, Serbia
    • Clinical Center "Bezanijska kosa"
  • Belgrade, Serbia
    • Oncomed System
  • Kragujevac, Serbia
    • Clinical Center Kragujevac
  • Nis, Serbia
    • Clinical Center Nis
  • Sremska Kamenica, Serbia
    • Institute For Pulmonary Diseases of Vojvodina
  • Uzice, Serbia
    • General Hospital Uzice
• Slovakia
  • Banka, Slovakia
    • Slovak Research Center- team member, Ambulancia klinickej onkologie
  • Kosice, Slovakia
    • Vychodoslovensky onkologicky ustav, a.s.
  • Michalovce, Slovakia
    • Nemocnica s poliklinikou Stefana Kukuru Michalovce, a.s.
  • Partizanske, Slovakia
    • Nemocnica na okraji mesta, n.o.
  • Trnava, Slovakia
    • Fakultna nemocnica Trnava
• South Africa
  • Cape Town, South Africa
    • Tygerberg Hospital
  • George, South Africa
    • Exellentis Clinical Trial Consultants
  • Johannesburg, South Africa
    • The Medical Oncology Centre of Rosebank
  • Johannesburg, South Africa
    • Cancercare PE
  • Johannesburg, South Africa
    • West Rand Oncology Centre
  • Johannesburg, South Africa
    • Wits Clinical Research CMJAH Clinical Trial Site
  • Port Elizabeth, South Africa
    • Port Elizabeth Oncology Centre-Cancercare
  • Pretoria, South Africa
    • Wilgers Oncology Centre
  • Pretoria, South Africa
    • Little Company of Mary Oncology Centre - Mary Potter Cancer Centre
  • Pretoria, South Africa
    • University of Pretoria Medical Oncology
• Taiwan
  • Kaohsiung City, Taiwan
    • Kaohsiung Medical University Chung-Ho Memorial Hospital
  • Kaohsiung City, Taiwan
    • Chang Gung Medical Foundation Kaohsiung
  • Taichung, Taiwan
    • Chung Shan Medical University Hospital
  • Taichung City, Taiwan
    • China Medical University Hospital
  • Taichung City, Taiwan
    • Chung Shan Medical University Hospital
  • Taichung City, Taiwan
    • Taichung Veterans General Hospital
  • Taipei, Taiwan
    • Taipei Medical University Hospital
• Thailand
  • Bangkok, Thailand
    • Siriraj Hospital
  • Bangkok, Thailand
    • Rajavithi Hospital
  • Bangkok, Thailand
    • King Chulalongkorn Memorial Hospital
  • Bangkok, Thailand
    • Phramongkutklao Hospital
  • Bangkok, Thailand
    • Police General Hospital
  • Bangkok, Thailand
    • Vajira Hospital
  • Chanthaburi, Thailand
    • Prapokklao Hospital
  • Chiang Mai, Thailand
    • Nakornping Hospital
  • Chiang Mai, Thailand
    • Maharaj Nakorn Chiang Mai Hospital
  • Khon Kaen, Thailand
    • Srinagarind Hospital
  • Lampang, Thailand
    • Lampang Hospital
  • Nakhon Ratchasima, Thailand
    • Maharat Nakhon Ratchasima Hospital
  • Ongkharak, Thailand
    • HRH Princess Maha Chakri Sirindhorn Medical Centre
  • Phitsanulok, Thailand
    • Naresuan University Hospital
  • Phitsanulok, Thailand
    • Buddhachinaraj Phitsanulok Hospital
  • Saraburi, Thailand
    • Saraburi Hospital
  • Songkhla, Thailand
    • Songkhlanagarind Hospital
  • Ubon Ratchathani, Thailand
    • Sunpasitthiprasing Hospital
  • Udon Thani, Thailand
    • Udon Thani Hospital
• Turkey
  • Adana, Turkey
    • Cukurova University Medical Faculty
  • Adana, Turkey
    • Baskent University Adana Application and Research Center
  • Adana, Turkey
    • Adana City Hospital
  • Ankara, Turkey
    • Ankara City Hospital
  • Ankara, Turkey
    • Gazi University Medical Faculty
  • Ankara, Turkey
    • Hacettepe University Medical Faculty
  • Ankara, Turkey
    • Memorial Ankara Hospital
  • Diyarbakir, Turkey
    • Dicle University, Medical Faculty
  • Edirne, Turkey
    • Trakya University Medical Faculty
  • Istanbul, Turkey
    • Istanbul University Cerrahpasa - Cerrahpasa Medical Faculty
  • Istanbul, Turkey
    • Goztepe Prof. Dr. Suleyman Yalcin City Hospital
  • Istanbul, Turkey
    • Acibadem Atakent Hospital
  • Istanbul, Turkey
    • Medipol University Medical Faculty
  • Kocaeli, Turkey
    • Kocaeli Universitesi Tip Fakultesi
  • Malatya, Turkey
    • Inonu Uni. Med. Fac.
  • Mersin, Turkey
    • Mersin University Medical Faculty
• United States
  • California
    • Thousand Oaks, California, United States, 91360
      • Millennium Reasearch & Clinical Development
  • Georgia
    • Columbus, Georgia, United States, 31904
      • Centricity Research
  • Illinois
    • Hinsdale, Illinois, United States, 60521
      • Affinity Health Hope & Healing Cancer Services
  • Ohio
    • Canton, Ohio, United States, 44718
      • Gabrail Cancer Center
    • Cleveland, Ohio, United States, 44106
      • VA Notheast Ohio Healthcare System
    • Columbus, Ohio, United States, 31904
      • Centricity Research Columbus Cancer Center
  • Texas
    • Houston, Texas, United States, 77090
      • Millennium Research
    • Kingwood, Texas, United States, 77339
      • Lumi Research
  • Virginia
    • Roanoke, Virginia, United States, 24014
      • Blue Ridge Cancer Center
• Vietnam
  • Cần Thơ, Vietnam
    • Cần Thơ Oncology Hospital
  • Ho Chi Minh City, Vietnam
    • Pham Ngo Thach Hospital
  • Huế, Vietnam
    • Huế Central Hospital
  • Hà Nội, Vietnam
    • 103 Military Hospital
  • Hà Nội, Vietnam
    • 175 Military Hospital
  • Hà Nội, Vietnam
    • Bach Mai Hospital
  • Hà Nội, Vietnam
    • Cho Ray Hospital
  • Hà Nội, Vietnam
    • Hanoi Oncology Hospital
  • Hà Nội, Vietnam
    • HCM Oncology Hospital
  • Hà Nội, Vietnam
    • Ho Chi Minh City University Medical Centre
  • Hà Nội, Vietnam
    • National Lung Hospital
  • Hà Nội, Vietnam
    • Nghe An Oncology Hospital
  • Hà Nội, Vietnam
    • People's Hospital 115
  • Hà Nội, Vietnam
    • Vietnam National Cancer Hospital

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Histologically confirmed, treatment naïve, locally advanced or metastatic (stage IIIB IV per AJCC version 8), squamous or non-squamous NSCLC with documented high PD L1 expression (TC ≥ 50%) as determined by the VENTANA SP263 IHC assay, as assessed by central laboratories).
• 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

• If a participant has brain or meningeal metastases, the participant must meet the following criteria:

  1. Have no evidence of progression by neurologic symptoms or signs for at least 4 weeks prior to the first dose.
  2. Participants with previously treated brain metastases may participate provided they have stable central nervous system (CNS) disease for at least 4 weeks prior to enrollment. Stable CNS disease is defined as resolution of all neurologic symptoms to baseline, having no evidence of new or enlarging brain metastases, and not requiring use of corticosteroids for CNS disease for at least 14 days prior to the start of study treatment. Participants who have had brain metastases resected or have received whole brain radiotherapy ending at least 4 weeks (or stereotactic radiotherapy ending at least 2 weeks) prior to initiation of study treatment are permitted.
  3. Carcinomatous meningitis is excluded regardless of clinical stability.

Exclusion Criteria:

• Presence of any tumor genomic aberration or driver mutation for which a targeted therapy is approved by local health authority and available
• Use of any live vaccines against infectious diseases within 28 days of first dose
• 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
• Prior treatment with any anti-PD-1, anti-PD-L1 or any other antibody targeting an immune checkpoint.

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

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Arm A - Study Part 1 (Platinum-based Chemotherapy); Participants will receive carboplatin, pemetrexed, and paclitaxel by intravenous (IV) infusion.	Drug: Carboplatin; Participants receive carboplatin, pemetrexed, and paclitaxel at a target area under the curve.; Drug: Pemetrexed; Participants receive carboplatin, pemetrexed, and paclitaxel at a target area under the curve.; Drug: Paclitaxel; Participants receive carboplatin, pemetrexed, and paclitaxel at a target area under the curve.
Experimental: Arm B - Study Part 1 (Zimberelimab Monotherapy); Participants will receive zimberelimab monotherapy by IV infusion.	Drug: Zimberelimab; Zimberelimab is a fully human anti-PD-1 monoclonal antibody; Other Names: AB122
Active Comparator: Arm C - Study Part 1 (Domvanalimab + Zimberelimab Combination Therapy); Participants will receive zimberelimab in combination with AB154 by IV infusion.	Drug: Zimberelimab; Zimberelimab is a fully human anti-PD-1 monoclonal antibody; Other Names: AB122; Drug: Domvanalimab; Domvanalimab is a humanized monoclonal antibody targeting human TIGIT; Other Names: AB154
Experimental: Arm D - Study Part 2 (Domvanalimab + Zimberelimab Combination Therapy); Participants will receive domvanalimab in combination with zimberelimab by IV infusion.	Drug: Zimberelimab; Zimberelimab is a fully human anti-PD-1 monoclonal antibody; Other Names: AB122; Drug: Domvanalimab; Domvanalimab is a humanized monoclonal antibody targeting human TIGIT; Other Names: AB154
Experimental: Arm E - Study Part 2 (Pembrolizumab); Participants will receive pembrolizumab by IV infusion.	Drug: Pembrolizumab; Pembrolizumab is a humanized Immunoglobulin G4 monoclonal antibody targeting the PD-1 receptor

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS)	Arm D vs. Arm E	From randomization until death from any cause (up to approximately 7 years)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free Survival (PFS)	Arm D vs. Arm E - PFS as assessed by RECIST v1.1 by blinded independent central review	From randomization until death from any cause (up to approximately 7 years)
Confirmed Overall Response Rate (ORR)	Arm D vs. Arm E - ORR as assessed by RECIST v1.1 by blinded independent central review	From randomization until death from any cause (up to approximately 7 years)
Number of Participants With treatment-emergent adverse events	Arm D vs. Arm E	From randomization until death from any cause (up to approximately 7 years)
Time to first symptom deterioration in Non-Small Cell Lung Cancer Symptom Assessment Questionnaire (NSCLC-SAQ) total score	Arm D vs. Arm E	From randomization until death from any cause (up to approximately 7 years)

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): February 8, 2021
• Primary Completion (Estimated): August 31, 2024
• Study Completion (Estimated): July 1, 2027

Study Registration Dates

• First Submitted: January 29, 2021
• First Submitted That Met QC Criteria: January 29, 2021
• First Posted (Actual): February 3, 2021

Study Record Updates

• Last Update Posted (Actual): March 15, 2024
• Last Update Submitted That Met QC Criteria: March 13, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Lung Cancer; NSCLC; Non Small Cell Lung Cancer
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Molecular Mechanisms of Pharmacological Action; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Folic Acid Antagonists; Carboplatin; Paclitaxel; Pembrolizumab; Pemetrexed
• Other Study ID Numbers: ARC-10; 2020-003562-39 (EudraCT Number); PHRR210222-003371 (Other Identifier: Philippine Health Research Registry)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Arcus will provide access to individual de-identified participant data and related study documents (e.g., protocol, Statistical Analysis Plan [SAP], Clinical Study Report [CSR]) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions.

For more information, please visit our website.

• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

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