Surovatamig: Surovatamig will be administered as either SC injection or IV infusion.
Prednisone (or equivalent): Prednisone (or equivalent) will be administered either oral or IV infusion as per standard of care.
Rituximab: Rituximab will be administered as IV infusion as per standard of care.
Cyclophosphamide: Cyclophosphamide will be administered as IV infusion as per standard of care.
Vincristine: Vincristine will be administered as IV infusion as per standard of care.
Doxorubicin: Doxorubicin will be administered as IV infusion as per standard of care.
Acalabrutinib: Acalabrutinib will be administered orally
Study 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
Eligibility
Sex
ALL
Min age
18 Years
Max age
—
Healthy volunteers
No
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.
Primary outcome measure(s)
Number of Participants with Adverse Events, Serious Adverse Events and Adverse Events of Special Interest — Up to 6 years 4 months Safety and tolerability of surovatamig as monotherapy and in combination with other anticancer agents across mature B-cell malignancies.
Number of Participants with Dose Limiting Toxicity (DLTs) — Up to 2 months Safety and tolerability of surovatamig as monotherapy and in combination with other anticancer agents across mature B-cell malignancies.
Trial sites (65)
Facility
City
Region
Status
Research Site
Boston
Massachusetts
Recruiting
Research Site
Hackensack
New Jersey
Recruiting
Research Site
New Brunswick
New Jersey
Recruiting
Research Site
New York
New York
Recruiting
Research Site
New York
New York
Withdrawn
Research Site
Charlotte
North Carolina
Recruiting
Research Site
Charlotte
North Carolina
Not Yet Recruiting
Research Site
Columbus
Ohio
Recruiting
Research Site
Portland
Oregon
Recruiting
Research Site
Philadelphia
Pennsylvania
Recruiting
Research Site
Pittsburgh
Pennsylvania
Recruiting
Research Site
Providence
Rhode Island
Recruiting
Research Site
Houston
Texas
Not Yet Recruiting
Research Site
Heidelberg
Australia
Recruiting
Research Site
Melbourne
Australia
Recruiting
Research Site
Nedlands
Australia
Recruiting
Research Site
Beijing
China
Recruiting
Research Site
Guangzhou
China
Recruiting
Research Site
Jinan
China
Withdrawn
Research Site
Tianjin
China
Recruiting
Research Site
Zhengzhou
China
Recruiting
Research Site
Ostrava - Poruba
Czechia
Recruiting
Research Site
Prague
Czechia
Recruiting
Research Site
Praha 2 - Nové Město
Czechia
Recruiting
Research Site
Aalborg
Denmark
Recruiting
Research Site
Aarhus N
Denmark
Recruiting
Research Site
Copenhagen
Denmark
Recruiting
Research Site
Odense C
Denmark
Recruiting
Research Site
Clermont-Ferrand
France
Not Yet Recruiting
Research Site
Montpellier
France
Recruiting
Research Site
Paris
France
Recruiting
Research Site
Saint-Cloud
France
Recruiting
Research Site
Villejuif
France
Recruiting
Research Site
Cologne
Germany
Not Yet Recruiting
Research Site
Homburg
Germany
Not Yet Recruiting
Research Site
Kiel
Germany
Recruiting
Research Site
Mainz
Germany
Not Yet Recruiting
Research Site
München
Germany
Recruiting
Research Site
Würzburg
Germany
Recruiting
Research Site
Bologna
Italy
Not Yet Recruiting
+ 25 more sites — see the full list on the official registry below.
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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