B-cell Malignancies
Conditions
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
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.
Interventions
DRUGAZD5492
CD8/TCR based T-cell engaging antibody targeting CD20, which is administered subcutaneously
Sponsors
AstraZeneca
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
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
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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 |
| 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 number of participants who develop ADAs measured in serum. |
Countries
Australia, Canada, China, Denmark, France, Germany, Italy, Japan, Spain, United States
Contacts
CONTACTAstraZeneca Clinical Study Information Center
Outcome results
None listed