A Study of AZD0486 Monotherapy or in Combination With Other Anti-Cancer Agents for Mature B-Cell Malignancies
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
- Chronic Lymphocytic Leukaemia
- Small Lymphocytic Lymphoma
- Mantle-cell Lymphoma
- Large B-cell Lymphoma
- B-cell Non-Hodgkin Lymphoma
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
| Arm | Description | Assigned Intervention |
|---|---|---|
|
Experimental Substudy 1 (RR CLL/SLL): Cohort 1A (Surovatamig Monotherapy) |
Participants will receive surovatamig monotherapy as subcutaneous (SC) injection. |
|
|
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. |
|
|
Experimental Substudy 1 (RR CLL/SLL): Cohort 1C (Surovatamig Monotherapy) |
Participants will receive surovatamig monotherapy as intravenous (IV) infusion. |
|
|
Experimental Substudy 2 (RR MCL): Cohort 2A (Surovatamig Monotherapy) |
Participants will receive surovatamig monotherapy as SC injection. |
|
|
Experimental Substudy 2 (RR MCL): Cohort 2C (Surovatamig Monotherapy) |
Participants will receive surovatamig monotherapy as IV infusion. |
|
|
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. |
|
|
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. |
|
Recruiting Locations
Boston, Massachusetts 02215
New Brunswick, New Jersey 08901
New York, New York 10029
Charlotte, North Carolina 28204
Columbus, Ohio 43210
Portland, Oregon 97239
Philadelphia, Pennsylvania 19104
Pittsburgh, Pennsylvania 15232
Providence, Rhode Island 02903
More Details
- NCT ID
- NCT06564038
- Status
- Recruiting
- Sponsor
- AstraZeneca
Study Contact
AstraZeneca Clinical Study Information Center1-877-240-9479
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