Clinical trial 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.
Official 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)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
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
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2024-08-07
Enrollment: 174
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
Intervention model description: 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
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Frequency of dose limiting toxicities (DLTs).
timeFrame: Module 1 - From the first administration of AZD5492 until the end of cycle 1 (up to 5 weeks).
measure: Safety evaluation of AZD5492: Number of participants with treatment-related adverse events.
timeFrame: 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.
measure: Tolerability evaluation of AZD5492: Number of participants with treatment-related adverse events.
timeFrame: 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:
measure: Overall Response Rate (ORR)
timeFrame: Module 1 - From first dose of AZD5492 up to 2 years after last dose.
measure: Complete Response Rate (CR Rate)
timeFrame: Module 1 - From first dose of AZD5492 up to 2 years after last dose.
measure: Duration of Response (DoR)
timeFrame: Module 1 - From first dose of AZD5492 up to 2 years after last dose.
measure: Progression-free Survival (PFS)
timeFrame: Module 1 - From first dose of AZD5492 up to 2 years after last dose.
measure: Overall Survival (OS)
timeFrame: Module 1 - From first dose of AZD5492 up to 2 years after last dose.
measure: Pharmacokinetics of AZD5492: serum concentration of study drug
timeFrame: Module 1 - From informed consent until 90 days after last dose of AZD5492.
measure: Pharmacokinetics of AZD5492: Maximum plasma concentration of the study drug (Cmax).
timeFrame: Module 1 - From informed consent until 90 days after last dose of AZD5492.
measure: Pharmacokinetics of AZD5492: Area under the concentration time curve (AUC).
timeFrame: Module 1 - From informed consent until 90 days after last dose of AZD5492.
measure: Pharmacokinetics of AZD5492: apparent clearance
timeFrame: Module 1 - From informed consent until 90 days after last dose of AZD5492.
measure: Pharmacokinetics of AZD5492: Half-life (t 1/2)
timeFrame: Module 1 - From informed consent until 90 days after last dose of AZD5492.
measure: To determine the immunogenicity of AZD5492
timeFrame: Module 1 - From informed consent until 90 days after last dose of AZD5492.
measure: To determine the immunogenicity of AZD5492
timeFrame: Module 1 - From informed consent until 90 days after last dose of AZD5492.
Other outcomes:
Locations:
city: La Jolla
country: United States
facility: Research Site
state: California
city: Boston
country: United States
facility: Research Site
state: Massachusetts
city: Hackensack
country: United States
facility: Research Site
state: New Jersey
city: New York
country: United States
facility: Research Site
state: New York
city: New York
country: United States
facility: Research Site
state: New York
city: Charlotte
country: United States
facility: Research Site
state: North Carolina
city: Winston-Salem
country: United States
facility: Research Site
state: North Carolina
city: Houston
country: United States
facility: Research Site
state: Texas
city: Seattle
country: United States
facility: Research Site
state: Washington
city: Melbourne
country: Australia
facility: Research Site
city: Nedlands
country: Australia
facility: Research Site
city: Calgary
country: Canada
facility: Research Site
state: Alberta
city: Toronto
country: Canada
facility: Research Site
state: Ontario
city: Montreal
country: Canada
facility: Research Site
state: Quebec
city: Hangzhou
country: China
facility: Research Site
city: Shanghai
country: China
facility: Research Site
city: København Ø
country: Denmark
facility: Research Site
city: Pessac
country: France
facility: Research Site
city: München
country: Germany
facility: Research Site
city: Ulm
country: Germany
facility: Research Site
city: Wuerzburg
country: Germany
facility: Research Site
city: Bologna
country: Italy
facility: Research Site
city: Milano
country: Italy
facility: Research Site
city: Chuo-ku
country: Japan
facility: Research Site
city: Kashiwa
country: Japan
facility: Research Site
city: Barcelona
country: Spain
facility: Research Site
city: L'Hospitalet de Llobregat
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
Study officials:
References: