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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04931654
Recruitment Status : Recruiting
First Posted : June 18, 2021
Last Update Posted : June 23, 2022
Sponsor:
Information provided by (Responsible Party):
AstraZeneca

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Carcinoma, Non-Small-Cell Lung Drug: AZD7789 Phase 1 Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 81 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Intervention Model Description: This is a FTIH, multicenter, open-label, dose-escalation and dose-expansion study. The study includes 2 parts: Part A Dose Escalation and Part B Dose Expansion. Initially, participants with Stage IIIB to IV NSCLC will be enrolled in the study; additional tumor types may be explored and added in a future amendment to the CSP.
Masking: None (Open Label)
Primary Purpose: Treatment
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.
Actual Study Start Date : September 28, 2021
Estimated Primary Completion Date : January 23, 2025
Estimated Study Completion Date : July 1, 2025

Arm Intervention/treatment
Experimental: Dose Escalation Part A: NSCLC Immuno-oncology (IO) acquired or primary resistance
AZD7789 monotherapy
Drug: AZD7789
anti-PD-1 and anti-TIM-3 bispecific antibody

Experimental: Dose Expansion Part B1: NSCLC IO acquired resistance
AZD7789 Monotherapy
Drug: AZD7789
anti-PD-1 and anti-TIM-3 bispecific antibody

Experimental: Dose Expansion Part B2: NSCLC IO naive
AZD7789 Monotherapy
Drug: AZD7789
anti-PD-1 and anti-TIM-3 bispecific antibody




Primary Outcome Measures :
  1. 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 ]
    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

  2. Number of participants with dose-limiting toxicity (DLT), as defined in the protoocol [ Time Frame: From the first patient until the end of the dose escalation period; approximately 18 months. ]
    A DLT is a toxicity defined by the study protocol that occurs from the first dose of study intervention up to the end of the DLT evaluation period that is assessed as clearly unrelated to the primary disease or intercurrent illness.

  3. Preliminary anti-tumour activity of AZD7789 [ 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. ]
    Objective response rate as defined by RECIST v1.1


Secondary Outcome Measures :
  1. 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. ]
    Objective response rate as defined by RECIST v1.1

  2. Disease control rate [ Time Frame: From first documented response to confirmed progressive disease or death; approximate duration of 4 years. ]
    The percentage of participants according to RECIST v1.1 with a response or stable disease

  3. Duration of response [ Time Frame: From first documented response to confirmed progressive disease or death; approximate duration of 4 years. ]
    The time from first response according to RECIST v1.1 until progression or death

  4. Progression-free survival [ Time Frame: From first dose of study intervention to confirmed progressive disease or death; approximate duration of 4 years. ]
    The time from first dose of study intervention until the date of objective disease progression or death

  5. 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. ]
    The time from first dose of study intervention until death due to any cause

  6. 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. ]
    Maximum observed plasma concentration of the study drug.

  7. 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. ]
    The number and percentage of participants who develop detectable anti-drug antibodies (ADA).

  8. 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. ]
    Area under the plasma concentration-time curve.

  9. Pharmacokinetics of AZD7789: Clearance [ Time Frame: From first dose of study intervention, at predefined intervals throughout the administration of study intervention; approximately 4 years. ]
    A pharmacokinetic measurement of the volume of plasma from which the study drug is completely removed per unit time.

  10. 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. ]
    Terminal elimination half life.

  11. Preliminary anti-tumour activity of AZD7789: Changes in circulating tumor DNA (ctDNA) [ Time Frame: From first dose of study intervention, at predefined intervals throughout the administration of study intervention; approximately 4 years. ]
    Changes in ctDNA between baseline and on treatment.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 130 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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 archival or fresh tumor tissue sample and/or 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 at least one prior line of therapy contained approved anti-PD-1/PD-L1
  • Must have had immune-oncology (IO) acquired or primary resistance
  • PD-L1 expression < 1% or ≥ 1% documented

Part B Dose Expansion Cohort B1 Additional Inclusion Criteria:

  • May have squamous or 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:

  • May have squamous or 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 immune-mediated adverse event (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
  • History of symptomatic and objectively confirmed arterial (including myocardial infarction) or venous thromboembolic event within 6 months prior to the first dose of study intervention
  • History of organ transplant or allogenic haematopoietic stem cell 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-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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04931654


Contacts
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Contact: AstraZeneca Clinical Study Information Center 1-877-240-9479 information.center@astrazeneca.com

Locations
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United States, Georgia
Research Site Recruiting
Atlanta, Georgia, United States, 30322
United States, New York
Research Site Not yet recruiting
New York, New York, United States, 10029
United States, Tennessee
Research Site Recruiting
Nashville, Tennessee, United States, 37203
Canada, Ontario
Research Site Recruiting
Toronto, Ontario, Canada, M5G 2M9
France
Research Site Not yet recruiting
Bordeaux, France, 33076
Research Site Recruiting
Villejuif Cedex, France, 94805
Netherlands
Research Site Not yet recruiting
Amsterdam, Netherlands, 1066 CX
Spain
Research Site Recruiting
Barcelona, Spain, 08035
Research Site Recruiting
Madrid, Spain, 28027
Sponsors and Collaborators
AstraZeneca
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Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT04931654    
Other Study ID Numbers: D9570C00001
2021-000036-57 ( EudraCT Number )
152970 ( Registry Identifier: IND )
First Posted: June 18, 2021    Key Record Dates
Last Update Posted: June 23, 2022
Last Verified: June 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description:

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal.

All request will be evaluated as per the AZ disclosure commitment:

https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.

Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
Access Criteria: When a request has been approved AstraZeneca will provide access to the deidentified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
URL: https://astrazenecagroup-dt.pharmacm.com/DT/Home

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by AstraZeneca:
solid tumor
Non-small cell lung cancer
NSCLC
anti-PD-1/PD-L1
anti-TIM-3
Additional relevant MeSH terms:
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Carcinoma, Non-Small-Cell Lung
Carcinoma, Bronchogenic
Bronchial Neoplasms
Lung Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases