1419TiP - ARC-7: A phase II study to evaluate the safety and efficacy of zimberelimab alone, AB154 in combination with zimberelimab, and AB154 in combination with zimberelimab and AB928 in front-line, PD-L1 expressing, non-small cell lung cancer (NSCLC)

Background

In patients with NSCLC whose tumors express high levels of PD-L1, anti-PD-(L)1 checkpoint inhibitors have shown benefit in response and survival compared to platinum doublets. However, less than half of patients respond to monotherapy; combination therapies may improve response and survival. T cell Immunoglobulin and ITIM domain (TIGIT) is expressed on subsets of activated T cells and natural killer (NK) cells. Binding of TIGIT with CD155 suppresses the function of T cells and NK cells. AB154 is an anti-TIGIT humanized IgG1 monoclonal antibody with diminished FcgR binding. Adenosine activates the A_2a and A_2b receptors (R) on immune cells, contributing to an ineffective anti-tumor immune response. AB928 is the first clinical-stage small molecule dual antagonist of both A_2aR and A_2bR. This study will investigate whether addition of immune-active agents, anti-TIGIT and anti-adenosine, can augment the activity of a PD-1 antibody in PD-L1-expressing NSCLC.

Trial design

ARC-7 is a phase 2, multicenter, randomized, open-label study. Up to 150 patients (pts) with Stage IV, squamous or non-squamous non-small cell lung cancer, high PD-L1 expression, no EGFR or ALK genomic tumor aberrations, and an ECOG PS of 0 or 1 will be randomized in a 1:1:1 ratio to one of 3 arms: -Arm 1 (zimberelimab monotherapy): 360 mg by intravenous (IV) infusion every 3 weeks (Q3W) -Arm 2 (AB154 + zimberelimab): AB154 10 mg/kg by IV infusion every 2 weeks (Q2W) + zimberelimab 240 mg by IV infusion Q2W -Arm 3 (AB154 + zimberelimab + AB928): AB154 10 mg/kg by IV infusion Q2W + zimberelimab 240 mg by IV infusion Q2W + AB928 150 mg orally (PO) once daily (QD) Participants randomized to Arm 1 will have the option to cross over to Arm 3 at the time of confirmed PD (CPD). Participants who cross over will remain on treatment until their next CPD. No crossover will be allowed for pts in Arms 2 or 3. Co-primary endpoints are overall response rate and progression-free survival. ARC-7 is actively recruiting in the United States, Australia and countries in Asia; results will be shared in upcoming scientific conferences (NCT04262856).

Clinical trial identification

NCT04262856.

Editorial acknowledgement

Legal entity responsible for the study

Arcus Biosciences.

Funding

Arcus Biosciences.

Disclosure

A. Chaudhry: Speaker Bureau/Expert testimony, Research grant/Funding (institution): Bayer; Advisory/Consultancy: Exelixis; Advisory/Consultancy: Astellas; Research grant/Funding (institution), Shareholder/Stockholder/Stock options: Novartis; Research grant/Funding (institution): Arcus Biosciences; Research grant/Funding (institution): Merck; Research grant/Funding (institution): Ipsen; Research grant/Funding (institution): AbbVie; Research grant/Funding (institution): AstraZeneca; Research grant/Funding (institution): BMS; Research grant/Funding (institution): Alkermes; Research grant/Funding (institution): Eli Lilly; Research grant/Funding (institution): Pfizer; Research grant/Funding (institution): BeiGene; Research grant/Funding (institution): BerGenBio; Research grant/Funding (institution): Blueprint Medicines; Research grant/Funding (institution): Exelixis; Research grant/Funding (institution): Genentech; Research grant/Funding (institution): Gilead; Research grant/Funding (institution): Janssen; Research grant/Funding (institution): Millennium; Research grant/Funding (institution): Basilea; Research grant/Funding (institution): IunoCare; Research grant/Funding (institution): Amgen. M. Johnson: Honoraria (institution): Achilles Therapeutics; Honoraria (institution), Research grant/Funding (institution): AstraZeneca; Honoraria (institution), Research grant/Funding (institution): Atreca; Honoraria (institution), Research grant/Funding (institution): Boehringer Ingelheim; Honoraria (institution), Research grant/Funding (institution): Calithera Biosciences; Honoraria (institution), Research grant/Funding (institution): EMD Serono; Honoraria (institution), Research grant/Funding (institution): Genentech; Honoraria (institution), Research grant/Funding (institution): GSK; Honoraria (institution), Research grant/Funding (institution): Gritstone Oncology; Honoraria (institution), Research grant/Funding (institution): Guardant Health; Honoraria (institution), Research grant/Funding (institution): Incyte ; Honoraria (institution), Research grant/Funding (institution): Janssen; Honoraria (institution), Research grant/Funding (institution): Lilly; Honoraria (institution), Research grant/Funding (institution): Merck; Honoraria (institution), Research grant/Funding (institution): Mirati Therapeutics; Honoraria (institution), Research grant/Funding (institution): Novartis; Honoraria (institution), Research grant/Funding (institution): Pfizer; Honoraria (institution): Ribon Therapeutics; Honoraria (institution), Research grant/Funding (institution): Sanofi; Research grant/Funding (institution): Amgen; Research grant/Funding (institution): Regeneron; Research grant/Funding (institution): Apexigen; Research grant/Funding (institution): Shattuck Labs; Research grant/Funding (institution): Beigene; Research grant/Funding (institution): Stem Centrx; Research grant/Funding (institution): Array Biopharma; Research grant/Funding (institution): Checkpoint Therapeutics; Research grant/Funding (institution): Corvus; Research grant/Funding (institution): Cytmox; Research grant/Funding (institution): Arcus Biosciences. D. Colburn: Shareholder/Stockholder/Stock options, Full/Part-time employment: Arcus Biosciences; Shareholder/Stockholder/Stock options, Full/Part-time employment: Roche/Genentech. H. Gilbert: Shareholder/Stockholder/Stock options, Full/Part-time employment: Arcus Biosciences; Advisory/Consultancy, Full/Part-time employment: Bellicum; Shareholder/Stockholder/Stock options, Full/Part-time employment: Roche/Genentech; Shareholder/Stockholder/Stock options: Denali; Shareholder/Stockholder/Stock options: Celgene; Shareholder/Stockholder/Stock options: BMS. A. Garofalo: Shareholder/Stockholder/Stock options, Full/Part-time employment: Arcus Biosciences. M. Paoloni: Leadership role, Shareholder/Stockholder/Stock options, Full/Part-time employment: Arcus Biosciences; Advisory/Consultancy: Eli Lily; Advisory/Consultancy: Amgen; Advisory/Consultancy: Janssen. K. Krishnan: Leadership role, Shareholder/Stockholder/Stock options, Full/Part-time employment: Arcus Biosciences; Full/Part-time employment: Astex; Full/Part-time employment: Roche/Genentech; Full/Part-time employment: Five Prime.