A trial to learn how safe AZD4512 is with and without other cancer drugs and how it works in the bodies of people with B-cell non-Hodgkin lymphoma (B-NHL)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

AstraZeneca AB

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Hemic and Lymphatic Diseases [C15]

Trial duration

19 Dec 2025 → ongoing

Decision date (initial)

2025-11-18

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Dose response, Pharmacodynamic, Safety, Pharmacokinetic

To assess the safety and tolerability of AZD4512 monotherapy in participants with R/R B-NHL and establish the MTD and/or OBD

Secondary objectives 3

1. To evaluate the preliminary efficacy of AZD4512 monotherapy in participants with R/R B-NHL
2. To characterize the PK of AZD4512 as monotherapy in participants with R/R B-NHL
3. To determine the immunogenicity of AZD4512 as monotherapy in participants with R/R B-NHL

Conditions and MedDRA coding

Non-Hodgkin lymphoma (NHL)

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. 1. Age. Participants must be 18 years of age or older and capable of understanding and complying with parameters as outlined in the protocol and able to sign informed consent.
2. 2. mesurable disease: FDG-PET-avid lymphomas: Must have at least one measurable FDG-PET-avid lesion, based on bi-dimensional assessment on PET and CT/MRI scan, defined as at least one nodal lesion > 1.5 cm in the long axis or at least one extra-nodal lesion > 1 cm in the long axis. FDG non-avid lymphomas: Must have at least one measurable based on bi-dimensional assessment on CT/MRI scan, defined as at least one nodal lesion > 1.5 cm in the long axis or at least one extra-nodal lesion > 1 cm in the long axis.
3. 3. ECOG Performance Status of ≤ 2.
4. 4. Life expectancy ≥ 12 weeks.
5. 5.Adequate organ and Bone Marrow function
6. 6. Contraceptive use by participants or participant partners should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
7. 7. Capable of giving signed informed consent and able to participate in all required study visits, evaluations, treatment plan, and other study procedures.

Exclusion criteria 12

1. 1.Active CNS involvement by lymphoma, leptomeningeal disease, or spinal cord compression. Participants with a prior history of CNS localization of lymphoma who received treatment are eligible provided that there is no evidence of CNS involvement at study entry as documented by CSF cytology and/or brain MRI.
2. 2. Unresolved non-hematological AEs ≥ Grade 2 NCI CTCAE V5.0 from prior anticancer therapy, except for: (a) Alopecia, Fatigue, Grade 2 Peripheral neuropathy (peripheral neuropathy ≥ Grade 3 will be excluded), Endocrine disorders that are controlled with replacement therapy, or Stable vitiligo.
3. 3.Any severe and uncontrolled medical condition (eg, diabetes mellitus, any history of seizure, bleeding diathesis, hepatic failure, clinically significant liver disease including cirrhosis or hepatitis, unstable respiratory or cardiac conditions, active infection [bacterial, viral, fungal, or other infection]), any major infection that required hospitalization or treatment with IV or oral antimicrobials within 14 days of Day 1.
4. 4.Other malignancy within 2 years prior to screening with the exception of: a) Malignancy treated with curative intent and with no evidence of active disease present for more than 2 years before screening and considered to be at low risk of recurrence by the treating physician. b) Adequately treated lentigo maligna melanoma without current evidence of disease or adequately controlled non-melanomatous skin cancer. c) Adequately treated carcinoma in situ without evidence of disease.
5. 5.History of non-infectious ILD/pneumonitis that has required oral or IV steroids or supplemental oxygen, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening.
6. 6.Serological status reflecting active HBV or HCV infections
7. 7.Active HIV infection. HIV-infected participants on effective anti-retroviral therapy with sustained undetectable viral load for longer than 6 months prior to enrollment are eligible for this study after confirmation from the sponsor.
8. 8.Cardiovascular disorder
9. 9. Participant has any medical or psychiatric condition which, in the opinion of the investigator or medical monitor, places the participant at an unacceptably high risk for toxicities, could interfere with successful or safe delivery of therapy, or could interfere with evaluation of the investigational product or interpretation of participant safety or study results. Examples include major psychiatric illness and drug or alcohol abuse.
10. 10.Prior/Concomitant Therapy - Received adoptive cellular therapy such as autologous or donor NK cell or T lymphocyte infusions [eg CAR-T cells]), or T-cell engager therapy, within 90 days prior to the first dose of study treatment. - Received any investigational drug chemotherapy, immunotherapy, immunosuppressant medication, medications or herbal supplements known to be strong inhibitors of CYP3A4 within 21 days (or 5 half-lives, whichever is shorter) prior to the first dose of study treatment. - Received radiation therapy with curative intent within 14 days prior to the first dose of study treatment. Localized palliative radiotherapy is permitted. - Received prior allogeneic HSCT, unless the transplant occurred > 180 days prior to the first scheduled dose and the participant has no active graft-versus-host disease requiring treatment and has been stable off immunosuppression for at least 2 months or received prior autologous HSCT unless the transplant occurred > 90 days prior to the first dose of study treatment and transplant-related toxicities are resolved to at least a Grade 1. - Received major surgery within 28 days prior to the first dose of study treatment. - Any concomitant medications known to prolong QTc and/or have a known risk for Torsades de Pointes within 21 days or 5 half-lives, whichever is longer prior to the first dose of AZD4512 through the end of DLT review period.
11. 11. Previous dosing with AZD4512 in the present study or participants with a known hypersensitivity to AZD4512 or any of the excipients of the product.
12. 12. For women-only – currently pregnant (confirmed with positive pregnancy test) or breast-feeding (including when breast-feeding is interrupted) or intend to become pregnant during the study period.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 4

1. Percentage of participants with DLT during the DLT period
2. Frequency, duration, severity of TEAEs and TRAEs and SAEs
3. SAEs/AEs leading to discontinuation of AZD4512
4. Clinically significant alterations in vital signs and abnormal laboratory parameters

Secondary endpoints 5

1. Response assessment according to Lugano classification (Cheson et al 2014) for malignant lymphoma: ORR, CR rate, DoR and PFS
2. Overall survival
3. Plasma concentrations of AZD4512, total antibody and total unconjugated warhead
4. Plasma PK parameters of AZD4512, total antibody and total unconjugated warhead but not limited to AUC, Cmax, tmax, Ctrough t1/2, and clearance as data allow
5. The number and percentage of participants who develop ADAs

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

AstraZeneca AB

Sponsor organisation

AstraZeneca AB

Address

-

City

Sodertalje

Postcode

151 85

Country

Sweden

Scientific contact point

Organisation

AstraZeneca AB

Contact name

AstraZeneca Clinical Study Information Center

Public contact point

Organisation

AstraZeneca AB

Contact name

AstraZeneca Clinical Study Information Center

Locations

1 EU/EEA country · 3 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 9 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications