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RecruitingInterventionalPhase 1/Phase 2

A Modular Phase I/II Open-label, Multicenter Study 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-cell Non-Hodgkin Lymphoma (B-NHL) (Lumi-NHL)

NCT ID: NCT07123454Sponsor: AstraZenecaLast updated: 2026-05-08

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

Arms & interventions

  • DrugAZD4512

    AZD4512 is an antibody-drug conjugate targeting cluster of differentiation 22 (CD22) that will be administered via IV infusion

Outcome measures

Primary

  • 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

    Time frame: Up to 4 weeks

  • 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

    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

  • Frequency of SAEs/AEs leading to discontinuation of AZD4512

    To assess the safety and tolerability of AZD4512 in participants with R/R B-NHL

    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

  • 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

    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

Secondary

  • Objective response rate (ORR)

    Time frame: Up to 2 years

  • Complete response (CR) rate

    Time frame: Up to 2 years

  • Duration of response (DoR)

    Time frame: Up to 2 years

  • Progression-free survival (PFS)

    Time frame: Up to 2 years

  • Overall survival (OS)

    Time frame: Up to 2 years

  • Area Under plasma concentration-time Curve (AUC) of AZD4512, total antibody and total unconjugated warhead

    Time frame: Up to 2 years

  • Observed plasma (peak) drug concentration (Cmax) of AZD4512, total antibody and total unconjugated warhead

    Time frame: Up to 2 years

  • Trough concentration (Ctrough) of AZD4512, total antibody and total unconjugated warhead

    Time frame: Up to 2 years

  • Half life of AZD4512, total antibody and total unconjugated warhead

    Time frame: Up to 2 years

  • Time to reach peak or maximum observed concentration (tmax) of AZD4512, total antibody and total unconjugated warhead

    Time frame: Up to 2 years

  • Total clearance of AZD4512, total antibody and total unconjugated warhead

    Time frame: Up to 2 years

  • The number and percentage of participants who develop anti-drug antibodies (ADAs)

    Time frame: Up to 2 years

Eligibility criteria

Sex: AllAge: 18 Years and olderHealthy volunteers: No
Key Inclusion Criteria: * Eligible patients must be adults (≥18 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, 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), 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 CYP3A4 inhibitors or (corrected QT interval - prolonging agents at C1, 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.

Study locations (8)

Research Site

Irvine, California, 92618

Recruiting

Research Site

Jacksonville, Florida, 32224

Recruiting

Research Site

Rochester, Minnesota, 55905

Recruiting

Research Site

New York, New York, 10016

Recruiting

Research Site

New York, New York, 10021

Recruiting

Research Site

Cleveland, Ohio, 44195

Withdrawn

Research Site

Myrtle Beach, South Carolina, 29572

Withdrawn

Research Site

Franklin, Tennessee, 37067

Recruiting