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NCT Number: NCT06542250

A Study to Evaluate Safety, PK, PD and Efficacy of AZD5492, a T Cell-engaging Antibody Targeting CD20 in Subjects With R/R B-Cell Malignancies.

This is a Phase I/II study designed to evaluate if experimental T cell engaging antibody targeting CD20 AZD5492 is safe, tolerable and efficacious in participants with Relapsed or Refractory B-Cell Malignancies.

Recruiting

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Key information

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • ≥18 years of age;
  • Histologically documented CD20+ mature B-cell neoplasm
  • Large B-cell lymphoma
  • Follicular lymphoma
  • Mantle cell lymphoma
  • Chronic lymphocytic leukemia
  • Small lymphocytic lymphoma
  • Relapsed, progressive and/or refractory disease following at least 2 prior lines of therapy;
  • ECOG performance status of ≤ 2 (< 2 in EU countries).

The above is a summary, other inclusion criteria details may apply.

Exclusion criteria

  • Any neoplasm histology not specified in the IC section;
  • Active CNS involvement in lymphoma;
  • CNS pathology including but not limited to any history of seizure disorder/epilepsy;
  • Prior allogeneic HSCT within 180 days, prior autologous HSCT within 90 days, or cell therapy within 90 days of start of therapy;
  • History of Grade ≥ 3 CRS or Grade ≥ 3 ICANS;
  • Active and uncontrolled infections;
  • Unresolved AEs ≥2 Grade due to prior anticancer therapies, with some exceptions

The above is a summary, other exclusion criteria details may apply.

Treatment and study plan

AZD5492

Drug

CD8/TCR based T-cell engaging antibody targeting CD20, which is administered subcutaneously

Primary outcomes

  1. Frequency of dose limiting toxicities (DLTs).

    Time frame: Module 1 - From the first administration of AZD5492 until the end of cycle 1 (up to 5 weeks).

    DLTs are dose-limiting toxicities as defined in the study protocol.

  2. Safety evaluation of AZD5492: Number of participants with treatment-related adverse events.

    Time frame: Module 1 - From the first administration of AZD5492 within the duration of the treatment period, up to and including 90 (+7) days after the last dose of study treatment , but prior to subsequent cancer therapy.

    Incidence and severity of AEs, AESIs, and SAEs

  3. Tolerability evaluation of AZD5492: Number of participants with treatment-related adverse events.

    Time frame: Module 1 - From the first administration of AZD5492 within the duration of the treatment period, up to and including 90 (+7) days after the last dose of study treatment , but prior to subsequent cancer therapy.

    SAEs/AEs leading to discontinuation of AZD5492.

Secondary outcomes

  1. Overall Response Rate (ORR)

    Time frame: Module 1 - From first dose of AZD5492 up to 2 years after last dose.

    The proportion of participants with a complete response or partial response, according to Lugano criteria for malignant lymphoma and iwCLL 2018 criteria for CLL.

  2. Complete Response Rate (CR Rate)

    Time frame: Module 1 - From first dose of AZD5492 up to 2 years after last dose.

    The proportion of participants with a complete response (CR), according to Lugano criteria for malignant lymphoma and iwCLL 2018 criteria for CLL.

  3. Duration of Response (DoR)

    Time frame: Module 1 - From first dose of AZD5492 up to 2 years after last dose.

    The time from the date of first documented response until the date of documented progression (according to Lugano criteria for malignant lymphoma and iwCLL 2018 criteria for CLL) or death due to any cause.

  4. Progression-free Survival (PFS)

    Time frame: Module 1 - From first dose of AZD5492 up to 2 years after last dose.

    The time from the date of first dose until the date of documented disease progression (according to Lugano criteria for malignant lymphoma and iwCLL 2018 criteria for CLL) or death due to any cause.

  5. Overall Survival (OS)

    Time frame: Module 1 - From first dose of AZD5492 up to 2 years after last dose.

    The time from the date of first dose until date of death due to any cause.

  6. Pharmacokinetics of AZD5492: serum concentration of study drug

    Time frame: Module 1 - From informed consent until 90 days after last dose of AZD5492.

    Maximum observed serum concentration of AZD5492.

  7. Pharmacokinetics of AZD5492: Maximum plasma concentration of the study drug (Cmax).

    Time frame: Module 1 - From informed consent until 90 days after last dose of AZD5492.

    Maximum observed plasma concentration of AZD5492.

  8. Pharmacokinetics of AZD5492: Area under the concentration time curve (AUC).

    Time frame: Module 1 - From informed consent until 90 days after last dose of AZD5492.

    Area under the plasma concentration-time curve.

  9. Pharmacokinetics of AZD5492: apparent clearance

    Time frame: Module 1 - From informed consent until 90 days after last dose of AZD5492.

    The volume of plasma from which the study drug is completely removed per unit time.

  10. Pharmacokinetics of AZD5492: Half-life (t 1/2)

    Time frame: Module 1 - From informed consent until 90 days after last dose of AZD5492.

    Terminal elimination half-life.

  11. To determine the immunogenicity of AZD5492

    Time frame: Module 1 - From informed consent until 90 days after last dose of AZD5492.

    The number of participants who develop ADAs measured in serum.

  12. To determine the immunogenicity of AZD5492

    Time frame: Module 1 - From informed consent until 90 days after last dose of AZD5492.

    The percentage of participants who develop ADAs measured in serum.

Study contacts

Contact information is provided by the study sponsor or research team.

AstraZeneca Clinical Study Information Center

CONTACT

[email protected]

1-877-240-9479

Sponsors and collaborators

Lead sponsor

AstraZeneca

Industry

Registry information

Official study title

A Modular Phase I/II Open-label Dose Escalation and Dose Expansion Study to Evaluate the Safety, Pharmacokinetics, Pharmacodynamics, and Efficacy of AZD5492, a T Cell-engaging Antibody Targeting CD20 in Subjects With Relapsed or Refractory B-Cell Malignancies (TITANium)

Acronym: TITANium

Important dates

Study start
2024
Primary completion
2029
Study completion
2029
First posted
Aug 7, 2024
Registry last updated
Jul 21, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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