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A Study of AZD0486 Monotherapy or in Combination With Other Anti-Cancer Agents for Mature B-Cell Malignancies

NCT06564038 · AstraZeneca
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Official title
A Phase I/II Open-Label Multi-Centre Master Protocol to Evaluate the Safety and Efficacy of AZD0486 Monotherapy or in Combination With Other Anticancer Agents in Participants With Mature B-Cell Malignancies
About this study
This is open-label, multi-center study to evaluate the safety and preliminary efficacy of surovatamig administered as monotherapy and in combination with other anticancer agents in participants with mature B-cell hematologic malignancies. This master study currently includes 3 substudies and each substudy focusing on a defined population: Substudy 1: Relapsed/refractory (R/R) Chronic lymphocytic leukaemia (CLL)/ Small lymphocytic lymphoma (SLL) Substudy 2: R/R Mantle-cell lymphoma (MCL) Substudy 3: Large B-cell lymphoma (LBCL) or R/R B-cell non-Hodgkin lymphoma (B-NHL) (not applicable to US) The study will have the following sequential periods: 1. Screening period of 28 days 2. Treatment period 3. Follow-up period
Eligibility criteria
Inclusion Criteria: Master Inclusion Criteria applicable to all substudies: * Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2. * Contraception use during treatment and at least 90 days after final dose. * Confirmed CD19 expression if prior anti-CD19 therapy. Substudy 1 Specific Inclusion Criteria: * Participants with CLL must require treatment according to the international workshop on Chronic Lymphocytic Leukemia (iwCLL) criteria. * SLL: at least 1 measurable site per Lugano. * Absolute lymphocyte count (ALC) \<25000 cells/mcL. * Cohort 1A and 1C: at least 2 prior lines of systemic therapy for CLL/SLL. * Cohort 1B: at least 1 prior line of therapy and is bruton tyrosine kinase inhibitor (BTKi)-sensitive. Substudy 2 Specific Inclusion Criteria: * MCL diagnosis per WHO. * Clinical Stage II, III, or IV by Ann Arbor Classification. * At least 1 measurable site per Lugano. * ALC \< 25000 cells/mcL. * Cohort 2A and 2C: Relapse or progressed after 2 or more lines of therapy including BTKi. Substudy 3 Specific Inclusion Criteria: * At least 1 measurable site as per Lugano. * Left ventricular ejection fraction (LVEF) ≥50%. * Participant must be no older than 79 years of age at the time of signing ICF. * Contraception at least 90 days after last dose of surovatamig or 4 months after last dose of vincristine, and 6 months after the last dose of cyclophosphamide, or doxorubicin. * Cohort 3A: 1. Histologically confirmed diagnosis of previously untreated large B-cell Lymphoma (LBCL) per WHO 2022. 2. R/R B-NHL after at least 1 prior lines of systemic therapy. 3. International Prognostic Index (IPI) 2-5. * Cohort 3B: 1. Histologically confirmed diagnosis of previously untreated large B-cell Lymphoma (LBCL) per WHO 2022. 2. IPI score of 2 to 5. Exclusion Criteria: Master Exclusion Criteria applicable to all substudies: * Central nervous system (CNS) lymphoma. * Surgery within 14 days of study drug. * Clinically significant cardiovascular (CV) disease. * Unresolved Grade \>2 AEs from prior anticancer therapy (except alopecia or fatigue). * Any systemic therapy within 5 half-lives or 21 days (whichever is shorter) prior to treatment. * Radiation therapy within 28 days. * Prior CAR T-cell therapy or autologous-haematopoietic stem cell transplant (HSCT) within 12 weeks or prior T-cell engager (TCE) within 8 weeks. * Prior Grade \> 3 cytokine release syndrome (CRS) or immune effector cell-associated neurotoxicity syndrome (ICANS) event. * Prior allogeneic HSCT or solid organ transplantation within 24 weeks of starting Cycle 1 Day 1. * Active, significant, uncontrolled infection or autoimmune disease requiring systemic therapy including participants with known history of haemophagocytic lymphohistiocytosis (HLH). Substudy 1 Specific Exclusion Criteria: * CLL/SLL transformation to more aggressive form of lymphoma. * Cohort 1B: bleeding diathesis, CYP3A inhibitor or inducer, history of ICH or stroke within 24 weeks, GI malabsorption, receiving vitamin K antagonist. Substudy 3 Specific Exclusion Criteria: * Mediastinal grey-zone lymphoma, Burkitt, Richter's transformation, primary effusion large B-cell lymphoma (LBCL). * Cumulative dose of anthracycline \>150 mg/m2.
Study design
Enrollment target: 408 participants
Allocation: non_randomized
Masking: none
Age groups: adult, older_adult
Timeline
Starts: 2025-01-30
Estimated completion: 2029-06-11
Last updated: 2026-05-14
Interventions
Drug: SurovatamigDrug: Prednisone (or equivalent)Drug: RituximabDrug: CyclophosphamideDrug: VincristineDrug: DoxorubicinDrug: Acalabrutinib
Primary outcomes
  • Number of Participants with Adverse Events, Serious Adverse Events and Adverse Events of Special Interest (Up to 6 years 4 months)
  • Number of Participants with Dose Limiting Toxicity (DLTs) (Up to 2 months)
Sponsor
AstraZeneca · industry
Contacts & investigators
ContactAstraZeneca Clinical Study Information Center · contact · information.center@astrazeneca.com · 1-877-240-9479
All locations (64)
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Boston, Massachusetts, United States
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Hackensack, New Jersey, United States
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New Brunswick, New Jersey, United States
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New York, New York, United States
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New York, New York, United States
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Charlotte, North Carolina, United States
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Charlotte, North Carolina, United States
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Columbus, Ohio, United States
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Portland, Oregon, United States
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Philadelphia, Pennsylvania, United States
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Pittsburgh, Pennsylvania, United States
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Providence, Rhode Island, United States
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Houston, Texas, United States
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Heidelberg, Australia
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Melbourne, Australia
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Nedlands, Australia
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Beijing, China
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Guangzhou, China
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Jinan, China
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Tianjin, China
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Zhengzhou, China
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Ostrava - Poruba, Czechia
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Prague, Czechia
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Praha 2 - Nové Město, Czechia
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Aalborg, Denmark
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Aarhus N, Denmark
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Copenhagen, Denmark
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Odense C, Denmark
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Clermont-Ferrand, France
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Montpellier, France
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Paris, France
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Saint-Cloud, France
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Villejuif, France
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Cologne, Germany
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Homburg, Germany
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Kiel, Germany
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Mainz, Germany
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München, Germany
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Würzburg, Germany
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Bologna, Italy
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Milan, Italy
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Kōtoku, Japan
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Matsuyama, Japan
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Nagoya, Japan
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Busan, South Korea
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Seoul, South Korea
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Seoul, South Korea
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Seoul, South Korea
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Seoul, South Korea
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Seoul, South Korea
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Barcelona, Spain
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Madrid, Spain
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Madrid, Spain
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Palma de Mallorca, Spain
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Santiago de Compostela, Spain
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Valencia, Spain
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Changhua, Taiwan
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Kaohsiung City, Taiwan
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Tainan, Taiwan
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Taipei, Taiwan
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Derriford, United Kingdom
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London, United Kingdom
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Oxford, United Kingdom
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Southampton, United Kingdom
A Study of AZD0486 Monotherapy or in Combination With Other Anti-Cancer Agents for Mature B-Cell Malignancies · TrialPath