Chronic Lymphocytic Leukaemia, Small Lymphocytic Lymphoma, Mantle-cell Lymphoma, Large B-cell Lymphoma, B-cell Non-Hodgkin Lymphoma
Conditions
Keywords
IgG4 fully human CD19xCD3 bispecific T-cell engager, B cell lymphoma, Subcutaneous, AZD0486, Acalabrutinib, Prednisone, Rituximab, Cyclophosphamide, Vincristine, Doxorubicin, Surovatamig
Brief summary
The purpose of this study is to assess the safety and efficacy of AZD0486 administered as monotherapy or in combination with other anticancer agents in participants with hematological malignancies.
Detailed description
This is open-label, multi-center study to evaluate the safety and preliminary efficacy of AZD0486 administered as monotherapy and in combination with other anticancer agents in participants with mature B-cell hematologic malignancies. This master study currently includes 3 substudies and each substudy focusing on a defined population: Substudy 1: Relapsed/refractory (R/R) Chronic lymphocytic leukaemia (CLL)/ Small lymphocytic lymphoma (SLL) Substudy 2: R/R Mantle-cell lymphoma (MCL) Substudy 3: Large B-cell lymphoma (LBCL) or R/R B-cell non-Hodgkin lymphoma (B-NHL) (not applicable to US) The study will have the following sequential periods: 1. Screening period of 28 days 2. Treatment period 3. Follow-up period
Interventions
DRUGAZD0486
AZD0486 will be administered as either SC injection or IV infusion.
Prednisone (or equivalent) will be administered either oral or IV infusion as per standard of care.
DRUGRituximab
Rituximab will be administered as IV infusion as per standard of care.
DRUGCyclophosphamide
Cyclophosphamide will be administered as IV infusion as per standard of care.
DRUGVincristine
Vincristine will be administered as IV infusion as per standard of care.
DRUGDoxorubicin
Doxorubicin will be administered as IV infusion as per standard of care.
DRUGAcalabrutinib
Acalabrutinib will be administered orally
Sponsors
AstraZeneca
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Master Inclusion Criteria applicable to all substudies: * Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2. * Contraception use during treatment and at least 90 days after final dose. * Confirmed CD19 expression if prior anti-CD19 therapy. Substudy 1 Specific Inclusion Criteria: * Participants with CLL must require treatment according to the international workshop on Chronic Lymphocytic Leukemia (iwCLL) criteria. * SLL: at least 1 measurable site per Lugano. * Absolute lymphocytes \<10,000. * Cohort 1A and 1C: at least 2 prior lines of systemic therapy for CLL/SLL. * Cohort 1B: at least 1 prior line of therapy and is bruton tyrosine kinase inhibitor (BTKi)-sensitive. Substudy 2 Specific Inclusion Criteria: * MCL diagnosis per WHO. * Clinical Stage II, III, or IV by Ann Arbor Classification. * At least 1 measurable site per Lugano. * ALC \< 10,000. * Cohort 2A and 2C: Relapse or progressed after 2 or more lines of therapy including BTKi. Substudy 3 Specific Inclusion Criteria: * Large B-cell lymphoma per WHO 2022. * R/R B-NHL after at least 1 prior line of therapy. * International Prognostic Index (IPI) 2-5. * At least 1 measurable site as per Lugano. * Left ventricular ejection fraction (LVEF) \>50%. * Contraception at least 90 days after last dose of AZD0486 or 4 months after last dose of vincristine, and 6 months after the last dose of cyclophosphamide, or doxorubicin.
Exclusion criteria
Master
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants with Adverse Events, Serious Adverse Events and Adverse Events of Special Interest | Up to 6 years 4 months | Safety and tolerability of AZD0486 as monotherapy and in combination with other anticancer agents across mature B-cell malignancies. |
| Number of Participants with Dose Limiting Toxicity (DLTs) | Up to 2 months | Safety and tolerability of AZD0486 as monotherapy and in combination with other anticancer agents across mature B-cell malignancies. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) | Up to 6 years 4 months | ORR is defined as percentage of participants achieving either a partial response (PR) or complete response (CR) based on response criteria for International Workshop on Chronic Lymphocytic Leukemia (iwCLL) 2018 and Lugano 2014 assessed by investigator (substudy 1) and percentage of participants achieving CR as best response based on Lugano 2014 Response Criteria by investigator assessment (substudies 2 and 3). |
| Complete Response (CR) Rate | Up to 6 years 4 months | CR rate is defined as percentage of participants achieving CR as best response based on response criteria for iwCLL 2018 and Lugano 2014 assessed by investigator (substudy 1) and percentage of participants achieving CR as best response based on Lugano 2014 Response Criteria by investigator assessment (substudies 2 and 3). |
| Duration of Response (DoR) | Up to 6 years 4 months | DoR is defined as time from the date of first documented response until date of documented progression based on response criteria for iwCLL 2018 and Lugano 2014 assessed by investigator, relapse or death (substudy 1) and time from the date of first documented response until date of documented progression based on Lugano 2014 Response Criteria by investigator assessment, relapse or death (substudies 2 and 3). |
| Maximum Observed Concentration (Cmax) | Up to 90 days after last dose | The PK (Cmax) of AZD0486 as monotherapy and in combination with other anti-cancer agents will be evaluated. |
| Area Under the Concentration-time Curve (AUC) | Up to 90 days after last dose | The PK (AUC) of AZD0486 as monotherapy and in combination with other anti-cancer agents will be evaluated. |
| Minimum Observed Concentration (Cmin) | Up to 90 days after last dose | The PK (Cmin) of AZD0486 as monotherapy and in combination with other anti-cancer agents will be evaluated. |
| Time to Reach Maximum Concentration (Tmax) | Up to 90 days after last dose | The PK (Tmax) of AZD0486 as monotherapy and in combination with other anti-cancer agents will be evaluated. |
| Trough Plasma Concentration (Ctrough) | Up to 90 days after last dose | The PK (Ctrough) of AZD0486 as monotherapy and in combination with other anti-cancer agents will be evaluated. |
| Half Life (t1/2) of AZD0486 | Up to 90 days after last dose | The PK (t1/2) of AZD0486 as monotherapy and in combination with other anti-cancer agents will be evaluated. |
| Clearance (CL) of AZD0486 | Up to 90 days after last dose | The PK (CL) of AZD0486 as monotherapy and in combination with other anti-cancer agents will be evaluated. |
| Number of Participants with Anti-drug Antibody (ADA) for AZD0486 | Up to 90 days after last dose | The incidence of immunogenicity of SC AZD0486 as monotherapy and in combination with other anti-cancer agents will be evaluated. |
Countries
Australia, China, Czechia, Denmark, France, Germany, Italy, Japan, South Korea, Spain, Taiwan, United Kingdom, United States
Contacts
CONTACTAstraZeneca Clinical Study Information Center
Outcome results
None listed