AZD0486 as Monotherapy in Participants With Relapsed/Refractory (R/R) B-cell NHL
NCT Number: NCT06526793
Status: NOT_YET_RECRUITING
Study Type: INTERVENTIONAL
Phases: PHASE2
Conditions: B-cell Non-Hodgkin Lymphoma|Follicular Lymphoma (FL)|Diffuse Large B-Cell Lymphoma (DLBCL)
Interventions: DRUG: AZD0486
Sponsor: AstraZeneca
Sex: ALL
Age: ADULT, OLDER_ADULT
Enrollment: 240
Study Design: Allocation: NON_RANDOMIZED|Intervention Model: SEQUENTIAL|Masking: NONE|Primary Purpose: TREATMENT
Start Date: 2024-10-28
Completion Date: 2029-05-15
Locations: Research Site, Duarte, California, 91010, United States|Research Site, Tampa, Florida, 33612, United States|Research Site, Des Moines, Iowa, 50314, United States|Research Site, Overland Park, Kansas, 66204, United States|Research Site, Rochester, Minnesota, 55905, United States|Research Site, Saint Louis, Missouri, 63110, United States|Research Site, New Brunswick, New Jersey, 08901, United States|Research Site, New York, New York, 10016, United States|Research Site, Charlotte, North Carolina, 28203, United States|Research Site, Columbus, Ohio, 43210, United States|Research Site, Portland, Oregon, 97239, United States|Research Site, Philadelphia, Pennsylvania, 19104, United States|Research Site, Pittsburgh, Pennsylvania, 15215, United States|Research Site, Houston, Texas, 77030, United States|Research Site, Milwaukee, Wisconsin, 53226, United States|Research Site, Heidelberg, 3084, Australia|Research Site, Kogarah, NSW 2217, Australia|Research Site, Macquarie University, 2109, Australia|Research Site, Nedlands, 6009, Australia|Research Site, Ottawa, Ontario, K1H 8L6, Canada|Research Site, Toronto, Ontario, M5G 2M9, Canada|Research Site, Berlin, 10967, Germany|Research Site, Chemnitz, 09116, Germany|Research Site, Essen, 45122, Germany|Research Site, Wuerzburg, 97080, Germany|Research Site, Chiba-shi, 260-8717, Japan|Research Site, Kashiwa, 277-8577, Japan|Research Site, Koto-ku, 135-8550, Japan|Research Site, Kumamoto-shi, 860-0008, Japan|Research Site, Niigata-shi, 951-8520, Japan|Research Site, Okayama-shi, 700-8558, Japan|Research Site, Osaka-shi, 541-8567, Japan|Research Site, Yokohama-shi, 241-8515, Japan|Research Site, Barcelona, 8035, Spain|Research Site, Madrid, 28040, Spain|Research Site, Pozuelo de Alarcon, 28223, Spain|Research Site, Kaohsiung City, 833401, Taiwan|Research Site, Kaohsiung, 80756, Taiwan|Research Site, Taichung, 404, Taiwan|Research Site, Taichung, 40705, Taiwan|Research Site, Tainan City, 70403, Taiwan|Research Site, Taipei City, 106, Taiwan

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.

Primary Outcome Measures: 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 Measures: 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