Recruiting
Phase 1/2
A Phase I/II Study of AZD4512 Monotherapy or in Combination With Anticancer Agents in Participants With Relapsed/Refractory B-cell Non-Hodgkin Lymphoma
Condition(s) studied
B-cell Non-Hodgkin Lymphoma
Investigational drug(s) / intervention(s)
AZD4512: AZD4512 is an antibody-drug conjugate targeting cluster of differentiation 22 (CD22) that will be administered via IV infusion
Surovatamig: Surovatamig (AZD0486) is a 'bispecific' antibody to be administered via IV infusion
Study 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).
Eligibility
Core Inclusion Criteria
* Eligible patients must be adults (≥18 years)
* Additional criteria include measurable disease by Lugano 2014, 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).
Module 1 Monotherapy Inclusion criteria
* Documented histologically confirmed diagnosis of B-cell non-Hodgkin lymphoma (B-NHL) as per World Health Organization (WHO) 2022 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), high-grade B-cell lymphoma (HGBCL) NOS, DLBCL/HGBCL with MYC and BCL2 rearrangements, primary mediastinal Large B-cell lymphoma, T-cell/histiocyte-rich LBCL, and transformed indolent lymphoma) and mantle cell lymphoma.
* Patients with LBCL must have relapsed or refractory disease after at least two prior lines of systemic therapy and lack additional standard options with established benefit. Additionally 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 Participants with MCL must have previously received an anti-CD20 based therapy, and BTKi
Module 2 Surovatamig Combination Inclusion criteria
* Documented histologically confirmed diagnosis of LBCL as defined as: DLBCL ( not otherwise specified), Grade 3b FL, DLBCL/high grade B-cell lymphoma with MYC and BCL2 rearrangements, High grade B-cell lymphoma (not other specified), Primary mediastinal LBCL, T-cell/histiocyte-rich LBCL, Transformations of indolent B-cell lymphoma.
* Participants who have received previous CD19-directed therapy must have locally assessed confirmation (after completion of the CD19-directed therapy) to demonstrate presence of CD19 expression by immunohistochemistry or flow cytometry.
* Patients must have relapsed or refractory disease after at least two prior lines of systemic therapy and lack additional standard options with established benefit. Additionally 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
Core Exclusion Criteria
* Active CNS involvement from their B-NHL. Exclusion also applies to those who have received CAR-T , within 6 months or T cell engager therapies within 90 days prior to C1D1, any investigational drug or other systemic anticancer therapies (except low-dose corticosteroids, ≤10mg prednisone/day) within 21 days or 5 half-lives, and curative radiation within 14 days (localized palliative radiotherapy is allowed).
* Other exclusions include: allogeneic HSCT within 180 days (unless stable without active GVHD for ≥2 months), autologous HSCT within 90 days (unless resolved toxicities), major surgery within 28 days, use of strong CYP3A inhibitors within 14 days or 5 half-lives before the dosing date, use of QTc-prolonging agents within 5 half-lives before the dosing date, 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 ILD/pneumonitis are also excluded.
* Females who are pregnant or breastfeeding are not eligible.
* Previous dosing with AZD4512
Module 1 Exclusion Criteria Patients are excluded if they have a diagnosis of post transplant lymphoproliferative disease, Richter's transformation, Burkitt's lymphoma, CLL/SLL, Waldenstrom Macroglobulinemia/ Lymphoplasmacytic Lymphoma
Module 2 Exclusion Criteria
Participants will be excluded if they have:
* Clinically significant central nervous system (CNS) pathologies, including neurological, neurodegenerative, psychiatric, or other severe mental health conditions.
* Active or prior CNS involvement related to autoimmune disease.
* Leukemic presentation of non-Hodgkin lymphoma (NHL), with circulating malignant lymphoid cells in peripheral blood.
* A history of hemophagocytic lymphohistiocytosis/macrophage activation syndrome (HLH/MAS). • Prior Grade ≥3 cytokine release syndrome (CRS) or immune effector cell-associated neurotoxicity syndrome (ICANS) following CAR T-cell or T-cell engager (TCE) therapy, or any unresolved CRS/ICANS.
* Prior exposure to surovatamig.
* Diagnosis of Richter's transformation
Primary outcome measure(s)
- Percentage of participants with dose-limiting toxicities (DLTs) during the DLT period — Up to 4 weeks
To assess the safety and tolerability of AZD4512 monotherapy or in combination in participants with R/R B-NHL
- Frequency, duration, severity of Treatment-Emergent Adverse Events (TEAEs) and Treatment-Related Adverse Events (TRAEs) and Serious Adverse Events (SAEs) — From the first dose up to and including 30 (+7) days after the last dose of study treatment , but prior to subsequent cancer therapy
To assess the safety and tolerability of AZD4512 monotherapy or in combination in participants with R/R B-NHL
- Frequency of SAEs/AEs leading to discontinuation of study treatment — From the first dose up to and including 30 (+7) days after the last dose of study treatment , but prior to subsequent cancer therapy
To assess the safety and tolerability of AZD4512 monotherapy or in combination in participants with R/R B-NHL
- Number of participants with clinically significant alterations in vitals signs and abnormal laboratory parameters — From the first dose up to and including 30 (+7) days after the last dose of study treatment , but prior to subsequent cancer therapy
To assess the safety and tolerability of AZD4512 monotherapy or in combination in participants with R/R B-NHL
Trial sites (23)
| Facility | City | Region | Status |
| Research Site |
Irvine |
California |
Suspended |
| Research Site |
Jacksonville |
Florida |
Recruiting |
| Research Site |
Rochester |
Minnesota |
Recruiting |
| Research Site |
New York |
New York |
Suspended |
| Research Site |
New York |
New York |
Recruiting |
| Research Site |
Cleveland |
Ohio |
Withdrawn |
| Research Site |
Myrtle Beach |
South Carolina |
Withdrawn |
| Research Site |
Franklin |
Tennessee |
Recruiting |
| Research Site |
Macquarie University |
Australia |
Not Yet Recruiting |
| Research Site |
Melbourne |
Australia |
Recruiting |
| Research Site |
Chengdu |
China |
Not Yet Recruiting |
| Research Site |
Guangzhou |
China |
Not Yet Recruiting |
| Research Site |
Bologna |
Italy |
Recruiting |
| Research Site |
Milan |
Italy |
Recruiting |
| Research Site |
Milan |
Italy |
Recruiting |
| Research Site |
Bunkyō City |
Japan |
Recruiting |
| Research Site |
Kōtoku |
Japan |
Recruiting |
| Research Site |
Seoul |
South Korea |
Recruiting |
| Research Site |
Seoul |
South Korea |
Recruiting |
| Research Site |
Taichung |
Taiwan |
Recruiting |
| Research Site |
Taipei |
Taiwan |
Recruiting |
| Research Site |
London |
United Kingdom |
Recruiting |
| Research Site |
Newcastle upon Tyne |
United Kingdom |
Recruiting |
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