Clinical Trials /

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

NCT04262856

Description:

This Randomized Phase 2 Open-label Study will Evaluate the Safety and Efficacy of Zimberelimab (AB122) Monotherapy, AB154 in Combination with Zimberelimab, and AB154 in Combination with Zimberelimab and AB928 in Front-line, PD-L1 Positive, Locally Advanced or Metastatic Non-small Cell Lung Cancer.

Related Conditions:
  • Non-Small Cell Lung Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Study to Evaluate Monotherapy and Combination Immunotherapies in Participants With PD-L1 Positive Non-small Cell Lung Cancer
  • Official Title: A Phase 2 Study to Evaluate the Safety and Efficacy of AB122 Monotherapy, AB154 in Combination With AB122, and AB154 in Combination With AB122 and AB928 in Front-Line, Non-Small Cell Lung Cancer

Clinical Trial IDs

  • ORG STUDY ID: AB154CSP0002
  • NCT ID: NCT04262856

Conditions

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

Interventions

DrugSynonymsArms
ZimberelimabAB122Arm 1 (Zimberelimab Monotherapy)
AB154Arm 2 (AB154 and Zimberelimab Combination Therapy)
AB928Arm 3 (AB154, Zimberelimab, and AB928 Combination Therapy)

Purpose

This Randomized Phase 2 Open-label Study will Evaluate the Safety and Efficacy of Zimberelimab (AB122) Monotherapy, AB154 in Combination with Zimberelimab, and AB154 in Combination with Zimberelimab and AB928 in Front-line, PD-L1 Positive, Locally Advanced or Metastatic Non-small Cell Lung Cancer.

Detailed 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 + AB154 (anti-TIGIT antibody), 3) zimberelimab + AB154 + AB928 (dual
      adenosine receptor antagonist). Participants that progress on the zimberelimab monotherapy
      arm may cross-over to receive the third arm combination of zimberelimab + AB154 + AB928.

      The primary objective of this clinial 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).
    

Trial Arms

NameTypeDescriptionInterventions
Arm 1 (Zimberelimab Monotherapy)ExperimentalParticipants will receive zimberelimab monotherapy by IV infusion.
  • Zimberelimab
Arm 2 (AB154 and Zimberelimab Combination Therapy)ExperimentalParticipants will receive AB154 in combination with zimberelimab by IV infusion.
  • Zimberelimab
  • AB154
Arm 3 (AB154, Zimberelimab, and AB928 Combination Therapy)ExperimentalParticipants will receive oral AB928 in combination with zimberelimab and AB154 by IV infusion
  • Zimberelimab
  • AB154
  • AB928

Eligibility Criteria

        Inclusion Criteria:

          -  Male or female participants; age ≥ 18 years

          -  Histologically confirmed squamous or nonsquamous, PD-L1 positive, NSCLC that is
             locally advanced or metastatic without sensitizing epidermal growth factor receptor
             (EGFR) or anaplastic lymphoma kinase (ALK) mutation expression

          -  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

          -  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 or
             Hepatitis C qualitative RNA or human immunodeficiency virus-1 (HIV-1) antibody

          -  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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Objective response rate (ORR)
Time Frame:From randomization until death from any cause (up to approximately 3-5 years)
Safety Issue:
Description:ORR as assessed by RECIST v1.1

Secondary Outcome Measures

Measure:Duration of response (DoR)
Time Frame:From the date of first occurence 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)
Safety Issue:
Description:DoR as assessed by RECIST v1.1
Measure:Disease control rate (DCR)
Time Frame:From the date of first occurence of a documented objective response to first documentation of disease progression on death from any cause, whichever occurs first (up to approximately 3-5 years)
Safety Issue:
Description:DCR as assessed by RECIST v1.1
Measure:Adverse Events
Time Frame:From Screening until up to 100 days after the last dose (approximately 2 years)
Safety Issue:
Description:The number and percentage of participants that experience an adverse event (AE)
Measure:Pharmacodynamics of AB122
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).
Safety Issue:
Description:Plasma concentration of AB122
Measure:Pharmacodynamics of AB154
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).
Safety Issue:
Description:Plasma concentration of AB154
Measure:Pharmacodynamics of AB928
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).
Safety Issue:
Description:Plasma concentration of AB928
Measure:Immunogenicity of AB122
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).
Safety Issue:
Description:Percentage of participants who develop treatment-emergent anti-drug antibodies to AB122
Measure:Immunogenicity of AB154
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).
Safety Issue:
Description:Percentage of participants who develop treatment-emergent anti-drug antibodies to AB154

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Arcus Biosciences, Inc.

Trial Keywords

  • Non Small Cell Lung Cancer
  • Lung Cancer
  • NSCLC

Last Updated

February 7, 2020