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A Study to Assess the Safety and Efficacy of AZD7789 in Participants With Advanced or Metastatic Solid Cancer

NCT04931654

Description:

This is a Phase I/IIa study designed to evaluate if experimental anti-PD-1 and anti-TIM-3 bispecific antibody, AZD7789 is safe, tolerable and efficacious in participants with advanced solid tumors.

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

Not yet recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Study to Assess the Safety and Efficacy of AZD7789 in Participants With Advanced or Metastatic Solid Cancer
  • Official Title: A Phase I/IIa Open-label Dose Escalation and Expansion Study to Evaluate the Safety, Pharmacokinetics, Pharmacodynamics, and Efficacy of AZD7789, an Anti-PD-1 and Anti-TIM-3 Bispecific Antibody, in Participants With Advanced or Metastatic Solid Tumors

Clinical Trial IDs

  • ORG STUDY ID: D9570C00001
  • SECONDARY ID: 2021-000036-57
  • SECONDARY ID: 152970
  • NCT ID: NCT04931654

Conditions

  • Carcinoma, Non-Small-Cell Lung

Interventions

DrugSynonymsArms
AZD7789Dose Escalation Part A: Non small cell lung cancer (NSCLC) Immuno-oncology (IO) acquired resistance

Purpose

This is a Phase I/IIa study designed to evaluate if experimental anti-PD-1 and anti-TIM-3 bispecific antibody, AZD7789 is safe, tolerable and efficacious in participants with advanced solid tumors.

Detailed Description

      This first time in patients, open-label, multi-centre study will have AZD7789 administered
      intravenously (IV) to participants with advanced solid tumors. This study will have 2 parts:
      Part A which will have dose escalation cohorts and Part B which will have the dose expansion
      cohorts.
    

Trial Arms

NameTypeDescriptionInterventions
Dose Escalation Part A: Non small cell lung cancer (NSCLC) Immuno-oncology (IO) acquired resistanceExperimentalAZD7789 monotherapy
  • AZD7789
Dose Expansion Part B1: NSCLC IO acquired resistanceExperimentalAZD7789 Monotherapy
  • AZD7789
Dose Expansion Part B2: NSCLC IO naiveExperimentalAZD7789 Monotherapy
  • AZD7789

Eligibility Criteria

        Inclusion Criteria:

          -  Must be ≥ 18 years of age

          -  Histologically or cytologically documented Stage IIIB to IV non-small cell lung
             carcinoma (NSCLC) not amenable to curative surgery or radiation

          -  Must have at least one measurable lesion according to Response Evaluation Criteria in
             Solid Tumors (RECIST) v1.1

          -  Provision of fresh tumor tissue sample and consent to undergo mandatory on-treatment
             biopsy for participants enrolled in Part A Dose-escalation

          -  Provision of archival tumor tissue sample or fresh tissue sample for Part B
             Dose-expansion participants

          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

          -  Non-pregnant women and willingness of female participants to avoid pregnancy or male
             participants willing to avoid fathering children through highly effective methods of
             contraception

          -  Adequate organ and bone marrow function measured within 28 days prior to first dose

        Part A Dose Escalation Additional Inclusion Criteria:

          -  May have squamous or non-squamous NSCLC

          -  Must have received at least one prior line of systemic therapy, of which only one
             prior line of therapy contained approved anti-PD-1/PD-L1

          -  Must have had immune-oncology (IO) acquired resistance

          -  PD-L1 TPS ≥ 1% documented

        Part B Dose Expansion Cohort B1 Additional Inclusion Criteria:

          -  Must have non-squamous NSCLC

          -  Must have received at least one but no more than 2 prior lines of systemic therapy, of
             which only one prior line of therapy contained approved anti-PD-1/PD-L1

          -  Must have had IO acquired resistance

          -  PD- L1 TPS ≥ 1% documented

        Part B Dose Expansion Cohort B2 Additional Inclusion Criteria:

          -  Must have non-squamous NSCLC

          -  Must not have received prior systemic therapy including IO therapy in the first-line
             setting

          -  PD-L1 TPS ≥ 50% documented

        Exclusion Criteria:

          -  Patients with sensitizing epidermal growth factor receptor (EGFR) mutations or
             anaplastic lymphoma kinase (ALK) fusions

          -  Documented test result for any other known genomic alteration for which a targeted
             first line therapy is approved per local standard of care (SoC)

          -  Unresolved toxicities of ≥ Grade 2 from prior therapy

          -  Any prior ≥ Grade 3 imAE while receiving immunotherapy or any unresolved imAE ≥ Grade
             2

          -  Must not have experienced a toxicity that led to permanent discontinuation of prior
             immunotherapy

          -  Symptomatic central nervous system (CNS) metastasis or leptomeningeal disease

          -  Any venous or arterial thromboembolic event within 6 months prior to study drug dosing

          -  History of organ transplant

          -  Infectious disease exclusions: Active infection including TB, HIV, hepatitis A,
             chronic or active hepatitis B, chronic or active hepatitis C, active COVID-19
             infection

          -  History of arrhythmia which is symptomatic or requires treatment; symptomatic or
             uncontrolled atrial fibrillation despite treatment, or asymptomatic sustained
             ventricular tachycardia

          -  Uncontrolled intercurrent illness including, but not limited to, ongoing or active
             infection, cardiomyopathy of any etiology, symptomatic congestive heart failure,
             uncontrolled hypertension, uncontrolled diabetes mellitus, unstable angina pectoris,
             history of myocardial infarction within the past 6 months, serious chronic
             gastrointestinal conditions associated with diarrhea, active non infectious skin
             disease

          -  Active or prior documented autoimmune or inflammatory disorders, including
             inflammatory bowel disease (eg, colitis or Crohn's disease), diverticulitis (with the
             exception of diverticulosis), systemic lupus erythematosus, Sarcoidosis syndrome, or
             Wegener syndrome (granulomatosis with polyangiitis), Graves' disease, rheumatoid
             arthritis, hypophysitis, uveitis, etc.. Some exceptions have been specified in the
             protocol

          -  Past medical history of interstitial lung disease (ILD), drug-induced ILD, radiation
             pneumonitis requiring steroid treatment, or any evidence of clinically active ILD

          -  Major surgical procedure within 28 days prior to the first dose of study intervention
             or still recovering from prior surgery

          -  Other invasive malignancy within 2 years prior to screening

          -  Congenital long QT syndrome or history of QT prolongation associated with other
             medications that cannot be changed or discontinued based on a cardiologist assessment

          -  Previous treatment with anti-CTLA-4 or anti-TIM-3 therapy in any setting

          -  Current or prior use of immunosuppressive medication within 14 days prior to the first
             dose of study intervention

          -  Any concurrent chemotherapy, radiotherapy, investigational, biologic, or hormonal
             therapy for cancer treatment. Concurrent use of hormonal therapy for noncancer-related
             conditions is acceptable.

          -  Receipt of live attenuated vaccine within 30 days prior to the first dose of study
             intervention. Note: Participants should not receive live vaccine while receiving study
             intervention and up to 30 days after the last dose of study intervention

          -  Radiotherapy treatment to the lung within ≤ 4 weeks of the first dose of AZD7789.
             Palliative bone radiotherapy is allowed if ≥ 2 weeks prior to the first dose of
             AZD7789.
      
Maximum Eligible Age:130 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Number of participants with adverse events (AE), serious adverse events (SAE) and immune-mediated AEs (imAE)
Time Frame:From time of Informed Consent to 90 days post last dose of study intervention
Safety Issue:
Description:Number of participants with AEs, SAEs, imAEs including AEs leading to discontinuation of study intervention and clinically significant alterations in vital signs, laboratory parameters and ECG results

Secondary Outcome Measures

Measure:Objective response rate
Time Frame:From first participant until last participant assessment; a duration of approximately 4 years. Disease assessments will be performed until progression or initiation of another anticancer therapy.
Safety Issue:
Description:Objective response rate as defined by RECIST v1.1
Measure:Disease control rate
Time Frame:From first documented response to confirmed progressive disease or death; approximate duration of 4 years.
Safety Issue:
Description:The percentage of participants according to RECIST v1.1 with a response or stable disease
Measure:Duration of response
Time Frame:From first documented response to confirmed progressive disease or death; approximate duration of 4 years.
Safety Issue:
Description:The time from first response according to RECIST v1.1 until progression or death
Measure:Progression-free survival
Time Frame:From first dose of study intervention to confirmed progressive disease or death; approximate duration of 4 years.
Safety Issue:
Description:The time from first dose of study intervention until the date of objective disease progression or death
Measure:Overall survival
Time Frame:From first dose of study intervention to death. Overall survival will be monitored for the duration of the study, which will last approximately 4 years.
Safety Issue:
Description:The time from first dose of study intervention until death due to any cause
Measure:Pharmacokinetics of AZD7789: Maximum plasma concentration of the study drug (Cmax)
Time Frame:From first dose of study intervention, at predefined intervals throughout the administration of study intervention; approximately 4 years.
Safety Issue:
Description:Maximum observed plasma concentration of the study drug.
Measure:Immunogenicity of AZD7789
Time Frame:From first dose of study intervention, at predefined intervals throughout the administration of study intervention. A duration of approximately 4 years.
Safety Issue:
Description:The number and percentage of participants who develop detectable anti-drug antibodies (ADA).
Measure:Pharmacokinetics of AZD7789: Area Under the concentration-time curve (AUC)
Time Frame:From first dose of study intervention, at predefined intervals throughout the administration of study intervention; approximately 4 years.
Safety Issue:
Description:Area under the plasma concentration-time curve.
Measure:Pharmacokinetics of AZD7789: Clearance
Time Frame:From first dose of study intervention, at predefined intervals throughout the administration of study intervention; approximately 4 years.
Safety Issue:
Description:A pharmacokinetic measurement of the volume of plasma from which the study is completely removed per unit time.
Measure:Pharmacokinetics of AZD7789: Terminal elimination half-life (t 1/2)
Time Frame:From first dose of study intervention, at predefined intervals throughout the administration of study intervention; approximately 4 years.
Safety Issue:
Description:Terminal elimination half life.

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:AstraZeneca

Trial Keywords

  • solid tumor
  • Non-small cell lung cancer
  • NSCLC
  • anti-PD-1/PD-L1
  • anti-TIM-3

Last Updated

July 16, 2021