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

Phase 2RecruitingNCT06526793

AstraZeneca240 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

240

Conditions

B-cell Non-Hodgkin Lymphoma Follicular Lymphoma (FL)Large B-Cell Lymphoma (LBCL)

Interventions

SurovatamigDRUG

Investigational Product administered via intravenous infusion.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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 exclusion criteria details may apply.

Locations (94)

Outcomes

Primary Outcomes

Overall response rate (ORR) (central review)

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

Time frame: 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.

Secondary Outcomes

Incidence, nature and severity of Adverse Events (AEs), Serious AEs and AEs of Special Interest (AESI)

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.

Time frame: From time of Informed Consent to 90-day safety follow-up visit

Incidence and nature of study drug discontinuation, dose reduction, and dose delay due to Adverse Events (AEs)

Incidence and nature of study drug discontinuation, dose reduction, and dose delay due to AEs

Time frame: From the start of treatment up to 2 years in Module 1 and up to 1 year for Module 2

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.

Time frame: To be assessed up to approximately 5 years.

Complete response (CR) rate (central review)

Complete response (CR) based on Lugano 2014 Response criteria for non-Hodgkin lymphoma, as determined by central review.

Central Contacts

AstraZeneca Clinical Study Information Center

CONTACT

1-877-240-9479 information.center@astrazeneca.com

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.

Research Site

Phoenix, Arizona, United States

NOT_YET_RECRUITING

Research Site

Duarte, California, United States

RECRUITING

Research Site

Jacksonville, Florida, United States

NOT_YET_RECRUITING

Research Site

Tampa, Florida, United States

RECRUITING

Research Site

Chicago, Illinois, United States

NOT_YET_RECRUITING

Research Site

Iowa City, Iowa, United States

NOT_YET_RECRUITING

Research Site

Waukee, Iowa, United States

RECRUITING

Research Site

Overland Park, Kansas, United States

WITHDRAWN

Research Site

Rochester, Minnesota, United States

RECRUITING

Research Site

St Louis, Missouri, United States

WITHDRAWN

...and 84 more locations

Time frame: To be assessed up through study completion, up to approximately 5 years

Complete response (CR) rate (investigator assessment)

Complete response (CR) based on Lugano 2014 Response criteria of non-Hodgkin lymphoma, as determined by investigator assessment.

Time frame: To be assessed up through study completion, up to approximately 5 years

Overall response rate (ORR) (investigator assessment)

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.

Time frame: 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 complete response (DoCR)

Defined as the time from achievement of complete response (CR) to relapse or death due any cause, as assessed by central review

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: To be assessed up to approximately 5 years.

Plasma concentrations of surovatamig

To characterize the plasma concentration of surovatamig as monotherapy

Time frame: From Cycle 1 Day 1 (pre-dose) (each cycle is 28 days) up to 90 days after end of treatment

Area under the concentration time curve (AUC)

To characterize the pharmacokinetics (PK) AUC of surovatamig as monotherapy

Time frame: From Cycle 1 Day 1 (pre-dose) (each cycle is 28 days) up to 90 days after end of treatment

Maximum plasma concentration (Cmax)

To characterize the pharmacokinetics (PK) (Cmax) of surovatamig as monotherapy

Time frame: From Cycle 1 Day 1 (pre-dose) (each cycle is 28 days) up to 90 days after end of treatment

Time to maximum plasma concentration (Tmax)

To characterize the pharmacokinetics (PK) (Tmax) of surovatamig as monotherapy

Time frame: From Cycle 1 Day 1 (pre-dose) (each cycle is 28 days) up to 90 days after end of treatment

A trough concentration (Cthrough)

To characterize the pharmacokinetics (PK) (C through) of surovatamig as monotherapy

Time frame: From Cycle 1 Day 1 (pre-dose) (each cycle is 28 days) up to 90 days after end of treatment

Immunogenecity of surovatamig

The number and percentage of participants who develop Anti-Drug Antibodies (ADAs)

Time frame: 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)

Change from baseline in EORTC IL233 scales

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).

Time frame: 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 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"

Time frame: To be assessed up through study completion, up to approximately 5 years

Change from baseline in EORTC IL 232 QL2 scores

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.

Time frame: 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 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).

Time frame: To be assessed up through study completion, up to approximately 5 years

Minimal residual disease (MRD)

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.

Time frame: To be assessed up through study completion, up to approximately 5 years