Phase 3 Study Comparing Zimberelimab with Domvanalimab to Pembrolizumab in Advanced Non-Small Cell Lung Cancer

Recruitment & Eligibility

Status: Recruiting

Sex: All

Target Recruitment: 792

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: a. Have no evidence of progression by neurologic symptoms or signs for at least 4 weeks prior to the first dose, b) 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, c) 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 d) 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

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To evaluate the efficacy of zimberelimab and domvanalimab combination therapy compared to pembrolizumab in OS (Arm D vs Arm E);Secondary Objective: To evaluate the efficacy of zimberelimab and domvanalimab combination therapy compared to pembrolizumab in PFS and ORR (Arm D vs Arm E), To assess the safety of zimberelimab and domvanalimab combination therapy compared to pembrolizumab (Arm D vs Arm E), To compare the effect of zimberelimab and domvanalimab relative to pembrolizumab (Arm D vs Arm E) on health-related QOL using NSCLCSAQ;Primary end point(s): Overall survival (OS)

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s):PFS according to RECIST v1.1 by blinded independent central review, and confirmed ORR according to RECIST v1.1 as assessed by BICR.;Secondary end point(s):Presence of treatment-emergent adverse events, and Changes in vital signs measurements and clinical laboratory parameters;Secondary end point(s):Time to first symptom deterioration in NSCLC-SAQ total score

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