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NCT06564038PHASE1, PHASE2Recruiting

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

AstraZeneca

Start Date

1/30/2025

Completion Date

6/11/2029

Summary

The purpose of this study is to assess the safety and efficacy of surovatamig (formerly AZD0486) administered as monotherapy or in combination with other anticancer agents in participants with hematological malignancies

Detailed Description

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

Age Range: 18 years to No maximum

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.

Interventions

DRUG

Surovatamig

DRUG

Prednisone (or equivalent)

DRUG

Rituximab

DRUG

Cyclophosphamide

DRUG

Vincristine

DRUG

Doxorubicin

DRUG

Acalabrutinib

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Conditions

Chronic Lymphocytic LeukaemiaSmall Lymphocytic LymphomaMantle-cell LymphomaLarge B-cell LymphomaB-cell Non-Hodgkin Lymphoma

Locations

Research Site

Boston, Massachusetts 02215

United States

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Hackensack, New Jersey 07601

United States

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New Brunswick, New Jersey 08901

United States

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New York, New York 10029

United States

Research Site

New York, New York 10065

United States

Research Site

Charlotte, North Carolina 28204

United States

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Charlotte, North Carolina 28204

United States

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Columbus, Ohio 43210

United States

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Portland, Oregon 97239

United States

Research Site

Philadelphia, Pennsylvania 19104

United States

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Pittsburgh, Pennsylvania 15232

United States

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Providence, Rhode Island 02903

United States

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Houston, Texas 77030

United States

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Heidelberg, 3084

Australia

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Melbourne, 3004

Australia

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Nedlands, 6009

Australia

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Beijing, 100044

China

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Guangzhou, 510060

China

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Jinan, 250013

China

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Tianjin, 300060

China

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Zhengzhou, 450008

China

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Ostrava - Poruba, 708 52

Czechia

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Prague, 12808

Czechia

Research Site

Praha 2 - Nové Město, 12820

Czechia

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Aalborg, 9000

Denmark

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Aarhus N, 8200

Denmark

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Copenhagen, 2100

Denmark

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Odense C, 5000

Denmark

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Clermont-Ferrand, 63000

France

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Montpellier, 34295

France

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Paris, 75010

France

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Saint-Cloud, 92210

France

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Villejuif, 94805

France

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Cologne, 50937

Germany

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Homburg, 66421

Germany

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Kiel, 24105

Germany

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Mainz, 55131

Germany

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München, 81377

Germany

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Würzburg, 97080

Germany

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Bologna, 40138

Italy

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Milan, 20141

Italy

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Kōtoku, 135-8550

Japan

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Matsuyama, 791-0280

Japan

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Nagoya, 464-8681

Japan

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Busan, 48108

South Korea

Research Site

Seoul, 02841

South Korea

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Seoul, 03080

South Korea

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Seoul, 05505

South Korea

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Seoul, 06351

South Korea

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Seoul, 06591

South Korea

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Barcelona, 8036

Spain

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Madrid, 28034

Spain

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Madrid, 28040

Spain

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Palma de Mallorca, 7120

Spain

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Santiago de Compostela, 15706

Spain

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Valencia, 46026

Spain

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Changhua, 500

Taiwan

Research Site

Kaohsiung City, 83301

Taiwan

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Tainan, 710

Taiwan

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Taipei, 100

Taiwan

Research Site

Derriford, PL6 5FP

United Kingdom

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London, SE5 9RS

United Kingdom

Research Site

Oxford, 0X3 7LJ

United Kingdom

Research Site

Southampton, SO16 6YD

United Kingdom