Clinical trial NCT06526793: 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 AZD0486 in Participants With Relapsed or Refractory (R/R) B-cell Non-Hodgkin Lymphoma (SOUNDTRACK-B)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: B-cell Non-Hodgkin Lymphoma
Follicular Lymphoma (FL)
Diffuse Large B-Cell Lymphoma (DLBCL)
Keywords: AZD0486
Follicular Lymphoma (FL)
Diffuse Large B-Cell Lymphoma (DLBCL)
Non-Hodgkin lymphoma (NHL)
Relapsed/Refractory
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2024-07-30
Enrollment: 240
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: The trial will assess AZD0486 monotherapy given by IV infusion. Module 1 will evaluate the efficacy and safety of AZD0486 monotherapy at the recommended Phase 2 dose (RP2D), in participants 18 to 80 years of age, with relapsed or refractory (R/R) follicular lymphoma (FL) who have received ≥ 2 prior therapies. Module 2 will evaluate the efficacy and safety of AZD0486 monotherapy at the RP2D for participants 18 to 80 years of age with (R/R) diffuse large B-cell lymphoma (DLBCL).
Primary purpose: TREATMENT

Brief 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.

Detailed description: 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.

Eligibility criteria: 1. Key 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

   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, 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.

The above is a summary, other exclusion criteria details may apply.

Primary outcomes:
measure: Overall response rate (ORR)
timeFrame: 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 outcomes:
measure: Duration of response (DoR)
timeFrame: To be assessed up to approximately 5 years.
measure: Complete response (CR) rate
timeFrame: To be assessed up through study completion, up to approximately 5 years
measure: Complete response (CR) rate
timeFrame: To be assessed up through study completion, up to approximately 5 years
measure: Overall response rate (ORR)
timeFrame: 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.
measure: Duration of CR (DoCR)
timeFrame: To be assessed up to approximately 5 years.
measure: Time to response (TTR)
timeFrame: From the first dose until the first objective response, up to approximately 5 years.
measure: Event-free survival (EFS)
timeFrame: To be assessed up to approximately 5 years
measure: Progression-free survival (PFS)
timeFrame: To be assessed up to approximately 5 years.
measure: Time to next anti-lymphoma (TTNT)
timeFrame: To be assessed up to approximately 5 years.
measure: Overall survival (OS)
timeFrame: To be assessed up to approximately 5 years.
measure: Minimal residual disease (MRD)
timeFrame: To be assessed up through study completion, up to approximately 5 years
measure: Change from baseline in EORTC IL233 scales
timeFrame: To be assessed up through study completion, up to approximately 5 years
measure: Change from baseline in IL232 QL2 score
timeFrame: To be assessed up through study completion, up to approximately 5 years
measure: Change from baseline in FACT-LymS scales
timeFrame: To be assessed up through study completion, up to approximately 5 years
measure: Change from baseline in PGI-T scale
timeFrame: To be assessed up through study completion, up to approximately 5 years
Other outcomes:
Locations:
city: Duarte
country: United States
facility: Research Site
state: California
city: Tampa
country: United States
facility: Research Site
state: Florida
city: Des Moines
country: United States
facility: Research Site
state: Iowa
city: Overland Park
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facility: Research Site
state: Kansas
city: Rochester
country: United States
facility: Research Site
state: Minnesota
city: Saint Louis
country: United States
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state: Missouri
city: New Brunswick
country: United States
facility: Research Site
state: New Jersey
city: New York
country: United States
facility: Research Site
state: New York
city: Charlotte
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facility: Research Site
state: North Carolina
city: Columbus
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state: Ohio
city: Portland
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state: Oregon
city: Philadelphia
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facility: Research Site
state: Pennsylvania
city: Pittsburgh
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facility: Research Site
state: Pennsylvania
city: Pittsburgh
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state: Pennsylvania
city: Houston
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state: Texas
city: Milwaukee
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state: Wisconsin
city: Heidelberg
country: Australia
facility: Research Site
city: Kogarah
country: Australia
facility: Research Site
city: Macquarie University
country: Australia
facility: Research Site
city: Nedlands
country: Australia
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city: Porto Alegre
country: Brazil
facility: Research Site
city: Sao Paulo
country: Brazil
facility: Research Site
city: Sao Paulo
country: Brazil
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city: Barrie
country: Canada
facility: Research Site
state: Ontario
city: Brampton
country: Canada
facility: Research Site
state: Ontario
city: Ottawa
country: Canada
facility: Research Site
state: Ontario
city: Toronto
country: Canada
facility: Research Site
state: Ontario
city: Chengdu
country: China
facility: Research Site
city: Chengdu
country: China
facility: Research Site
city: Guangzhou
country: China
facility: Research Site
city: Nanchang
country: China
facility: Research Site
city: Nanjing
country: China
facility: Research Site
city: Nantong
country: China
facility: Research Site
city: Shandong
country: China
facility: Research Site
city: Shanghai
country: China
facility: Research Site
city: Tianjin
country: China
facility: Research Site
city: Zhengzhou
country: China
facility: Research Site
city: Aalborg
country: Denmark
facility: Research Site
city: Copenhagen
country: Denmark
facility: Research Site
city: Vejle
country: Denmark
facility: Research Site
city: Montpellier
country: France
facility: Research Site
city: Paris
country: France
facility: Research Site
city: Pierre Bénite
country: France
facility: Research Site
city: Rouen Cedex 1
country: France
facility: Research Site
city: Berlin
country: Germany
facility: Research Site
city: Chemnitz
country: Germany
facility: Research Site
city: Essen
country: Germany
facility: Research Site
city: Jena
country: Germany
facility: Research Site
city: Wuerzburg
country: Germany
facility: Research Site
city: Hong Kong
country: Hong Kong
facility: Research Site
city: Shatin
country: Hong Kong
facility: Research Site
city: Alessandria
country: Italy
facility: Research Site
city: Bologna
country: Italy
facility: Research Site
city: Busto Arsizio
country: Italy
facility: Research Site
city: Milano
country: Italy
facility: Research Site
city: Milan
country: Italy
facility: Research Site
city: Roma
country: Italy
facility: Research Site
city: Chiba-shi
country: Japan
facility: Research Site
city: Kashiwa
country: Japan
facility: Research Site
city: Koto-ku
country: Japan
facility: Research Site
city: Kumamoto-shi
country: Japan
facility: Research Site
city: Niigata-shi
country: Japan
facility: Research Site
city: Okayama-shi
country: Japan
facility: Research Site
city: Osaka-shi
country: Japan
facility: Research Site
city: Yokohama-shi
country: Japan
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Barcelona
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: Pozuelo de Alarcon
country: Spain
facility: Research Site
city: Goteborg
country: Sweden
facility: Research Site
city: Stockholm
country: Sweden
facility: Research Site
city: Kaohsiung City
country: Taiwan
facility: Research Site
city: Kaohsiung
country: Taiwan
facility: Research Site
city: Taichung
country: Taiwan
facility: Research Site
city: Taichung
country: Taiwan
facility: Research Site
city: Tainan City
country: Taiwan
facility: Research Site
city: Taipei City
country: Taiwan
facility: Research Site
city: London
country: United Kingdom
facility: Research Site
city: Manchester
country: United Kingdom
facility: Research Site
city: Norwich
country: United Kingdom
facility: Research Site
city: Nottingham
country: United Kingdom
facility: Research Site
city: Plymouth
country: United Kingdom
facility: Research Site
Study officials:
References: