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NCT07123454PHASE1, PHASE2Recruiting

A Phase I/II Study of AZD4512 Monotherapy or in Combination With Anticancer Agents in Participants With Relapsed/Refractory B-cell Non-Hodgkin Lymphoma

AstraZeneca

Start Date

9/24/2025

Completion Date

3/1/2028

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

Eligibility Criteria

Age Range: 18 years to No maximum

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.

Interventions

DRUG

AZD4512

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Conditions

B-cell Non-Hodgkin Lymphoma

Locations

Research Site

Irvine, California 92618

United States

Research Site

Jacksonville, Florida 32224

United States

Research Site

Rochester, Minnesota 55905

United States

Research Site

New York, New York 10016

United States

Research Site

New York, New York 10021

United States

Research Site

Cleveland, Ohio 44195

United States

Research Site

Myrtle Beach, South Carolina 29572

United States

Research Site

Franklin, Tennessee 37067

United States

Research Site

Melbourne, 3000

Australia

Research Site

Chengdu, 610041

China

Research Site

Guangzhou, 510060

China

Research Site

Bologna, 40138

Italy

Research Site

Milan, 20133

Italy

Research Site

Milan, 20141

Italy

Research Site

Bunkyō City, 113-8677

Japan

Research Site

Kōtoku, 135-8550

Japan

Research Site

Seoul, 03080

South Korea

Research Site

Seoul, 5505

South Korea

Research Site

Taichung, 40705

Taiwan

Research Site

Taipei, 106

Taiwan

Research Site

London, W1T 7HA

United Kingdom

Research Site

Newcastle upon Tyne, NE7 7DN

United Kingdom