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).
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 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.
Sequential
AZD4512
DrugAZD4512 is an antibody-drug conjugate targeting cluster of differentiation 22 (CD22) that will be administered via IV infusion
Percentage of participants with dose-limiting toxicities (DLTs)
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)
To assess the safety and tolerability of AZD4512 in participants with R/R B-NHL
Frequency of SAEs/AEs leading to discontinuation of AZD4512
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
To assess the safety and tolerability of AZD4512 in participants with R/R B-NHL
Objective response rate (ORR)
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
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)
DoR, according to Lugano classification 2024, to evaluate the preliminary efficacy of AZD4512 monotherapy in participants with R/R B-NHL.
Progression-free survival (PFS)
PFS, according to Lugano classification 2024, to evaluate the preliminary efficacy of AZD4512 monotherapy in participants with R/R B-NHL.
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