B-cell Non-Hodgkin Lymphoma
Conditions
Interventions
Drug: AZD4512
AZD4512 is an antibody-drug conjugate targeting cluster of differentiation 22 (CD22) that will be administered via IV infusion
Sponsors
Hibi Kazushige
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Eligible patients must be adults (18 or more years) - Documented diagnosis of B-cell non-Hodgkin lymphoma (B-NHL) as per World Health Organization (WHO) 2021 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), double/triple hit lymphomas, high-grade (B-cell lymphoma) BCL, primary mediastinal Large B-cell lymphoma (LBCL), and transformed indolent lymphoma), mantle cell lymphoma, and follicular lymphoma grades 1-3a. - Patients must have relapsed or refractory disease after at least two prior lines of therapy and lack additional standard options with survival 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. C)FL patients should have failed anti-CD20 with active disease requiring therapy. Additional criteria include measurable disease by Lugano 2014, Eastern Cooperative Oncology Group (ECOG) performance status 2 or less, and adequate organ and bone marrow functionas specified by blood counts, cardiac ejection fraction, renal and hepatic parameters, and coagulation indices.
Exclusion criteria
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), 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 or more months), autologous HSCT within 90 days (unless resolved toxicities), major surgery within 28 days, use of strong CYP3A4 inhibitors or (corrected QT interval - prolonging agents at C1, or other malignancies within two years. Patients with unresolved Grade 2 or more 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 |
|---|---|
| - Percentage of participants with dose-limiting toxicities (DLTs) [Time Frame: 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) [Time Frame: 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 [Time Frame: 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 - Number of participants with clinically significant alterations in vitals signs and abnormal laboratory parameters [Time Frame: 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 | — |
Countries
Australia, Italy, Japan, South Korea, Taiwan, United Kingdom, United Status
Contacts
Public ContactKazushige Hibi
Astrazeneka K.K
Outcome results
None listed