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

PHASE2NOT_YET_RECRUITING

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.

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Study details:

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.

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Eligibility criteria

Researchers look for people who fit a certain description, called eligibility criteria. See if you qualify.

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

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.

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Eligibility

Age eligible for study : 18 and older

Healthy volunteers accepted : No

Gender eligible for study: All

Things to know

Study dates

Study start: 2024-10-28

Primary completion: 2027-02-08

Study completion finish: 2029-05-15

Study type

TREATMENT

Phase

PHASE2

Trial ID

NCT06526793

Intervention or treatment

DRUG: AZD0486

Conditions

• B-cell Non-Hodgkin Lymphoma
• Follicular Lymphoma (FL)
• Diffuse Large B-Cell Lymphoma (DLBCL)

Image related to B-cell Non-Hodgkin Lymphoma

Condition: B-cell Non-Hodgkin Lymphoma, Follicular Lymphoma (FL) and more
DRUG: AZD0486
Heidelberg, Not Specified, Australia and more
Sponsor: AstraZeneca

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Find a site

Closest Location:

Research Site

Research sites nearby

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Research Site
Heidelberg, Not Specified, Australia
Research Site
Macquarie University, Not Specified, Australia
Research Site
Nedlands, Not Specified, Australia

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: AZD0486 Monotherapy in Participants with Relapsed or Refractory Follicular Lymphoma 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.	DRUG: AZD0486 Investigational Product administered via intravenous infusion.
EXPERIMENTAL: Module 2: AZD0486 Monotherapy in Participants with Relapsed or Refractory DLBCL 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.	DRUG: AZD0486 Investigational Product administered via intravenous infusion.

What is the study measuring?

Primary outcome

Primary Outcome Measure	Primary Outcome Description	Primary Outcome Time Frame
Overall response rate (ORR)	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	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.

Secondary outcome

Secondary Outcome Measure	Secondary Outcome Description	Secondary Outcome Time Frame
Duration of response (DoR)	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.	To be assessed up to approximately 5 years.
Complete response (CR) rate	Complete response (CR) based on Lugano 2014 Response criteria for non-Hodgkin lymphoma, as determined by central review.	To be assessed up through study completion, up to approximately 5 years
Complete response (CR) rate	Complete response (CR) based on Lugano 2014 Response criteria of non-Hodgkin lymphoma, as determined by investigator assessment.	To be assessed up through study completion, up to approximately 5 years
Overall response rate (ORR)	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.	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.
Duration of CR (DoCR)	Defined as the time from achievement of CR to relapse or death due any cause, as assessed by central review	To be assessed up to approximately 5 years.
Time to response (TTR)	Defined as the time from first dose until first documented objective response, as assessed by central review.	From the first dose until the first objective response, up to approximately 5 years.
Event-free survival (EFS)	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.	To be assessed up to approximately 5 years
Progression-free survival (PFS)	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.	To be assessed up to approximately 5 years.
Time to next anti-lymphoma (TTNT)	Defined as time from first dose until the start of subsequent anti-lymphoma therapy.	To be assessed up to approximately 5 years.
Overall survival (OS)	Defined as the time from first dose until the date of death due to any cause.	To be assessed up to approximately 5 years.
Minimal residual disease (MRD)	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.	To be assessed up through study completion, up to approximately 5 years
Change from baseline in EORTC IL233 scales	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).	To be assessed up through study completion, up to approximately 5 years
Change from baseline in IL232 QL2 score	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).	To be assessed up through study completion, up to approximately 5 years
Change from baseline in FACT-LymS scales	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).	To be assessed up through study completion, up to approximately 5 years
Change from baseline in PGI-T scale	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"	To be assessed up through study completion, up to approximately 5 years

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References

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