AZD0486 as Monotherapy in Participants With Relapsed/Refractory (R/R) B-cell NHL

Phase 2

Recruiting

• Conditions: B-cell Non-Hodgkin Lymphoma; Follicular Lymphoma (FL); Diffuse Large B-Cell Lymphoma (DLBCL)
• Interventions: Drug: AZD0486

• Registration Number: NCT06526793
• Lead Sponsor: AstraZeneca

Brief Summary

This is a Phase 2 global, multi-center, open-label study to assess the efficacy, safety and tolerability of AZD0486 monotherapy in adult participants with relapsed/refractory B-cell non-Hodgkin lymphoma (NHL) who have received at least two prior lines of therapies. The study has 2 Modules: Module 1 for FL and Module 2 for DLBCL.

Detailed Description

This is a modular, Phase II, multicenter, single-arm, open-label study to evaluate the efficacy and safety of AZD0486 monotherapy administered as an intravenous (IV) infusion in participants with relapsed or refractory B-NHL. The purpose of this study is to determine the efficacy and safety of AZD0486 administered at the RP2D in adults 18 to 80 years of age with relapsed or refractory B-NHL.

Study Timeline

• Study First Submitted: 2024-07-03
• Study First Submitted QC: 2024-07-24
• Study First Posted: 2024-07-30
• Study Start: 2024-11-27
• Status Verified: 2025-04
• Last Update Submitted: 2025-04-25
• Last Update Posted: 2025-04-27
• Primary Completion: 2027-03-10
• Study Completion: 2029-06-14

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 240

Inclusion Criteria

• Aged 18 to 80 years old

  • Histologically confirmed relapsed refractory FL (Module 1) and DLBCL (Module 2) after at least 2 prior lines of therapy

  • ECOG performance status 0 to 2

  • Locally confirmed CD-19 expression in lymphoma cells after progression from last CD 19 directed therapy

  • FDG-avid disease with at least one bi-dimensionally measurable nodal lesion (defined as > 1.5 cm in its longest dimension), or extranodal lesion (defined as > 1.0 cm in its longest dimension)

  • Adequate hematological function: ANC ≥ 1000/mm3, platelets

    • 75,000/mm3, hemoglobin ≥ 9 g/dL. Transfusion and/or growth factor are allowed but counts must be stable for at least 72 hours afterwards prior to screening

  • Adequate liver function: total bilirubin <1.5x ULN, AST/ALT ≤ 3xULN Note: Patients with documented history of Gilbert's Syndrome and in whom total bilirubin elevations are accompanied by elevated indirect bilirubin are eligible)

  • Adequate renal function: creatinine clearance (CrCl) of ≥ 45 mL/min

  The above is a summary, other inclusion criteria details may apply.

2. Key

Exclusion Criteria

• Diagnosis of CLL, Burkitt lymphoma, or Richter's transformation
  • Active CNS involvement by B-NHL
  • Leukemic presentation of B-NHL
  • History or presence of clinically relevant CNS pathology such as epilepsy, seizure, paresis, aphasia, stroke, severe brain injuries, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome, or psychosis
  • Prior therapy with T-cell engager (TCE) within 8 weeks, CAR T- cell therapy or autologous Hematopoietic Stem Cell Transplantation (HSCT) within 12 weeks, or prior allogeneic HSCT within 24 weeks of first dose of AZD0486
  • Requires chronic immunosuppressive therapy
  • Unresolved non hematological AEs ≥ Grade 2 from prior therapies; history of ≥ Grade 3 CRS or neurotoxicity from prior CAR-T or TCE therapy
  • History of major cardiac abnormalities.
  • If female, participant must not be pregnant or breastfeeding.

The above is a summary, other exclusion criteria details may apply.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Module 1: AZD0486 Monotherapy in Participants with Relapsed or Refractory Follicular Lymphoma	AZD0486	In Module 1, the efficacy and safety of AZD0486 at the RP2D will be evaluated in R/R FL. AZD0486 will be administered as intravenous infusion.
Module 2: AZD0486 Monotherapy in Participants with Relapsed or Refractory DLBCL	AZD0486	In Module 2, the efficacy and safety of AZD0486 at the RP2D will be evaluated in R/R DLBCL. AZD0486 will be administered as intravenous infusion.

Primary Outcome Measures

Name	Time	Method
Overall response rate (ORR)	Module 1: from first dose to end of treatment or data cutoff, whichever comes first, assessed up to about 24 months. Module 2: from first dose to end of treatment or data cutoff, whichever comes first, assessed up to about 12 months.	Overall response rate (ORR), defined as the proportion of participants achieving either a PR or CR based on Lugano 2014 response criteria for non-Hodgkin Lymphoma, as determined by central review

Secondary Outcome Measures

Name	Time	Method
Overall response rate (ORR)	Module 1: from first dose to end of treatment or data cutoff, whichever comes first, assessed up to about 24 months. Module 2: from first dose to end of treatment or data cutoff, whichever comes first, assessed up to about 12 months.	Overall response rate (ORR), defined as the proportion of participants achieving either a PR or CR based on Lugano 2014 Response criteria of non-Hodgkin lymphoma, as determined by investigator assessment.
Duration of response (DoR)	To be assessed up to approximately 5 years.	Defined as the time from the date of first documented response until date of documented progression by Lugano 2014 response criteria as determined by central review or death due to any cause.
Complete response (CR) rate	To be assessed up through study completion, up to approximately 5 years	Complete response (CR) based on Lugano 2014 Response criteria of non-Hodgkin lymphoma, as determined by investigator assessment.
Change from baseline in IL232 QL2 score	To be assessed up through study completion, up to approximately 5 years	To evaluate patient-reported impact of disease general quality of life and functioning, while on AZD0486.; EORTC IL232 - European Organisation for Research and Treatment of Cancer IL232- this questionnaire is assessing Patient-reported Severity of Treatment-and Disease-related Function and Quality of Life. This is a 15-item questionnaire, and item 1-13 are rated on a 4-point scale ranging from 1 (not at all) to 4 (very much), item 14-15 are rated on a 7-point scale ranging from 1 (very poor) to 7 (excellent).
Change from baseline in PGI-T scale	To be assessed up through study completion, up to approximately 5 years	To evaluate patient-reported tolerability of AZD0486, overall side-effect burden.; PGI-T scale - Patient Global Impression of Treatment Tolerability is a 1 item questionnaire rated on a 7-point scale ranging from "not at all" to "very much"
Duration of CR (DoCR)	To be assessed up to approximately 5 years.	Defined as the time from achievement of CR to relapse or death due any cause, as assessed by central review
Time to response (TTR)	From the first dose until the first objective response, up to approximately 5 years.	Defined as the time from first dose until first documented objective response, as assessed by central review.
Progression-free survival (PFS)	To be assessed up to approximately 5 years.	Defined as the time from the date of first dose until documented disease progression based on Lugano 2014 Response Criteria, or death due to any cause.
Time to next anti-lymphoma (TTNT)	To be assessed up to approximately 5 years.	Defined as time from first dose until the start of subsequent anti-lymphoma therapy.
Overall survival (OS)	To be assessed up to approximately 5 years.	Defined as the time from first dose until the date of death due to any cause.
Event-free survival (EFS)	To be assessed up to approximately 5 years	Defined as the time from first dose until disease progression, relapse, or initiation of subsequent systemic anti-lymphoma treatment, or death due to any cause, as assessed by central review.
Minimal residual disease (MRD)	To be assessed up through study completion, up to approximately 5 years	MRD-negative CR rate, defined as the proportion of participants who achieved MRD-negativity in plasma by NGS while in CR per the Lugano Response criteria for non-Hogkin lymphoma as determined by central review.
Change from baseline in EORTC IL233 scales	To be assessed up through study completion, up to approximately 5 years	To evaluate patient-reported tolerability of AZD0486, including severity of key treatment-related symptoms and overall side-effect burden; EORCT IL233 scales - European Organisation for Research and Treatment of Cancer Il233 scales- this questionnaire is assessing Patient-reported Severity of Treatment-and Disease-related Symptoms, it is a 15-item questionnaire, and each item is rated on a 4-point scale ranging from 1 (not at all) to 4 (very much).
Change from baseline in FACT-LymS scales	To be assessed up through study completion, up to approximately 5 years	To evaluate patient-reported severity of key disease-related symptoms, as well as the impact of disease on lymphoma-specific concerns, while on AZD0486; Functional Assessment of Cancer Therapy - Lymphoma (FACT-Lym) FACT-LymS - Lymphoma-specific Subscale from the FACT-Lym Questionnaire is a 15-item questionnaire, and each item is rated on a 5-point scale ranging from 0 (not at all) to 4 (very much).

Trial Locations

Locations (1)

Research Site; 🇬🇧 Plymouth, United Kingdom