Study to Evaluate Monotherapy and Combination Immunotherapies in Participants With PD-L1 Positive Non-small Cell Lung Cancer (ARC-7)

Arcus Biosciences

Status and phase: Active, not recruiting; Phase 2

Conditions: Squamous Non Small Cell Lung Cancer; Nonsquamous Non Small Cell Lung Cancer; Lung Cancer; Non Small Cell Lung Cancer

Treatments: Drug: Etrumadenant; Drug: Zimberelimab; Drug: Domvanalimab

Study type: Interventional

Funder types: Industry

Identifiers

NCT04262856

ARC-7 (AB154CSP0002)

Details and patient eligibility

About

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.

Full description

This is an open-label phase 2 study in participants with non-small cell lung cancer which will assess the safety, efficacy and tolerability of zimberelimab as monotherapy and in combination with other immunotherapeutics across multiple treatment arms.

Approximately 150 participants will be randomized to 1 of 3 treatment arms: 1) zimberelimab, 2) zimberelimab + domvanalimab (anti-TIGIT antibody), 3) zimberelimab + domvanalimab + etrumadenant (dual adenosine receptor antagonist). Participants that progress on the zimberelimab monotherapy arm may cross-over to receive the third arm combination of zimberelimab + domvanalimab + etrumadenant.

The primary objective of this clinical study is to evaluate the efficacy of each combination therapy by assessing: 1) objective response rate (ORR) of participants with measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST v1.1) and 2) progression free survival (PFS).

Enrollment: 151 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Male or female participants; age ≥ 18 years
• Histologically confirmed, treatment naïve, 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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151 participants in 3 patient groups

Arm 1 (zimberelimab monotherapy)

Experimental group

Description:

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

Treatment:

Drug: Zimberelimab

Arm 2 (domvanalimab and zimberelimab combination therapy)

Experimental group

Description:

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

Treatment:

Drug: Domvanalimab

Drug: Zimberelimab

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

Experimental group

Description:

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

Treatment:

Drug: Domvanalimab

Drug: Etrumadenant

Drug: Zimberelimab