Study of AZD5863 in Adult Participants With Advanced or Metastatic Solid Tumors

NCT06005493
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Phase
Phase 1/Phase 2
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Recruitment status
Recruiting
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Participants
392
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Lead sponsor
AstraZeneca
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Start date
2023-07-11
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Number of sites
25
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Summary
This research is designed to determine if experimental treatment with AZD5863, a T cell-engaging bispecific antibody that targets Claudin 18.2 (CLDN18.2) and CD3, is safe, tolerable and has anti-cancer activity in patients with advanced solid tumors.
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Short title
Study of AZD5863 in Adult Participants With Advanced or Metastatic Solid Tumors
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Official title
A Phase I/II Open-label Dose Escalation and Dose Expansion Study to Evaluate the Safety, Pharmacokinetics, Pharmacodynamics, and Efficacy of AZD5863, a T Cell-engaging Bispecific Antibody That Targets Claudin 18.2 (CLDN18.2) and CD3 in Adult Participants With Advanced or Metastatic Solid Tumors
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Control arm
Open label
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Registry reports results
No
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Listing at source
Listed
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Recruitment status
Recruiting
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Phase
Phase 1/Phase 2
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Study type
Interventional
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Completion date
2029-03-16
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First posted
2023-08-22
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Registry last updated
2026-09-25
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Primary completion date
2029-03-16
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Start date
2023-07-11
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Participants
392
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Participant count basis
Estimated
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Planned participants
392
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Protocol amendments
4
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Number of sites
25
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Data monitoring committee
No
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Registry sponsor category
Industry
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Lead sponsor
AstraZeneca
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Source registry
ClinicalTrials.gov
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Registry ID
NCT06005493
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ClinicalTrials.gov ID
NCT06005493
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Registry record
Open registry record
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Allocation
Randomised
Model
Sequential
Purpose
Treatment
Masking
No masking
Sources for study design
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  1. The number of patients with adverse events

    Timeframe: From first dose of study drug up to 90 days post last dose and prior to start of subsequent anticancer therapy

    Number of patients with adverse events by system organ class and preferred term

  2. The number of patients with adverse events of special interest

    Timeframe: From first dose of study drug up to 90 days post last dose and prior to start of subsequent anticancer therapy

    Number of patients with adverse events of special interest by system organ class and preferred term

  3. The number of patients with dose-limiting toxicity (DLT), as defined in the protocol.

    Timeframe: From first dose of study drug until the end of Cycle 1

    A DLT is a toxicity as defined in the protocol that occurs from the first dose of study drug up to and including the planned end of Cycle 1 (the DLT assessment period) that is assessed as unrelated to the disease or disease-related processes under investigation.

  4. The number of patients with serious adverse events

    Timeframe: From first dose of study drug up to 90 days post last dose and prior to start of subsequent anticancer therapy

    Number of patients with serious adverse events by system organ class and preferred term

  5. Objective Response Rate (ORR)

    Timeframe: From first dose of study drug to progressive disease or death in the absence of disease progression (approx. 2 years)

    The percentage of patients with a confirmed investigator assessed complete or partial response according to response criteria in solid tumours (RECIST 1.1). Dose expansion only.

  1. Objective Response Rate (ORR)

    Timeframe: From first dose of study drug to progressive disease or death in the absence of disease progression (approx. 2 years)

    The percentage of patients with a confirmed investigator assessed complete or partial response according to response criteria in solid tumours (RECIST 1.1). Dose escalation only.

  2. Disease Control Rate (DCR)

    Timeframe: From first dose of study drug to progressive disease or death in the absence of disease progression (approx. 2 years)

    Percentage of patients with confirmed complete or partial response or having stable disease maintained for \>= 11 weeks from first dose, according to response criteria in solid tumours (RECIST 1.1).

  3. Duration of response (DoR)

    Timeframe: From the first documented response to progressive disease or death in the absence of disease progression (approx. 2 years)

    The time from the date of first response until date of disease progression or death in the absence of disease progression, according to response criteria in solid tumours (RECIST 1.1).

  4. Progression free Survival (PFS)

    Timeframe: From the start of study treatment/date of randomization to progressive disease or death in the absence of disease progression (approx. 2 years)

    The time from the start of study treatment/date of randomization until RECIST 1.1 defined disease progression or death in the absence of disease progression.

  5. Overall Survival (OS)

    Timeframe: From the start of study treatment/date of randomization to death (to be followed-up for approx. 2 years)

    The time from the start of study treatment/date of randomization until death due to any cause.

  6. Pharmacokinetics of AZD5863: Maximum plasma concentration of the study drug (Cmax)

    Timeframe: From the first dose of study intervention, at predefined intervals throughout the study (approx. 2 years)

    Maximum observed plasma concentration of the study drug

  7. Pharmacokinetics of AZD5863: Area Under the concentration-time curve (AUC)

    Timeframe: From the first dose of study intervention, at predefined intervals throughout the study (approx. 2 years)

    Area under the plasma concentration-time curve

  8. Pharmacokinetics of AZD5863: Clearance

    Timeframe: From the first dose of study intervention, at predefined intervals throughout the study (approx. 2 years)

    A pharmacokinetic measurement of the volume of plasma from which the study drug is completely removed per unit time.

  9. Pharmacokinetics of AZD5863: Terminal elimination half-life (t 1/2)

    Timeframe: From the first dose of study intervention, at predefined intervals throughout the study (approx. 2 years)

    Terminal elimination half life.

  10. Immunogenicity of AZD5863

    Timeframe: From the first dose of study intervention, at predefined intervals throughout the study (approx. 2 years)

    The number and percentage of participants who develop anti-drug antibodies (ADAs) measured in serum

  11. Preliminary antitumor activity with target expression pre- and post-delivery of AZD5863

    Timeframe: From time of Informed consent, at predefined intervals (including screening, on-treatment or end of treatment) throughout the study (over approx. 2 years)

    Measure CLDN18.2 expression (IHC) in baseline and/or on-treatment tumor biopsies and correlate with clinical outcome

Sources for outcomes
clinicaltrials.gov

Sex
All
Age groups
Adults, Older adults
Minimum age
18 Years
Healthy volunteers
No

Key Inclusion Criteria:

  • Age ≥ 18 at the time of signing the informed consent
  • Histologically confirmed diagnosis of adenocarcinoma of the stomach, gastro-esophageal junction, esophagus, or pancreas
  • Must have at least one measurable lesion according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
  • Must show positive CLDN18.2 expression in tumor cells as determined by central immunohistochemistry (IHC)
  • Eastern Cooperative Oncology Group Performance status (ECOG PS): 0-1 at screening
  • Predicted life expectancy of ≥ 12 weeks
  • Adequate organ and bone marrow function measured within 28 days prior to first dose as defined by the protocol
  • Contraceptive use by men or women should be consistent with local regulations, as defined by the protocol
  • Must have received at least one prior line of systemic therapy in the advanced/metastatic setting

Key Exclusion Criteria:

  • Unresolved toxicity from prior anticancer therapy of Common Terminology Criteria for Adverse Events (CTCAE) Grade ≥ 2 except for those defined by the protocol
  • Participant experienced unacceptable cytokine release syndrome (CRS) or Immune Effector Cell Associated Neurotoxicity (ICANS) following prior T cell engagers (TCE) or chimeric antigen receptor T (CAR-T) cell therapy
  • Previous history of hemophagocytic lymphohistiocytosis (HLH) / macrophage activation syndrome (MAS)
  • Active or prior documented autoimmune or inflammatory disorders within 3 years of start of treatment
  • central nervous system (CNS) metastases or CNS pathology, as defined by the protocol, within 3 months prior to consent
  • Infectious disease including active human immunodeficiency virus (HIV), active hepatitis B/C, uncontrolled infection with EBV, uncontrolled active systemic fungal, bacterial or other infection
  • Cardiac conditions as defined by the protocol
  • History of thromboembolic event within the past 3 months prior to the scheduled first dose of study intervention
  • Participant requires chronic immunosuppressive therapy
  • Participants on anticoagulation therapy with long-acting anticoagulants or other class of anticoagulants at therapeutic doses Module 3 - Active or ongoing interstitial lung disease / pneumonitis, serious chronic gastrointestinal conditions Module 3 - Any of the following cardiac conditions as determined by investigator: Complex ventricular arrhythmia, symptomatic heart failure, Cardiomyopathy, myocardial infarction or unstable angina (within past 6 months) and uncontrolled hypertension.

Module 3 - Known allergy or hypersensitivity to rilvegostomig or its excipients Module 3 - Prior exposure to an anti-TIGIT therapy

Sources for eligibility
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  • Research SiteJacksonville, United StatesRecruiting
  • Research SiteRochester, United StatesRecruiting
  • Research SiteNew York, United StatesWithdrawn
  • Research SiteBeijing, ChinaRecruiting
  • Research SiteBeijing, ChinaRecruiting
  • Research SiteShandong, ChinaRecruiting
  • Research SiteToulouse, FranceRecruiting
  • Research SiteVillejuif, FranceRecruiting
  • Research SiteChūōku, JapanRecruiting
  • Research SiteKashiwa, JapanRecruiting
  • Research SiteKōtoku, JapanRecruiting
  • Research SiteAmsterdam, NetherlandsRecruiting
  • Research SiteGroningen, NetherlandsRecruiting
  • Research SiteRotterdam, NetherlandsRecruiting
  • Research SiteSeoul, South KoreaRecruiting
  • Research SiteSeoul, South KoreaRecruiting
  • Research SiteSeoul, South KoreaRecruiting
  • Research SiteSeoul, South KoreaRecruiting
  • Research SiteKaohsiung City, TaiwanRecruiting
  • Research SiteTainan, TaiwanRecruiting
  • Research SiteTaoyuan, TaiwanRecruiting
  • Research SiteDundee, United KingdomRecruiting
  • Research SiteLondon, United KingdomRecruiting
  • Research SiteMetropolitan Borough of Wirral, United KingdomRecruiting
  • Research SiteOxford, United KingdomRecruiting
Sources for sites
clinicaltrials.gov

  • 2023
  • 2023-504139-42-00
  • 2023-000154-20
Sources for references
clinicaltrials.gov

Related records

Drugs (1)

Lead sponsors (1)

Conditions (4)