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

AstraZeneca

Status and phase

Enrolling

Phase 2

Phase 1

Conditions

B-cell Non-Hodgkin Lymphoma

Small Lymphocytic Lymphoma

Large B-cell Lymphoma

Mantle-cell Lymphoma

Chronic Lymphocytic Leukaemia

Treatments

Drug: Rituximab

Drug: Vincristine

Drug: Cyclophosphamide

Drug: Surovatamig

Drug: Doxorubicin

Drug: Prednisone (or equivalent)

Drug: Acalabrutinib

Study type

Interventional

Funder types

Industry

Identifiers

NCT06564038

2024-515034-33-00 (Registry Identifier)

D7407C00001

Details and patient eligibility

About

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.

Full 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:

Screening period of 28 days
Treatment period
Follow-up period

Enrollment

408 estimated patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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.

Trial design

Primary purpose

Treatment

Allocation

Non-Randomized

Interventional model

Sequential Assignment

Masking

None (Open label)

408 participants in 7 patient groups

Substudy 1 (RR CLL/SLL): Cohort 1A (Surovatamig Monotherapy)

Experimental group

Description:

Participants will receive surovatamig monotherapy as subcutaneous (SC) injection.

Treatment:

Drug: Surovatamig

Substudy 1 (RR CLL/SLL): Cohort 1B (Surovatamig + Acalabrutinib)

Experimental group

Description:

Participants will receive surovatamig as SC injection. Participants will receive acalabrutinib tablet orally twice daily.

Treatment:

Drug: Acalabrutinib

Drug: Surovatamig

Substudy 1 (RR CLL/SLL): Cohort 1C (Surovatamig Monotherapy)

Experimental group

Description:

Participants will receive surovatamig monotherapy as intravenous (IV) infusion.

Treatment:

Drug: Surovatamig

Substudy 2 (RR MCL): Cohort 2A (Surovatamig Monotherapy)

Experimental group

Description:

Participants will receive surovatamig monotherapy as SC injection.

Treatment:

Drug: Surovatamig

Substudy 2 (RR MCL): Cohort 2C (Surovatamig Monotherapy)

Experimental group

Description:

Participants will receive surovatamig monotherapy as IV infusion.

Treatment:

Drug: Surovatamig

Substudy 3 (LBCL): Cohort 3A 2SUD (Surovatamig + RCHOP)

Experimental group

Description:

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.

Treatment:

Drug: Prednisone (or equivalent)

Drug: Doxorubicin

Drug: Surovatamig

Drug: Cyclophosphamide

Drug: Vincristine

Drug: Rituximab

Substudy 3 (LBCL): Cohort 3B 3SUD (Surovatamig + RCHOP)

Experimental group

Description:

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.

Treatment:

Drug: Prednisone (or equivalent)

Drug: Doxorubicin

Drug: Surovatamig

Drug: Cyclophosphamide

Drug: Vincristine

Drug: Rituximab