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Safety and Efficacy of Zimberelimab (AB122) in Combination With Domvanalimab (AB154) and Etrumadenant (AB928) in Patients With Previously Treated Non-Small Cell Lung Cancer

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ClinicalTrials.gov Identifier: NCT04791839
Recruitment Status : Recruiting
First Posted : March 10, 2021
Last Update Posted : September 17, 2021
Sponsor:
Collaborator:
Arcus Biosciences, Inc.
Information provided by (Responsible Party):
Washington University School of Medicine

Tracking Information
First Submitted Date  ICMJE March 5, 2021
First Posted Date  ICMJE March 10, 2021
Last Update Posted Date September 17, 2021
Actual Study Start Date  ICMJE August 4, 2021
Estimated Primary Completion Date November 30, 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 5, 2021)
Objective response rate (ORR) [ Time Frame: Through completion of treatment (estimated to be 9 months) ]
  • Defined as the proportion of patients achieving CR or PR
  • Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. Disappearance of all non-target lesions and normalization of tumor marker level.
Partial Response (PR): At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: March 5, 2021)
  • Number of study treatment related adverse events [ Time Frame: From start of treatment through 100 days after last treatment (estimated to be 9 months and 100 days) ]
    - Adverse events will be assessed using CTCAE v5.0 criteria
  • Number of discontinuations due to treatment-related adverse events [ Time Frame: From start of treatment through 100 days after last treatment (estimated to be 9 months and 100 days) ]
    - Adverse events will be assessed using CTCAE v5.0 criteria
  • Progression-free survival (PFS) [ Time Frame: Through completion of follow-up (estimated to be 5 years) ]
    • Progression-free survival (PFS), defined as the duration of time from the start date of study treatment to the date of earliest progression or death, whichever occurs first. Patients who neither progress nor die by the data cutoff date will be censored at the last follow up date.
    • Progressive Disease (PD): At least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions.
  • Duration of response (DoR) [ Time Frame: Through completion of treatment (estimated to be 9 months) ]
    • Duration of response (DoR), defined as the time from the confirmation of a CR, PR, or SD (whichever is first recorded), until the first date that recurrent or progressive disease is objectively documented.
    • Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. Disappearance of all non-target lesions and normalization of tumor marker level.
    • Partial Response (PR): At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.
    • Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.
  • Disease control rate (DCR) [ Time Frame: Through completion of treatment (estimated to be 9 months) ]
    • Disease control rate (DCR), defined as the proportion of patients achieving CR, PR, or SD measured according to RECIST 1.1.
    • Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. Disappearance of all non-target lesions and normalization of tumor marker level.
    • Partial Response (PR): At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.
    • Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.
  • Overall survival (OS) [ Time Frame: Through completion of follow-up (estimated to be 5 years) ]
    - Overall survival (OS), defined as the duration of time from the start date of study treatment to death from any cause. Patients who are alive by the data cutoff date will be censored at the last follow up date.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Safety and Efficacy of Zimberelimab (AB122) in Combination With Domvanalimab (AB154) and Etrumadenant (AB928) in Patients With Previously Treated Non-Small Cell Lung Cancer
Official Title  ICMJE A Pilot Study to Evaluate the Safety and Efficacy of Zimberelimab (AB122) in Combination With Domvanalimab (AB154) and Etrumadenant (AB928) in Patients With Previously Treated Non-Small Cell Lung Cancer
Brief Summary Since anti-PD1, anti-TIGIT, and A2R antagonists have complementary mechanisms of action, and the latter two have shown synergism in combination with antibodies against PD-1, othis study aims to evaluate the efficacy and tolerability of the triplet combination of zimberelimab, domvanalimab, and etrumadenant in patients with non-small cell lung cancer previously treated with immune checkpoint blockade therapy.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Non Small Cell Lung Cancer
  • Non-small Cell Carcinoma
  • Non-small Cell Lung Cancer
Intervention  ICMJE
  • Drug: Zimberelimab
    Zimberelimab will be supplied by Arcus Biosciences.
  • Drug: Domvanalimab
    Domvanalimab will be supplied by Arcus Biosciences.
  • Drug: Etrumadenant
    Etrumadenant will be supplied by Arcus Biosciences.
Study Arms  ICMJE
  • Experimental: Cohort A: Zimberelimab + Domvanalimab + Etrumadenant
    • Patients will be treated on 21-day cycles with 360 mg zimberelimab intravenously on Day 1, 15 mg/kg domvanalimab intravenously on Day 1, and 150 mg etrumadenant orally daily on Days 1 to 21.
    • Cohort A participants are those that have PD-L1 1-49%
    Interventions:
    • Drug: Zimberelimab
    • Drug: Domvanalimab
    • Drug: Etrumadenant
  • Experimental: Cohort B: Zimberelimab + Domvanalimab + Etrumadenant
    • Patients will be treated on 21-day cycles with 360 mg zimberelimab intravenously on Day 1, 15 mg/kg domvanalimab intravenously on Day 1, and 150 mg etrumadenant orally daily on Days 1 to 21.
    • Cohort B participants are those that have PD-L1 ≥ 50%.
    Interventions:
    • Drug: Zimberelimab
    • Drug: Domvanalimab
    • Drug: Etrumadenant
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: March 5, 2021)
30
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE February 28, 2028
Estimated Primary Completion Date November 30, 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Histologically confirmed metastatic squamous or non-squamous non-small cell lung cancer.
  • Previously treated with at least one line of therapy including an immune checkpoint blocker and no more than 2 prior lines in the metastatic setting.
  • Documented PD-L1 expression of at least 1% by PharmDx 22C3 by a US FDA-approved PD-L1 assay from archival biopsy or fresh tumor tissue.
  • At least one measurable lesion per RECIST 1.1 criteria.
  • At least 18 years of age.
  • ECOG performance status ≤ 1.
  • Normal bone marrow and organ function as defined below:

    • Absolute neutrophil count ≥ 1,500/µL
    • Platelets ≥ 100,000/µL
    • Hemoglobin ≥ 9.0 g/dL
    • Total bilirubin ≤ 2.0 x IULN (except participants with Gilbert's syndrome who must have total bilirubin < 3.0 mg/dL)
    • AST(SGOT)/ALT(SGPT) ≤ 2.5 x IULN without hepatic metastasis and ≤ 5.0 x IULN with hepatic metastasis
  • Patients with brain or meningeal metastases are eligible provided they meet the following criteria:

    • No evidence of progression by neurologic symptoms or signs for at least 4 weeks prior to first dose of study treatment
    • Metastatic brain lesions that do not require immediate intervention
    • No use of corticosteroids with dose above 10 mg prednisone (or equivalent)
  • The effects of the study drugs on the developing human fetus are unknown. For this reason, women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control, abstinence) prior to study entry, for the duration of study participation, and for 100 days after completion of study treatment. Should a woman become pregnant or suspect she is pregnant while participating in this study, she must inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of the study, and 100 days after completion of study treatment.
  • Ability to understand and willingness to sign an IRB approved written informed consent document (or that of legally authorized representative, if applicable).

Exclusion Criteria:

  • A history of other malignancy with the exception of malignancies for which all treatment was completed at least 2 years before registration and the patient has no evidence of disease.
  • Patients with EGFR mutation, ALK rearrangement, ROS1 fusion or RET fusion are excluded from the study.
  • Currently receiving any other investigational agents or having received any investigational agents within 28 days or 5 half-lives of first dose of trial treatment.
  • A history of allergic reactions attributed to compounds of similar chemical or biologic composition to zimberelimab, domvanalimab, etrumadenant, or other agents used in the study. Known hypersensitivity to recombinant proteins or any excipient contained in the trial formulations.
  • Use of any live vaccines against infectious diseases within 28 days of first dose of trial treatment.
  • Any gastrointestinal condition that would preclude the use of oral medications (e.g. difficulty swallowing, nausea, vomiting, or malabsorption).
  • History of trauma or major surgery within 28 days prior to the first dose of study treatment.
  • Underlying medical conditions that in the investigator's opinion will make the administration of study treatment hazardous, including but not limited to:

    • Interstitial lung disease, including history of interstitial lung disease or noninfectious pneumonitis
    • Active viral, bacterial or fungal infection requiring parenteral treatment within 14 days of the initiation of study treatment
    • Clinically significant cardiovascular disease
    • A condition that may obscure the interpretation of toxicity determination or AEs
    • History of prior solid organ transplantation
  • Concurrent medical condition requiring the use of supra-physiologic doses of corticosteroids (> 10 mg/day of oral prednisone or equivalent) or immunosuppressive medications (with the exception of absorbable topical corticosteroids).
  • Positive test results for hepatitis B surface antigen, hepatitis C virus antibody, hepatitis C qualitative RNA, or human immunodeficiency virus-1 antibody at screening.
  • Known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
  • Any active autoimmune disease or documented history of autoimmune disease or syndrome that required systemic treatment in the past 2 years (i.e. with use of disease-modifying agents, corticosteroids, or immunosuppressive drugs) except for vitiligo or resolved childhood asthma/atopy.

    • Replacement therapy (e.g. thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment
    • Participants with asthma who require intermittent use of bronchodilators, inhaled corticosteroids, or local corticosteroid injections will not be excluded from this study. Participants on chronic systemic corticosteroids will be excluded.
  • Pregnant and/or breastfeeding. Women of childbearing potential must have a negative pregnancy test within 14 days of study entry.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Daniel Morgensztern, M.D. 314-362-5817 danielmorgensztern@wustl.edu
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04791839
Other Study ID Numbers  ICMJE 202104122
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Washington University School of Medicine
Study Sponsor  ICMJE Washington University School of Medicine
Collaborators  ICMJE Arcus Biosciences, Inc.
Investigators  ICMJE
Principal Investigator: Daniel Morgensztern, M.D. Washington University School of Medicine
PRS Account Washington University School of Medicine
Verification Date September 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP