B-cell Non-Hodgkin Lymphoma
Conditions
Keywords
AZD4512, Non-Hodgkin Lymphoma (NHL), Relapsed/Refractory
Brief summary
This is a Phase I/II open-label, global multicenter study to evaluate the safety and efficacy of AZD4512 monotherapy or in combination with other anticancer agent(s), in participants with Relapsed/Refractory B-cell Non-Hodgkin Lymphoma (B-NHL).
Detailed description
Study D9890C00001 (Lumi-NHL) is modular study designed to evaluate the safety, pharmacokinetics, pharmacodynamics, immunogenicity, and efficacy of AZD4512 monotherapy or in combination with other anticancer agent(s), in participants with Relapsed/Refractory B-NHL. Module 1 aims to study AZD4512 monotherapy at in participants in R/R B-NHL who have been exposed to at least 2 prior lines of therapy. Additional modules in specific B-NHL subtypes with AZD4512 as monotherapy or in combination with other anticancer agent(s) may be added in the future
Interventions
DRUGAZD4512
AZD4512 is an antibody-drug conjugate targeting cluster of differentiation 22 (CD22) that will be administered via IV infusion
Sponsors
AstraZeneca
Study design
Allocation
NON_RANDOMIZED
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 AZD4512 as monotherapy or in combination with other anticancer treatments in participants with R/R B-NHL \- Module 1: AZD4512 Monotherapy.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Eligible patients must be adults (≥18 years) * Documented histologically confirmed diagnosis of B-cell non-Hodgkin lymphoma (B-NHL) as per World Health Organization (WHO) 2022 classification. In the dose escalation phase, any B-NHL subtype is allowed (excluding some subtypes), while the backfill phase restricts inclusion to defined subtypes: large B-cell lymphomas (as defined as Diffuse large B-cell lymphoma (DLBCL), Grade 3b Follicular lymphoma (FL), high-grade B-cell lymphoma (HGBCL) NOS, DLBCL/HGBCL with MYC and BCL2 rearrangements, primary mediastinal Large B-cell lymphoma, T-cell/histiocyte-rich LBCL, and transformed indolent lymphoma) and mantle cell lymphoma. * Patients must have relapsed or refractory disease after at least two prior lines of systemic therapy and lack additional standard options with established benefit: A)LBCL patients must have progressed after both anti-CD20 and at least one systemic chemotherapy regimen, and have considered-or be ineligible for-CAR-T, T cell engager, and stem cell transplant modalities. B) Mantle cell lymphoma (MCL) patients must have had anti-CD20 and Bruton's Tyrosine Kinase (BTK) inhibitor. Additional criteria include measurable disease by Lugano 2014, Eastern Cooperative Oncology Group (ECOG) performance status ≤2, and adequate organ and bone marrow function (as specified by blood counts, cardiac ejection fraction, renal and hepatic parameters, and coagulation indices). Key
Exclusion criteria
* Patients are excluded if they have a diagnosis of post-transplant lymphoproliferative disease, Richter's transformation, Burkitt's lymphoma, or chronic lymphocytic leukemia (CLL)/ Small lymphocytic lymphoma (SLL), Waldenstrom Macroglobulinemia/ Lymphoplasmacytic Lymphoma, or if they have active Central nervous system (CNS) involvement from their B-NHL. Exclusion also applies to those who have received Chimeric antigen receptor-T (CAR-T) or T cell engager therapies within 90 days prior to Cycle 1 Day 1 (C1D1), any investigational drug or other systemic anticancer therapies (except low-dose corticosteroids) within 21 days or 5 half-lives, and curative radiation within 14 days (localized palliative radiotherapy is allowed). * Other exclusions include allogeneic Hematopoietic stem cell transplantation (HSCT) within 180 days (unless stable without active (graft-versus-host disease) GVHD for ≥2 months), autologous HSCT within 90 days (unless resolved toxicities), major surgery within 28 days, use of strong CYP3A inhibitors within 14 days or 5 half-lives before the dosing date, use of QTc-prolonging agents within 5 half-lives before the dosing date, or other malignancies within two years. Patients with unresolved ≥ Grade 2 AEs from prior therapy (except specified tolerable conditions), serious uncontrolled medical conditions, active infection within 14 days, or history/suspicion of significant interstitial lung disease/pneumonitis are also excluded. * Females who are pregnant or breastfeeding are not eligible.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of participants with clinically significant alterations in vitals signs and abnormal laboratory parameters | From the first dose up to and including 30 (+7) days after the last dose of study treatment , but prior to subsequent cancer therapy | To assess the safety and tolerability of AZD4512 in participants with R/R B-NHL |
| Percentage of participants with dose-limiting toxicities (DLTs) | Up to 4 weeks | To identify the maximum tolerated dose (MTD) and/or doses of AZD4512 for subsequent evaluation in participants with R/R B-NHL |
| Frequency, duration, severity of Treatment-Emergent Adverse Events (TEAEs) and Treatment-Related Adverse Events (TRAEs) and Serious Adverse Events (SAEs) | From the first dose up to and including 30 (+7) days after the last dose of study treatment , but prior to subsequent cancer therapy | To assess the safety and tolerability of AZD4512 in participants with R/R B-NHL |
| Frequency of SAEs/AEs leading to discontinuation of AZD4512 | From the first dose up to and including 30 (+7) days after the last dose of study treatment , but prior to subsequent cancer therapy | To assess the safety and tolerability of AZD4512 in participants with R/R B-NHL |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free survival (PFS) | Up to 2 years | PFS, according to Lugano classification 2024, to evaluate the preliminary efficacy of AZD4512 monotherapy in participants with R/R B-NHL. |
| Overall survival (OS) | Up to 2 years | OS, defined as the time from the date of first dose until date of death, to evaluate the preliminary efficacy of AZD4512 monotherapy in participants with R/R B-NHL. |
| Area Under plasma concentration-time Curve (AUC) of AZD4512, total antibody and total unconjugated warhead | Up to 2 years | To characterize the AUC of AZD4512 as monotherapy in participants with R/R B-NHL |
| Observed plasma (peak) drug concentration (Cmax) of AZD4512, total antibody and total unconjugated warhead | Up to 2 years | To characterize the Cmax of AZD4512 as monotherapy in participants with R/R B-NHL |
| Trough concentration (Ctrough) of AZD4512, total antibody and total unconjugated warhead | Up to 2 years | To characterize the Ctrough of AZD4512 as monotherapy in participants with R/R B-NHL |
| Half life of AZD4512, total antibody and total unconjugated warhead | Up to 2 years | To characterize the Half life of AZD4512 as monotherapy in participants with R/R B-NHL |
| Time to reach peak or maximum observed concentration (tmax) of AZD4512, total antibody and total unconjugated warhead | Up to 2 years | To characterize the Tmax of AZD4512 as monotherapy in participants with R/R B-NHL |
| Total clearance of AZD4512, total antibody and total unconjugated warhead | Up to 2 years | To characterize the Total clearance of AZD4512 as monotherapy in participants with R/R B-NHL |
| The number and percentage of participants who develop anti-drug antibodies (ADAs) | Up to 2 years | To determine the immunogenicity of AZD4512 as monotherapy in participants with R/R B-NHL |
| Objective response rate (ORR) | Up to 2 years | ORR, according to Lugano classification 2024, to evaluate the preliminary efficacy of AZD4512 monotherapy in participants with R/R B-NHL. |
| Complete response (CR) rate | Up to 2 years | CR rate, according to Lugano classification 2024, to evaluate the preliminary efficacy of AZD4512 monotherapy in participants with R/R B-NHL. |
| Duration of response (DoR) | Up to 2 years | DoR, according to Lugano classification 2024, to evaluate the preliminary efficacy of AZD4512 monotherapy in participants with R/R B-NHL. |
Countries
Australia, China, Italy, Japan, South Korea, Taiwan, United Kingdom, United States
Contacts
CONTACTAstraZeneca Clinical Study Information Center
Outcome results
None listed