Purpose

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.

Conditions

Eligibility

Eligible Ages
Over 18 Years
Eligible Sex
All
Accepts 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.

Study Design

Phase
Phase 1/Phase 2
Study Type
Interventional
Allocation
Non-Randomized
Intervention Model
Sequential Assignment
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Substudy 1 (RR CLL/SLL): Cohort 1A (Surovatamig Monotherapy)
Participants will receive surovatamig monotherapy as subcutaneous (SC) injection.
  • Drug: Surovatamig
    Surovatamig will be administered as either SC injection or IV infusion.
    Other names:
    • AZD0486
    • TNB-486
Experimental
Substudy 1 (RR CLL/SLL): Cohort 1B (Surovatamig + Acalabrutinib)
Participants will receive surovatamig as SC injection. Participants will receive acalabrutinib tablet orally twice daily.
  • Drug: Surovatamig
    Surovatamig will be administered as either SC injection or IV infusion.
    Other names:
    • AZD0486
    • TNB-486
  • Drug: Acalabrutinib
    Acalabrutinib will be administered orally
Experimental
Substudy 1 (RR CLL/SLL): Cohort 1C (Surovatamig Monotherapy)
Participants will receive surovatamig monotherapy as intravenous (IV) infusion.
  • Drug: Surovatamig
    Surovatamig will be administered as either SC injection or IV infusion.
    Other names:
    • AZD0486
    • TNB-486
Experimental
Substudy 2 (RR MCL): Cohort 2A (Surovatamig Monotherapy)
Participants will receive surovatamig monotherapy as SC injection.
  • Drug: Surovatamig
    Surovatamig will be administered as either SC injection or IV infusion.
    Other names:
    • AZD0486
    • TNB-486
Experimental
Substudy 2 (RR MCL): Cohort 2C (Surovatamig Monotherapy)
Participants will receive surovatamig monotherapy as IV infusion.
  • Drug: Surovatamig
    Surovatamig will be administered as either SC injection or IV infusion.
    Other names:
    • AZD0486
    • TNB-486
Experimental
Substudy 3 (LBCL): Cohort 3A 2SUD (Surovatamig + RCHOP)
Participants will receive surovatamig as IV infusion with a 2SUD (double step-up dosing) schedule for priming in combination with RCHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) chemotherapy.
  • Drug: Surovatamig
    Surovatamig will be administered as either SC injection or IV infusion.
    Other names:
    • AZD0486
    • TNB-486
  • Drug: Prednisone (or equivalent)
    Prednisone (or equivalent) will be administered either oral or IV infusion as per standard of care.
  • Drug: Rituximab
    Rituximab will be administered as IV infusion as per standard of care.
  • Drug: Cyclophosphamide
    Cyclophosphamide will be administered as IV infusion as per standard of care.
  • Drug: Vincristine
    Vincristine will be administered as IV infusion as per standard of care.
  • Drug: Doxorubicin
    Doxorubicin will be administered as IV infusion as per standard of care.
Experimental
Substudy 3 (LBCL): Cohort 3B 3SUD (Surovatamig + RCHOP)
Participants will receive surovatamig as IV infusion with a 3SUD (triple step-up dosing) schedule for priming in combination with RCHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) chemotherapy.
  • Drug: Surovatamig
    Surovatamig will be administered as either SC injection or IV infusion.
    Other names:
    • AZD0486
    • TNB-486
  • Drug: Prednisone (or equivalent)
    Prednisone (or equivalent) will be administered either oral or IV infusion as per standard of care.
  • Drug: Rituximab
    Rituximab will be administered as IV infusion as per standard of care.
  • Drug: Cyclophosphamide
    Cyclophosphamide will be administered as IV infusion as per standard of care.
  • Drug: Vincristine
    Vincristine will be administered as IV infusion as per standard of care.
  • Drug: Doxorubicin
    Doxorubicin will be administered as IV infusion as per standard of care.

Recruiting Locations

Research Site
Boston, Massachusetts 02215

Research Site
New Brunswick, New Jersey 08901

Research Site
New York, New York 10029

Research Site
Charlotte, North Carolina 28204

Research Site
Columbus, Ohio 43210

Research Site
Portland, Oregon 97239

Research Site
Philadelphia, Pennsylvania 19104

Research Site
Pittsburgh, Pennsylvania 15232

Research Site
Providence, Rhode Island 02903

More Details

NCT ID
NCT06564038
Status
Recruiting
Sponsor
AstraZeneca

Study Contact

AstraZeneca Clinical Study Information Center
1-877-240-9479
information.center@astrazeneca.com

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

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.