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. (TITANium)

April 30, 2026 updated by: AstraZeneca

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)

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

174

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Australia
      • Melbourne, Australia, 3000
        • Recruiting
        • Research Site
      • Nedlands, Australia, 6009
        • Recruiting
        • Research Site
  • Canada
    • Alberta
      • Calgary, Alberta, Canada, T2N 5G2
        • Recruiting
        • Research Site
    • Ontario
      • Toronto, Ontario, Canada, M5G 2M9
        • Recruiting
        • Research Site
    • Quebec
      • Montreal, Quebec, Canada, H3T 1R2
        • Recruiting
        • Research Site
  • China
      • Hangzhou, China, 310003
        • Recruiting
        • Research Site
      • Shanghai, China, 200025
        • Recruiting
        • Research Site
  • Denmark
      • København Ø, Denmark, 2100
        • Recruiting
        • Research Site
  • France
      • Pessac, France, 33604
        • Recruiting
        • Research Site
      • Villejuif, France, 94805
        • Recruiting
        • Research Site
  • Germany
      • München, Germany, 81675
        • Recruiting
        • Research Site
      • Ulm, Germany, 89081
        • Recruiting
        • Research Site
      • Würzburg, Germany, 97080
        • Recruiting
        • Research Site
  • Italy
      • Bologna, Italy, 40138
        • Recruiting
        • Research Site
      • Milan, Italy, 20133
        • Recruiting
        • Research Site
  • Japan
      • Chūōku, Japan, 104-0045
        • Recruiting
        • Research Site
      • Kashiwa, Japan, 277-8577
        • Recruiting
        • Research Site
  • Spain
      • Barcelona, Spain, 08035
        • Recruiting
        • Research Site
      • L'Hospitalet de Llobregat, Spain, 08908
        • Recruiting
        • Research Site
      • Madrid, Spain, 28040
        • Recruiting
        • Research Site
  • United States
    • California
      • La Jolla, California, United States, 92093
        • Recruiting
        • Research Site
    • Massachusetts
      • Boston, Massachusetts, United States, 02215
        • Withdrawn
        • Research Site
    • Minnesota
      • Rochester, Minnesota, United States, 55905
        • Not yet recruiting
        • Research Site
    • New Jersey
      • Hackensack, New Jersey, United States, 07601
        • Recruiting
        • Research Site
    • New York
      • New York, New York, United States, 10021
        • Recruiting
        • Research Site
      • New York, New York, United States, 10029
        • Recruiting
        • Research Site
    • North Carolina
      • Charlotte, North Carolina, United States, 28203
        • Recruiting
        • Research Site
      • Winston-Salem, North Carolina, United States, 27157
        • Recruiting
        • Research Site
    • Texas
      • Houston, Texas, United States, 77030
        • Recruiting
        • Research Site
    • Washington
      • Seattle, Washington, United States, 98109
        • Recruiting
        • Research Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Module 1: AZD5492 Monotherapy
AZD5492 monotherapy for Relapsed or Refractory B-Cell Malignancies.
Drug: AZD5492
CD8/TCR based T-cell engaging antibody targeting CD20, which is administered subcutaneously

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Module 1 - From the first administration of AZD5492 until the end of cycle 1 (up to 5 weeks).
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
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.
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.
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.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Module 1 - From informed consent until 90 days after last dose of AZD5492.
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.
Module 1 - From informed consent until 90 days after last dose of AZD5492.
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.
Module 1 - From informed consent until 90 days after last dose of AZD5492.
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.
Module 1 - From informed consent until 90 days after last dose of AZD5492.
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.
Module 1 - From informed consent until 90 days after last dose of AZD5492.
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.
Module 1 - From informed consent until 90 days after last dose of AZD5492.
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.
Module 1 - From informed consent until 90 days after last dose of AZD5492.
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.
Module 1 - From first dose of AZD5492 up to 2 years after last dose.
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.
Module 1 - From first dose of AZD5492 up to 2 years after last dose.
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.
Module 1 - From first dose of AZD5492 up to 2 years after last dose.
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.
Module 1 - From first dose of AZD5492 up to 2 years after last dose.
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.
Module 1 - From first dose of AZD5492 up to 2 years after last dose.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

AstraZeneca

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 18, 2024

Primary Completion (Estimated)

February 14, 2028

Study Completion (Estimated)

February 14, 2028

Study Registration Dates

First Submitted

July 29, 2024

First Submitted That Met QC Criteria

August 2, 2024

First Posted (Actual)

August 7, 2024

Study Record Updates

Last Update Posted (Actual)

May 1, 2026

Last Update Submitted That Met QC Criteria

April 30, 2026

Last Verified

April 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • D9960C00001

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD 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

Vivli.org. All requests will be evaluated as per the AZ disclosure commitment:

https://www.astrazenecaclinicaltrials.com/our-transparency-commitments/.

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

IPD Sharing Time Frame

AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA/PhRMA Data-Sharing Principles. For details of our timelines, please refer to our disclosure commitment at https://www.astrazenecaclinicaltrials.com/our-transparency-commitments/.

IPD Sharing Access Criteria

When a request has been approved AstraZeneca will provide access to the anonymized individual patient-level data via secure research environment Vivli.org. A Signed Data Usage Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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