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

AstraZeneca

Status and phase: Begins enrollment in 2 months; Phase 2; Phase 1

Conditions: B-cell Non-Hodgkin Lymphoma

Treatments: Drug: AZD4512

Study type: Interventional

Funder types: Industry

Identifiers

NCT07123454

D9890C00001

Details and patient eligibility

About

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).

Full 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

Enrollment: 91 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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91 participants in 1 patient group

Module 1: AZD4512 Monotherapy dose escalation + backfill

Experimental group

Description:

In Mod 1, the efficacy and safety of AZD4512 will be evaluated in R/R B-NHL. Module 1 will consist of both dose escalation and Pharmacodynamic/safety backfills which may be used to support MTD and/or Optimal biological dose (OBD)

Treatment:

Drug: AZD4512