B-cell Non-Hodgkin Lymphoma, Follicular Lymphoma (FL), Large B-Cell Lymphoma (LBCL)
Conditions
Keywords
AZD0486, Surovatamig, Follicular Lymphoma (FL), Large B-Cell Lymphoma (LBCL), Non-Hodgkin lymphoma (NHL), Relapsed/Refractory
Brief summary
This is a Phase 2 global, multi-center, open-label study to assess the efficacy, safety and tolerability of Surovatamig (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 LBCL.
Detailed description
This is a modular, Phase II, multicenter, single-arm, open-label study to evaluate the efficacy and safety of Surovatamig (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 years of age or older with relapsed or refractory B-NHL.
Interventions
DRUGSurovatamig
Investigational Product administered via intravenous infusion.
Sponsors
AstraZeneca
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
The trial will assess surovatamig (AZD0486) monotherapy given by IV infusion. Module 1 will evaluate the efficacy and safety of surovatamig monotherapy at the recommended Phase 2 dose (RP2D), in participants 18 years of age or older , with relapsed or refractory (R/R) follicular lymphoma (FL) who have received ≥ 2 prior therapies. Module 2 will evaluate the efficacy and safety of surovatamig monotherapy at the RP2D for participants 18 years of age or older with (R/R) large B-cell lymphoma (LBCL) who have received ≥ 2 prior therapies.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Key Inclusion Criteria: * Aged 18 years old and above * Histologically confirmed relapsed refractory FL (Module 1) and LBCL (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 or \< 5 × ULN in the presence of lymphoma involvement of the liver * Adequate renal function: creatinine clearance (CrCl) of ≥ 45 mL/min * Adequate cardiac function, defined as left ventricular ejection fraction (LVEF) ≥ 45% by echocardiogram or MUGA 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, neurodegenerative disorder including Parkinson's disease, cerebellar disease, organic brain syndrome, or psychosis or other severe mental illness * Prior therapy with T-cell engager (TCE) within 8 weeks, autologous Hematopoietic Stem Cell Transplantation (HSCT) within 12 weeks, CAR T- cell therapy within 6 months, or prior allogeneic HSCT within 24 weeks of first dose of surovatamig * 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall response rate (ORR) (central review) | Module 1: from first dose to end of treatment or data cutoff, whichever comes first, assessed up to approximately 24 months. Module 2: from first dose to end of treatment or data cutoff, whichever comes first, assessed up to approximately 12 months. | Overall response rate (ORR), defined as the proportion of participants achieving either a Partial Response (PR) or Complete Response (CR) based on Lugano 2014 response criteria for non-Hodgkin Lymphoma, as determined by central review |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Incidence, nature and severity of Adverse Events (AEs), Serious AEs and AEs of Special Interest (AESI) | From time of Informed Consent to 90-day safety follow-up visit | Incidence, nature, and severity of AEs/SAEs (based on NCI CTCAE v5.0/ASTCT criteria/Cairo-Bishop criteria with Howard modification) and changes in laboratory data, vital signs, and electrocardiograms (ECGs) compared with baseline. Incidence and severity of AESIs. |
| Incidence and nature of study drug discontinuation, dose reduction, and dose delay due to Adverse Events (AEs) | From the start of treatment up to 2 years in Module 1 and up to 1 year for Module 2 | Incidence and nature of study drug discontinuation, dose reduction, and dose delay due to AEs |
| 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 (central review) | To be assessed up through study completion, up to approximately 5 years | Complete response (CR) based on Lugano 2014 Response criteria for non-Hodgkin lymphoma, as determined by central review. |
| Complete response (CR) rate (investigator assessment) | 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. |
| Overall response rate (ORR) (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. | Overall response rate (ORR), defined as the proportion of participants achieving either a partial response (PR) or complete response (CR) based on Lugano 2014 Response criteria of non-Hodgkin lymphoma, as determined by investigator assessment. |
| Duration of complete response (DoCR) | To be assessed up to approximately 5 years. | Defined as the time from achievement of complete response (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. |
| 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. |
| 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. |
| Plasma concentrations of surovatamig | From Cycle 1 Day 1 (pre-dose) (each cycle is 28 days) up to 90 days after end of treatment | To characterize the plasma concentration of surovatamig as monotherapy |
| Area under the concentration time curve (AUC) | From Cycle 1 Day 1 (pre-dose) (each cycle is 28 days) up to 90 days after end of treatment | To characterize the pharmacokinetics (PK) AUC of surovatamig as monotherapy |
| Maximum plasma concentration (Cmax) | From Cycle 1 Day 1 (pre-dose) (each cycle is 28 days) up to 90 days after end of treatment | To characterize the pharmacokinetics (PK) (Cmax) of surovatamig as monotherapy |
| Time to maximum plasma concentration (Tmax) | From Cycle 1 Day 1 (pre-dose) (each cycle is 28 days) up to 90 days after end of treatment | To characterize the pharmacokinetics (PK) (Tmax) of surovatamig as monotherapy |
| A trough concentration (Cthrough) | From Cycle 1 Day 1 (pre-dose) (each cycle is 28 days) up to 90 days after end of treatment | To characterize the pharmacokinetics (PK) (C through) of surovatamig as monotherapy |
| Immunogenecity of surovatamig | From the first dose of study intervention, at predefined intervals throughout the administration of surovatamig (2 years in Module 1 and 1 year in Module 2) | The number and percentage of participants who develop Anti-Drug Antibodies (ADAs) |
| 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 surovatamig, 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 PGI-T scale | To be assessed up through study completion, up to approximately 5 years | To evaluate patient-reported tolerability of surovatamig, 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" |
| Change from baseline in EORTC IL 232 QL2 scores | 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 surovatamig. European Organization for Research and Treatment of Cancer (EORTC) IL 232 will be used to evaluate impacts on function and HRQoL due to treatment and disease, which includes 13 EORTC QLQ-C30 function items assessing physical, social, role, and emotional function, as well as the EORTC QLQ-C30's 2 global health/HRQoL items. |
| 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 surovatamig 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). |
| Minimal residual disease (MRD) | To be assessed up through study completion, up to approximately 5 years | MRD-negative complete response (CR) rate, defined as the proportion of participants who achieved MRD-negativity in plasma by next generation sequencing (NGS) while in complete response (CR) per the Lugano Response criteria for non-Hodgkin lymphoma as determined by central review. |
Countries
Australia, Brazil, Canada, China, Denmark, France, Germany, Hong Kong, Italy, Japan, South Korea, Spain, Sweden, Taiwan, United Kingdom, United States
Contacts
CONTACTAstraZeneca Clinical Study Information Center
Outcome results
None listed