Study to Evaluate Monotherapy and Combination Immunotherapies in Participants With PD-L1 Positive Non-small Cell Lung Cancer

Arcus Biosciences, Inc.151 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

151

Conditions

Non Small Cell Lung Cancer Nonsquamous Non Small Cell Lung Cancer Squamous Non Small Cell Lung Cancer Lung Cancer

Interventions

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * 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 Exclusion Criteria: * 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

Locations (44)

University of Alabama at Birmingham

Birmingham, Alabama, United States

Innovative Clinical Research Institute (ICRI)

Whittier, California, United States

Florida Cancer Specialists

Englewood, Florida, United States

Florida Cancer Specialists

Gainesville, Florida, United States

Florida Cancer Specialists - Panhandle

Tallahassee, Florida, United States

Outcomes

Primary Outcomes

Objective response rate (ORR)

ORR as assessed by RECIST v1.1

Time frame: 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

Time frame: 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

Duration of response (DoR)

DoR as assessed by RECIST v1.1

Time frame: 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)

DCR as assessed by RECIST v1.1

Overall Survival (OS)

OS as assessed at the time of PFS

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

Number of Participants with Treatment Emergent Adverse Events (TEAEs)

The number and percentage of participants that experience TEAE

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

Pharmacokinetics of zimberelimab

Serum concentration of zimberelimab as determined by validated assays

Time frame: 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)

Pharmacokinetics of domvanalimab

Serum concentration of domvanalimab as determined by validated assays

Time frame: 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)

Pharmacokinetics of etrumadenant

Serum concentration of etrumadenant as determined by validated assays

Time frame: 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)

Immunogenicity of zimberelimab

Percentage of participants who develop treatment-emergent anti-drug antibodies to zimberelimab

Time frame: Collected during all treatment cycles (each cycle is 21 or 28 days), up to 14 days post last dose, 30, and 100 days post last dose (in total, an average of 2 years).

Immunogenicity of domvanalimab

Percentage of participants who develop treatment-emergent anti-drug antibodies to domvanalimab

Time frame: Collected during all treatment cycles (each cycle is 21 or 28 days), up to 14 days post last dose, 30, and 100 days post last dose (in total, an average of 2 years).