NCT04262856

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.

Trial Health

93
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
151

participants targeted

Target at P75+ for phase_2

Timeline
Completed

Started May 2020

Longer than P75 for phase_2

Geographic Reach
7 countries

44 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

January 23, 2020

Completed
18 days until next milestone

First Posted

Study publicly available on registry

February 10, 2020

Completed
4 months until next milestone

Study Start

First participant enrolled

May 28, 2020

Completed
5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

June 5, 2025

Completed
1 month until next milestone

Study Completion

Last participant's last visit for all outcomes

July 9, 2025

Completed
Last Updated

August 26, 2025

Status Verified

August 1, 2024

Enrollment Period

5 years

First QC Date

January 23, 2020

Last Update Submit

August 25, 2025

Conditions

Keywords

Non Small Cell Lung CancerLung CancerNSCLC

Outcome Measures

Primary Outcomes (2)

  • Objective response rate (ORR)

    ORR as assessed by RECIST v1.1

    From randomization until the first documentation of disease progression or death from any cause, whichever occurs first (up to approximately 3-5 years)

  • Progression-free survival (PFS)

    PFS as assessed by RECIST v1.1

    From randomization until the first documentation of disease progression or death from any cause, whichever occurs first (up to approximately 3-5 years)

Secondary Outcomes (9)

  • 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)

  • 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)

  • Overall Survival (OS)

    From randomization to death from any cause (up to approximately 5 years)

  • Number of Participants with Treatment Emergent Adverse Events (TEAEs)

    From Screening until up to 90-100 days after the last dose (approximately 5 years)

  • 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)

  • +4 more secondary outcomes

Study Arms (3)

Arm 1 (zimberelimab monotherapy)

EXPERIMENTAL

Participants will receive zimberelimab as an intravenous (IV) infusion.

Drug: Zimberelimab

Arm 2 (domvanalimab and zimberelimab combination therapy)

EXPERIMENTAL

Participants will receive domvanalimab IV in combination with zimberelimab IV infusion.

Drug: DomvanalimabDrug: Zimberelimab

Arm 3 (domvanalimab, etrumadenant, and zimberelimab combination therapy)

EXPERIMENTAL

Participants will receive oral etrumadenant in combination with domvanalimab IV and zimberelimab IV infusion

Drug: DomvanalimabDrug: EtrumadenantDrug: Zimberelimab

Interventions

Domvanalimab is a humanized monoclonal antibody targeting human TIGIT

Also known as: AB154
Arm 2 (domvanalimab and zimberelimab combination therapy)Arm 3 (domvanalimab, etrumadenant, and zimberelimab combination therapy)

Etrumadenant is an A2aR and A2bR antagonist

Also known as: AB928
Arm 3 (domvanalimab, etrumadenant, and zimberelimab combination therapy)

Zimberelimab is a fully human anti-PD-1 monoclonal antibody

Also known as: AB122
Arm 1 (zimberelimab monotherapy)Arm 2 (domvanalimab and zimberelimab combination therapy)Arm 3 (domvanalimab, etrumadenant, and zimberelimab combination therapy)

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (44)

University of Alabama at Birmingham

Birmingham, Alabama, 35294, United States

Location

Innovative Clinical Research Institute (ICRI)

Whittier, California, 90603, United States

Location

Florida Cancer Specialists

Englewood, Florida, 34223, United States

Location

Florida Cancer Specialists

Gainesville, Florida, 32605, United States

Location

Florida Cancer Specialists - Panhandle

Tallahassee, Florida, 32308, United States

Location

Florida Cancer Specialists - East

West Palm Beach, Florida, 33401, United States

Location

Baptist Health Lexington

Lexington, Kentucky, 40503, United States

Location

Norton Cancer Institute

Louisville, Kentucky, 40202, United States

Location

Ochsner Clinic Foundation

New Orleans, Louisiana, 70121, United States

Location

The Valley Hospital - Valley Health System - The Robert and Audrey Luckow Pavilion

Ridgewood, New Jersey, 07450, United States

Location

Clinical Research Alliance

Lake Success, New York, 11042, United States

Location

Northwell Health Cancer Institute

Lake Success, New York, 11042, United States

Location

Wake Forest Baptist Health

Winston-Salem, North Carolina, 27157, United States

Location

Allegheny General Hospital (AGH)-Alleghney Singer Research Institute

Pittsburgh, Pennsylvania, 15224, United States

Location

Sarah Cannon Research Institute

Nashville, Tennessee, 37203, United States

Location

The Center For Cancer And Blood Disorders (Texas Cancer Care)

Fort Worth, Texas, 76104, United States

Location

Millennium Oncology

Houston, Texas, 77339, United States

Location

Oncology and Hematology Associates of Southwest Virginia, Inc., DBA Blue Ridge Cancer Care

Blacksburg, Virginia, 24060, United States

Location

Virginia Cancer Specialists

Fairfax, Virginia, 22031, United States

Location

Border Medical Oncology

Albury, Australia

Location

Coffs Harbour Health Campus

Coffs Harbour, Australia

Location

Adelaide Cancer Centre

Elizabeth Vale, Australia

Location

Shoalhaven Cancer Care Centre

Nowra, Australia

Location

McGill University Health Centre (MUHC) - The Montreal Children's Hospital (MCH)

Montreal, Canada

Location

Hong Kong United Oncology Centre

Hong Kong, Hong Kong

Location

Queen Elizabeth Hospital (Hong Kong)

Hong Kong, Hong Kong

Location

Curie Oncology

Singapore, Singapore

Location

Kosin University Gospel Hospital

Busan, South Korea

Location

Chungbuk National University Hospital (CBNUH)

Cheongju-si, South Korea

Location

Chonnam University Hospital

Hwasun, South Korea

Location

Gachon University Gil Medical Center

Incheon, South Korea

Location

Chonbuk National University Hospital

Jeonju, South Korea

Location

Seoul National University Bundang Hospital

Seongnam-si, South Korea

Location

Asan Medical Center

Seoul, South Korea

Location

Kangbuk Samsung Hospital

Seoul, South Korea

Location

Korea University Anam Hospital

Seoul, South Korea

Location

St Vincent Hospital of the Catholic University of Korea

Suwon, South Korea

Location

Catholic University of Korea, Uijeongbu St. Mary's Hospital

Uijeongbu-si, South Korea

Location

Taipei Medical University - Shuang Ho Hospital

New Taipei City, Taiwan

Location

Chi Mei Hospital

Tainan, Taiwan

Location

National Cheng Kung University Hospital

Tainan, Taiwan

Location

National Taiwan University Hospital

Taipei, Taiwan

Location

Taipei Medical University Hospital

Taipei, Taiwan

Location

Chang Gung Memorial Hospital at Linkou

Taoyuan District, Taiwan

Location

Related Links

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell LungLung Neoplasms

Interventions

zimberelimab

Condition Hierarchy (Ancestors)

Carcinoma, BronchogenicBronchial NeoplasmsRespiratory Tract NeoplasmsThoracic NeoplasmsNeoplasms by SiteNeoplasmsLung DiseasesRespiratory Tract Diseases

Study Officials

  • Medical Director

    Arcus Biosciences, Inc.

    STUDY DIRECTOR

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

January 23, 2020

First Posted

February 10, 2020

Study Start

May 28, 2020

Primary Completion

June 5, 2025

Study Completion

July 9, 2025

Last Updated

August 26, 2025

Record last verified: 2024-08

Data Sharing

IPD Sharing
Will share

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.

Shared Documents
STUDY PROTOCOL, SAP, CSR
More information

Locations