AZD0486 as Monotherapy in Participants With Relapsed/Refractory (R/R) B-cell NHL (SOUNDTRACK-B)

AstraZeneca

Status and phase: Enrolling; Phase 2

Conditions: B-cell Non-Hodgkin Lymphoma; Diffuse Large B-Cell Lymphoma (DLBCL); Follicular Lymphoma (FL)

Treatments: Drug: AZD0486

Study type: Interventional

Funder types: Industry

Identifiers

NCT06526793

D7404C00001

2023-505789-27-00 (Registry Identifier)

Details and patient eligibility

About

This is a Phase 2 global, multi-center, open-label study to assess the efficacy, safety and tolerability of AZD0486 monotherapy in adult participants with relapsed/refractory B-cell non-Hodgkin lymphoma (NHL) who have received at least two prior lines of therapies. The study has 2 Modules: Module 1 for FL and Module 2 for DLBCL.

Full description

This is a modular, Phase II, multicenter, single-arm, open-label study to evaluate the efficacy and safety of AZD0486 monotherapy administered as an intravenous (IV) infusion in participants with relapsed or refractory B-NHL. The purpose of this study is to determine the efficacy and safety of AZD0486 administered at the RP2D in adults 18 to 80 years of age with relapsed or refractory B-NHL.

Enrollment: 240 estimated patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

1. Key Inclusion Criteria:

   • Aged 18 to 80 years old

   • Histologically confirmed relapsed refractory FL (Module 1) and DLBCL (Module 2) after at least 2 prior lines of therapy

   • ECOG performance status 0 to 2

   • Locally confirmed CD-19 expression in lymphoma cells after progression from last CD 19 directed therapy

   • FDG-avid disease with at least one bi-dimensionally measurable nodal lesion (defined as > 1.5 cm in its longest dimension), or extranodal lesion (defined as > 1.0 cm in its longest dimension)

   • Adequate hematological function: ANC ≥ 1000/mm3, platelets

     • 75,000/mm3, hemoglobin ≥ 9 g/dL. Transfusion and/or growth factor are allowed but counts must be stable for at least 72 hours afterwards prior to screening

   • Adequate liver function: total bilirubin <1.5x ULN, AST/ALT ≤ 3xULN Note: Patients with documented history of Gilbert's Syndrome and in whom total bilirubin elevations are accompanied by elevated indirect bilirubin are eligible)

   • Adequate renal function: creatinine clearance (CrCl) of ≥ 45 mL/min

   The above is a summary, other inclusion criteria details may apply.

2. Key Exclusion Criteria:

   • Diagnosis of CLL, Burkitt lymphoma, or Richter's transformation
   • Active CNS involvement by B-NHL
   • Leukemic presentation of B-NHL
   • History or presence of clinically relevant CNS pathology such as epilepsy, seizure, paresis, aphasia, stroke, severe brain injuries, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome, or psychosis
   • Prior therapy with T-cell engager (TCE) within 8 weeks, CAR T- cell therapy or autologous Hematopoietic Stem Cell Transplantation (HSCT) within 12 weeks, or prior allogeneic HSCT within 24 weeks of first dose of AZD0486
   • Requires chronic immunosuppressive therapy
   • Unresolved non hematological AEs ≥ Grade 2 from prior therapies; history of ≥ Grade 3 CRS or neurotoxicity from prior CAR-T or TCE therapy
   • History of major cardiac abnormalities.
   • If female, participant must not be pregnant or breastfeeding.

The above is a summary, other exclusion criteria details may apply.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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240 participants in 2 patient groups

Module 1: AZD0486 Monotherapy in Participants with Relapsed or Refractory Follicular Lymphoma

Experimental group

Description:

In Module 1, the efficacy and safety of AZD0486 at the RP2D will be evaluated in R/R FL. AZD0486 will be administered as intravenous infusion.

Treatment:

Drug: AZD0486

Module 2: AZD0486 Monotherapy in Participants with Relapsed or Refractory DLBCL

Experimental group

Description:

In Module 2, the efficacy and safety of AZD0486 at the RP2D will be evaluated in R/R DLBCL. AZD0486 will be administered as intravenous infusion.

Treatment:

Drug: AZD0486