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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT07123454




Registration number
NCT07123454
Ethics application status
Date submitted
24/07/2025
Date registered
14/08/2025
Date last updated
14/08/2025

Titles & IDs
Public title
A Phase I/II Study of AZD4512 Monotherapy or in Combination With Anticancer Agents in Participants With Relapsed/Refractory B-cell Non-Hodgkin Lymphoma
Scientific title
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)
Secondary ID [1] 0 0
D9890C00001
Universal Trial Number (UTN)
Trial acronym
Lumi-NHL
Linked study record

Health condition
Health condition(s) or problem(s) studied:
B-cell Non-Hodgkin Lymphoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - High grade lymphoma
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - Low grade lymphoma
Other 0 0 0 0
Research that is not of generic health relevance and not applicable to specific health categories listed above

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - AZD4512

Experimental: Module 1: AZD4512 Monotherapy dose escalation + backfill - 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: Drugs: AZD4512
AZD4512 is an antibody-drug conjugate targeting cluster of differentiation 22 (CD22) that will be administered via IV infusion
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Percentage of participants with dose-limiting toxicities (DLTs)
Timepoint [1] 0 0
Up to 4 weeks
Primary outcome [2] 0 0
Frequency, duration, severity of Treatment-Emergent Adverse Events (TEAEs) and Treatment-Related Adverse Events (TRAEs) and Serious Adverse Events (SAEs)
Timepoint [2] 0 0
From the first dose up to and including 30 (+7) days after the last dose of study treatment , but prior to subsequent cancer therapy
Primary outcome [3] 0 0
Frequency of SAEs/AEs leading to discontinuation of AZD4512
Timepoint [3] 0 0
From the first dose up to and including 30 (+7) days after the last dose of study treatment , but prior to subsequent cancer therapy
Primary outcome [4] 0 0
Number of participants with clinically significant alterations in vitals signs and abnormal laboratory parameters
Timepoint [4] 0 0
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 [1] 0 0
Objective response rate (ORR)
Timepoint [1] 0 0
Up to 2 years
Secondary outcome [2] 0 0
Complete response (CR) rate
Timepoint [2] 0 0
Up to 2 years
Secondary outcome [3] 0 0
Duration of response (DoR)
Timepoint [3] 0 0
Up to 2 years
Secondary outcome [4] 0 0
Progression-free survival (PFS)
Timepoint [4] 0 0
Up to 2 years
Secondary outcome [5] 0 0
Overall survival (OS)
Timepoint [5] 0 0
Up to 2 years
Secondary outcome [6] 0 0
Area Under plasma concentration-time Curve (AUC) of AZD4512, total antibody and total unconjugated warhead
Timepoint [6] 0 0
Up to 2 years
Secondary outcome [7] 0 0
Observed plasma (peak) drug concentration (Cmax) of AZD4512, total antibody and total unconjugated warhead
Timepoint [7] 0 0
Up to 2 years
Secondary outcome [8] 0 0
Trough concentration (Ctrough) of AZD4512, total antibody and total unconjugated warhead
Timepoint [8] 0 0
Up to 2 years
Secondary outcome [9] 0 0
Half life of AZD4512, total antibody and total unconjugated warhead
Timepoint [9] 0 0
Up to 2 years
Secondary outcome [10] 0 0
Time to reach peak or maximum observed concentration (tmax) of AZD4512, total antibody and total unconjugated warhead
Timepoint [10] 0 0
Up to 2 years
Secondary outcome [11] 0 0
Total clearance of AZD4512, total antibody and total unconjugated warhead
Timepoint [11] 0 0
Up to 2 years
Secondary outcome [12] 0 0
The number and percentage of participants who develop anti-drug antibodies (ADAs)
Timepoint [12] 0 0
Up to 2 years

Eligibility
Key inclusion criteria
Key

* 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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
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 design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
31/10/2025
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/03/2028
Actual
Sample size
Target
91
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Research Site - Melbourne
Recruitment postcode(s) [1] 0 0
3000 - Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Florida
Country [3] 0 0
United States of America
State/province [3] 0 0
Minnesota
Country [4] 0 0
United States of America
State/province [4] 0 0
New York
Country [5] 0 0
United States of America
State/province [5] 0 0
Ohio
Country [6] 0 0
United States of America
State/province [6] 0 0
Tennessee
Country [7] 0 0
Italy
State/province [7] 0 0
Bologna
Country [8] 0 0
Italy
State/province [8] 0 0
Milan
Country [9] 0 0
Japan
State/province [9] 0 0
Bunkyo City
Country [10] 0 0
Japan
State/province [10] 0 0
Kotoku
Country [11] 0 0
South Korea
State/province [11] 0 0
Seoul
Country [12] 0 0
Taiwan
State/province [12] 0 0
Taipei
Country [13] 0 0
United Kingdom
State/province [13] 0 0
London
Country [14] 0 0
United Kingdom
State/province [14] 0 0
Newcastle upon Tyne

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
AstraZeneca
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
AstraZeneca Clinical Study Information Center
Address 0 0
Country 0 0
Phone 0 0
1-877-240-9479
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal Vivli.org. All requests will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.

Supporting document/s available: Study protocol, Statistical analysis plan (SAP)
When will data be available (start and end dates)?
AstraZeneca will meet or exceed data availability as per the commitments made to the European Federation of Pharmaceutical Industries and Associations (EFPIA) and the Pharmaceutical Research and Manufacturers of America (PhRMA) Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
Available to whom?
When a request has been approved AstraZeneca will provide access to the anonymized individual patient-level data via secure research environment Vivli.org. Signed Data Usage Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information.
Available for what types of analyses?
How or where can data be obtained?
IPD available at link: https://vivli.org/


What supporting documents are/will be available?

No Supporting Document Provided


Results publications and other study-related documents

No documents have been uploaded by study researchers.

Results not provided in https://clinicaltrials.gov/study/NCT07123454