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

Official title

A Modular Phase 2, Single-arm, Multicenter, Open-label Study to Evaluate the Efficacy and Safety of Surovatamig (AZD0486) in Participants With Relapsed or Refractory (R/R) B-cell Non-Hodgkin Lymphoma (SOUNDTRACK-B)

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.

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 surovatamig (AZD0486) administered at the RP2D in adults 18 years of age or older with relapsed or refractory B-NHL.

Interventions

• Drug Surovatamig
  Investigational Product administered via intravenous infusion.

Primary outcome measures

• Overall response rate (ORR) (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 outcome measures (12)

• Incidence, nature and severity of Adverse Events (AEs), Serious AEs and AEs of Special Interest (AESI) [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) [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) [Time frame: To be assessed up to approximately 5 years.]
• Complete response (CR) rate (central review) [Time frame: To be assessed up through study completion, up to approximately 5 years]
• Complete response (CR) rate (investigator assessment) [Time frame: To be assessed up through study completion, up to approximately 5 years]
• Overall response rate (ORR) (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) [Time frame: To be assessed up to approximately 5 years.]
• Time to response (TTR) [Time frame: From the first dose until the first objective response, up to approximately 5 years.]
• Event-free survival (EFS) [Time frame: To be assessed up to approximately 5 years]
• Progression-free survival (PFS) [Time frame: To be assessed up to approximately 5 years.]
• Time to next anti-lymphoma (TTNT) [Time frame: To be assessed up to approximately 5 years.]
• Overall survival (OS) [Time frame: To be assessed up to approximately 5 years.]

Eligibility criteria

• 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.

• Key Exclusion Criteria:

• Diagnosis of CLL, Burkitt lymphoma, or Richter's transformation
• Active CNS involvement by B-NHL
• Leukemic presentation of B-NHL
• History of a clinically relevant CNS medical condition or pathology that required treatment in the preceding year, is currently symptomatic, or that the treating investigator considers to have the potential to interfere with the evaluation of safety, such as epilepsy, seizure, paresis, aphasia, stroke, severe brain injuries, dementia, neurodegenerative disorder including Parkinson's disease, cerebellar disease, organic brain syndrome, 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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Sequential

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 23 centers

• Research Site — Phoenix
• Research Site — Duarte
• Research Site — Jacksonville
• Research Site — Tampa
• Research Site — Chicago
• Research Site — Iowa City
• Research Site — Waukee
• Research Site — Overland Park
• … and 15 more centers

China · 11 centers

• Research Site — Chengdu
• Research Site — Chengdu
• Research Site — Guangzhou
• Research Site — Nanchang
• Research Site — Nanjing
• Research Site — Nantong
• Research Site — Shandong
• Research Site — Shanghai
• … and 3 more centers

Japan · 8 centers

• Research Site — Chiba
• Research Site — Kashiwa
• Research Site — Kōtoku
• Research Site — Kumamoto
• Research Site — Niigata
• Research Site — Okayama
• Research Site — Osaka
• Research Site — Yokohama

Italy · 6 centers

• Research Site — Alessandria
• Research Site — Bologna
• Research Site — Busto Arsizio
• Research Site — Milan
• Research Site — Milan
• Research Site — Roma

Taiwan · 6 centers

Center list to be confirmed — check the primary protocol.

Germany · 5 centers

• Research Site — Berlin
• Research Site — Chemnitz
• Research Site — Essen
• Research Site — Jena
• Research Site — Würzburg

South Korea · 5 centers

• Research Site — Seoul
• Research Site — Seoul
• Research Site — Seoul
• Research Site — Seoul
• Research Site — Seoul

United Kingdom · 5 centers

Center list to be confirmed — check the primary protocol.

Australia · 4 centers

• Research Site — Heidelberg
• Research Site — Kogarah
• Research Site — Macquarie University
• Research Site — Nedlands

Canada · 4 centers

• Research Site — Barrie
• Research Site — Brampton
• Research Site — Ottawa
• Research Site — Toronto

France · 4 centers

• Research Site — Montpellier
• Research Site — Paris
• Research Site — Pierre-Bénite
• Research Site — Rouen

Brazil · 3 centers

• Research Site — Porto Alegre
• Research Site — São Paulo
• Research Site — São Paulo

Denmark · 3 centers

• Research Site — Aalborg
• Research Site — Copenhagen
• Research Site — Vejle

Spain · 3 centers

• Research Site — Barcelona
• Research Site — Madrid
• … and 1 more center

Hong Kong · 2 centers

• Research Site — Hong Kong
• Research Site — Shatin

Sweden · 2 centers

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT06526793 · D7404C00001 · 2023-505789-27-00

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗