A Phase I/II Study of AZD4512 Monotherapy or in Combination With Anticancer Agents in Participants With Relapsed/Refractory B-cell Non-Hodgkin Lymphoma
PHASE1PHASE2RECRUITING
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).
Study details:
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
Researchers look for people who fit a certain description, called eligibility criteria. See if you qualify.
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.
- 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).
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.
Eligibility
Age eligible for study : NA
Healthy volunteers accepted : No
Gender eligible for study: ALL
Things to know
Study dates
Study start:
Primary completion:
Study completion finish:
Study type
TREATMENT
Phase
- PHASE1PHASE2
Study ID
NCT07123454
Intervention or treatment
DRUG: AZD4512
Conditions
- B-cell Non-Hodgkin Lymphoma
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Research sites nearby
Closest Location:
Research Site
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Research Site
Melbourne, Australia
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Who is running the clinical trial?
A
AstraZeneca
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
| Participant Group/Arm | Intervention/Treatment |
|---|---|
EXPERIMENTAL: Module 1: AZD4512 Monotherapy dose escalation + backfill
| Drug: AZD4512 |
What is the study measuring?
Primary Outcome
| Measure | Description | Time Frame |
|---|---|---|
| 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 | 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 | 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 | 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 | 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 Outcome
| Measure | Description | Time Frame |
|---|---|---|
| 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. | Up to 2 years |
| 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. | Up to 2 years |
| 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. | Up to 2 years |
| 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. | Up to 2 years |
| Overall survival (OS) | OS, defined as the time from the date of first dose until date of death, to evaluate the preliminary efficacy of AZD4512 monotherapy in participants with R/R B-NHL. | Up to 2 years |
| Area Under plasma concentration-time Curve (AUC) of AZD4512, total antibody and total unconjugated warhead | To characterize the AUC of AZD4512 as monotherapy in participants with R/R B-NHL | Up to 2 years |
| Observed plasma (peak) drug concentration (Cmax) of AZD4512, total antibody and total unconjugated warhead | To characterize the Cmax of AZD4512 as monotherapy in participants with R/R B-NHL | Up to 2 years |
| Trough concentration (Ctrough) of AZD4512, total antibody and total unconjugated warhead | To characterize the Ctrough of AZD4512 as monotherapy in participants with R/R B-NHL | Up to 2 years |
| Half life of AZD4512, total antibody and total unconjugated warhead | To characterize the Half life of AZD4512 as monotherapy in participants with R/R B-NHL | Up to 2 years |
| Time to reach peak or maximum observed concentration (tmax) of AZD4512, total antibody and total unconjugated warhead | To characterize the Tmax of AZD4512 as monotherapy in participants with R/R B-NHL | Up to 2 years |
| Total clearance of AZD4512, total antibody and total unconjugated warhead | To characterize the Total clearance of AZD4512 as monotherapy in participants with R/R B-NHL | Up to 2 years |
| The number and percentage of participants who develop anti-drug antibodies (ADAs) | To determine the immunogenicity of AZD4512 as monotherapy in participants with R/R B-NHL | Up to 2 years |
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References
Clinical Trials Gov: A Phase I/II Study of AZD4512 Monotherapy or in Combination With Anticancer Agents in Participants With Relapsed/Refractory B-cell Non-Hodgkin LymphomaOther trials to consider
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