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.

NCT06542250 | Recruiting Phase 1 FDA Drug

• 1 other identifier: D9960C00001
• Study Type: interventional
• Target: 174
• Locations: 10 countries
• Sites: 30

Brief Summary

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.

Conditions

B-cell Malignancies

Keywords

CD20; CD8; T cell engager; TCR; AZD5492; Relapsed, Refractory; B-cell malignancies; CLL, Chronic lymphocytic leukemia; SLL, Small lymphocytic lymphoma; MCL, Mantle cell lymphoma; LBCL, Large B-cell lymphoma; FL, Follicular lymphoma; TITANium; TCE

Outcome Measures

Primary Outcomes (3)

• Frequency of dose limiting toxicities (DLTs).

  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.

  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.

  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 Outcomes (12)

• Overall Response Rate (ORR)

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

• Complete Response Rate (CR Rate)

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

• Duration of Response (DoR)

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

• Progression-free Survival (PFS)

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

• Overall Survival (OS)

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

Study Arms (1)

Module 1: AZD5492 Monotherapy

EXPERIMENTAL

AZD5492 monotherapy for Relapsed or Refractory B-Cell Malignancies.

Drug: AZD5492

Interventions

AZD5492 DRUG

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

Module 1: AZD5492 Monotherapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• ≥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).

You may not qualify if:

• 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

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (30)

Research Site

La Jolla, California, 92093, United States

RECRUITING

Research Site

Boston, Massachusetts, 02215, United States

WITHDRAWN

Research Site

Rochester, Minnesota, 55905, United States

NOT YET RECRUITING

Research Site

Hackensack, New Jersey, 07601, United States

RECRUITING

Research Site

New York, New York, 10021, United States

RECRUITING

Research Site

New York, New York, 10029, United States

RECRUITING

Research Site

Charlotte, North Carolina, 28203, United States

RECRUITING

Research Site

Winston-Salem, North Carolina, 27157, United States

RECRUITING

Research Site

Houston, Texas, 77030, United States

RECRUITING

Research Site

Seattle, Washington, 98109, United States

RECRUITING

Research Site

Melbourne, 3000, Australia

RECRUITING

Research Site

Nedlands, 6009, Australia

RECRUITING

Research Site

Calgary, Alberta, T2N 5G2, Canada

RECRUITING

Research Site

Toronto, Ontario, M5G 2M9, Canada

RECRUITING

Research Site

Montreal, Quebec, H3T 1R2, Canada

RECRUITING

Research Site

Hangzhou, 310003, China

RECRUITING

Research Site

Shanghai, 200025, China

RECRUITING

Research Site

København Ø, 2100, Denmark

RECRUITING

Research Site

Pessac, 33604, France

RECRUITING

Research Site

Villejuif, 94805, France

RECRUITING

Research Site

München, 81675, Germany

RECRUITING

Research Site

Ulm, 89081, Germany

RECRUITING

Research Site

Würzburg, 97080, Germany

RECRUITING

Research Site

Bologna, 40138, Italy

RECRUITING

Research Site

Milan, 20133, Italy

RECRUITING

Research Site

Chūōku, 104-0045, Japan

RECRUITING

Research Site

Kashiwa, 277-8577, Japan

RECRUITING

Research Site

Barcelona, 08035, Spain

RECRUITING

Research Site

L'Hospitalet de Llobregat, 08908, Spain

RECRUITING

Research Site

Madrid, 28040, Spain

RECRUITING

MeSH Terms

Conditions

Recurrence; Leukemia, B-Cell; Leukemia, Lymphocytic, Chronic, B-Cell; Lymphoma, Mantle-Cell; Lymphoma, Follicular

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Chronic Disease; Lymphoma, Non-Hodgkin; Lymphoma

Central Study Contacts

AstraZeneca Clinical Study Information Center

CONTACT

1-877-240-9479; information.center@astrazeneca.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: The study consists of individual modules each evaluating the safety, tolerability, PK, immunogenicity, pharmacodynamics, and preliminary efficacy of AZD5492 as monotherapy or in combination with other anticancer treatments in participants with R/R B-cell malignancies. \- Module 1: AZD5492 Monotherapy

Study Record Dates

• First Submitted: July 29, 2024
• First Posted: August 7, 2024
• Study Start: September 18, 2024
• Primary Completion (Estimated): February 14, 2028
• Study Completion (Estimated): February 14, 2028
• Last Updated: May 1, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• 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/.
• 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.

Locations

AU (2); US (10); CA (3); IT (2); DE (3); JP (2); ES (3); DK (1); FR (2); CN (2)