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.

Phase 1

Recruiting

• Conditions: B-cell Malignancies
• Interventions: Drug: AZD5492

• Registration Number: NCT06542250
• Lead Sponsor: AstraZeneca

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2024-07-29
• Study First Submitted QC: 2024-08-02
• Study First Posted: 2024-08-07
• Study Start: 2024-09-18
• Status Verified: 2025-03
• Last Update Submitted: 2025-03-24
• Last Update Posted: 2025-03-26
• Primary Completion: 2028-02-14
• Study Completion: 2028-02-14

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 174

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Module 1: AZD5492 Monotherapy	AZD5492	AZD5492 monotherapy for Relapsed or Refractory B-Cell Malignancies.

Primary Outcome Measures

Name	Time	Method
Frequency of dose limiting toxicities (DLTs).	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.
Tolerability evaluation of AZD5492: Number of participants with treatment-related adverse events.	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.
Safety evaluation of AZD5492: Number of participants with treatment-related adverse events.	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

Secondary Outcome Measures

Name	Time	Method
Overall Response Rate (ORR)	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.
Complete Response Rate (CR Rate)	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.
Duration of Response (DoR)	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.
Progression-free Survival (PFS)	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.
Overall Survival (OS)	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.
Pharmacokinetics of AZD5492: serum concentration of study drug	Module 1 - From informed consent until 90 days after last dose of AZD5492.	Maximum observed serum concentration of AZD5492.
Pharmacokinetics of AZD5492: Maximum plasma concentration of the study drug (Cmax).	Module 1 - From informed consent until 90 days after last dose of AZD5492.	Maximum observed plasma concentration of AZD5492.
Pharmacokinetics of AZD5492: Area under the concentration time curve (AUC).	Module 1 - From informed consent until 90 days after last dose of AZD5492.	Area under the plasma concentration-time curve.
Pharmacokinetics of AZD5492: apparent clearance	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.
Pharmacokinetics of AZD5492: Half-life (t 1/2)	Module 1 - From informed consent until 90 days after last dose of AZD5492.	Terminal elimination half-life.
To determine the immunogenicity of AZD5492	Module 1 - From informed consent until 90 days after last dose of AZD5492.	The percentage of participants who develop ADAs measured in serum.

Trial Locations

Locations (1)

Research Site; 🇪🇸 Madrid, Spain