Clinical Trials /

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

NCT04791839

Description:

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.

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

Not yet recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: 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: 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

Clinical Trial IDs

  • ORG STUDY ID: 202104122
  • NCT ID: NCT04791839

Conditions

  • Non Small Cell Lung Cancer
  • Non-small Cell Carcinoma
  • Non-small Cell Lung Cancer

Interventions

DrugSynonymsArms
ZimberelimabCohort A: Zimberelimab + Domvanalimab + Etrumadenant
DomvanalimabCohort A: Zimberelimab + Domvanalimab + Etrumadenant
EtrumadenantCohort A: Zimberelimab + Domvanalimab + Etrumadenant

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
Cohort A: Zimberelimab + Domvanalimab + EtrumadenantExperimentalPatients 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%
  • Zimberelimab
  • Domvanalimab
  • Etrumadenant
Cohort B: Zimberelimab + Domvanalimab + EtrumadenantExperimentalPatients 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%.
  • Zimberelimab
  • Domvanalimab
  • Etrumadenant

Eligibility Criteria

        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.
      
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:Through completion of treatment (estimated to be 9 months)
Safety Issue:
Description: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.

Secondary Outcome Measures

Measure: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)
Safety Issue:
Description:- Adverse events will be assessed using CTCAE v5.0 criteria
Measure: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)
Safety Issue:
Description:- Adverse events will be assessed using CTCAE v5.0 criteria
Measure:Progression-free survival (PFS)
Time Frame:Through completion of follow-up (estimated to be 5 years)
Safety Issue:
Description: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.
Measure:Duration of response (DoR)
Time Frame:Through completion of treatment (estimated to be 9 months)
Safety Issue:
Description: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.
Measure:Disease control rate (DCR)
Time Frame:Through completion of treatment (estimated to be 9 months)
Safety Issue:
Description: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.
Measure:Overall survival (OS)
Time Frame:Through completion of follow-up (estimated to be 5 years)
Safety Issue:
Description:- 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.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Washington University School of Medicine

Last Updated

May 25, 2021