AZD0486 1L Therapy for Elderly or Unfit Participants With LBCL (SOUNDTRACK-D2)

A Phase III, Multicentre, Open-Label, Randomised Study Evaluating the Efficacy and Safety of R-mini-CHOP x2 Followed by AZD0486 Versus R-mini-CHOP x6 in Elderly or Unfit Participants With Newly Diagnosed Large B-cell Lymphoma (SOUNDTRACK-D2)

The purpose of this study is to measure the efficacy and safety of R-mini-CHOP × 2 followed by AZD0486 compared with R-mini-CHOP × 6 in elderly or unfit participants newly diagnosed with LBCL.

Study Overview

• Status: Recruiting
• Conditions: Large B-cell Lymphoma
• Intervention / Treatment: Drug: AZD0486; Drug: R-mini-CHOP

• Study Type: Interventional
• Enrollment (Estimated): 420
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: AstraZeneca Clinical Study Information Center; Phone Number: 1-877-240-9479; Email: information.center@astrazeneca.com

Study Locations

• Australia
  • Clayton, Australia, 3168
    • Not yet recruiting
    • Research Site
  • Macquarie University, Australia, 2109
    • Withdrawn
    • Research Site
  • Melbourne, Australia, 3000
    • Recruiting
    • Research Site
  • Nedlands, Australia, 6009
    • Not yet recruiting
    • Research Site
  • Waratah, Australia, 2298
    • Not yet recruiting
    • Research Site
• Belgium
  • Antwerp, Belgium, 2030
    • Withdrawn
    • Research Site
  • Brussels, Belgium, 1200
    • Not yet recruiting
    • Research Site
  • Ghent, Belgium, 9000
    • Recruiting
    • Research Site
  • Leuven, Belgium, 3000
    • Recruiting
    • Research Site
  • Roeselare, Belgium, 8800
    • Suspended
    • Research Site
  • Yvoir, Belgium, 5530
    • Recruiting
    • Research Site
• Brazil
  • Porto Alegre, Brazil, 90035-003
    • Recruiting
    • Research Site
  • São Paulo, Brazil, 05652000
    • Recruiting
    • Research Site
• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 5G2
      • Recruiting
      • Research Site
  • British Columbia
    • Victoria, British Columbia, Canada, V8R 6V5
      • Not yet recruiting
      • Research Site
  • Ontario
    • Hamilton, Ontario, Canada, L8V 5C2
      • Not yet recruiting
      • Research Site
    • Ottawa, Ontario, Canada, K1H 8L6
      • Recruiting
      • Research Site
• China
  • Beijing, China, 100730
    • Recruiting
    • Research Site
  • Changchun, China, 130021
    • Recruiting
    • Research Site
  • Chengdu, China, 610041
    • Recruiting
    • Research Site
  • Chongqing, China, 400042
    • Not yet recruiting
    • Research Site
  • Fuzhou, China, 350011
    • Not yet recruiting
    • Research Site
  • Guangzhou, China, 510060
    • Recruiting
    • Research Site
  • Guangzhou, China, 510280
    • Not yet recruiting
    • Research Site
  • Haikou, China, 570311
    • Not yet recruiting
    • Research Site
  • Hefei, China, 230012
    • Not yet recruiting
    • Research Site
  • Jinan, China, 250117
    • Recruiting
    • Research Site
  • Kunming, China, 650101
    • Not yet recruiting
    • Research Site
  • Nanchang, China, 330000
    • Not yet recruiting
    • Research Site
  • Nanning, China, 530021
    • Not yet recruiting
    • Research Site
  • Nantong, China, 226001
    • Withdrawn
    • Research Site
  • Shanghai, China, 20032
    • Recruiting
    • Research Site
  • Shanghai, China, 200003
    • Recruiting
    • Research Site
  • Wuhan, China, 430030
    • Not yet recruiting
    • Research Site
  • Xiamen, China, 361003
    • Not yet recruiting
    • Research Site
• Hong Kong
  • Hong Kong, Hong Kong, 999077
    • Recruiting
    • Research Site
  • Lai Chi Kok, Hong Kong
    • Not yet recruiting
    • Research Site
  • Shatin, Hong Kong, 00000
    • Withdrawn
    • Research Site
• Japan
  • Akashi, Japan, 673-8558
    • Not yet recruiting
    • Research Site
  • Bunkyō City, Japan, 113-8677
    • Recruiting
    • Research Site
  • Himeji-shi, Japan, 670-8540
    • Not yet recruiting
    • Research Site
  • Kumamoto, Japan, 860-8556
    • Not yet recruiting
    • Research Site
  • Kōtoku, Japan, 135-8550
    • Recruiting
    • Research Site
  • Matsumoto-shi, Japan, 399-8701
    • Not yet recruiting
    • Research Site
  • Matsuyama, Japan, 791-0280
    • Not yet recruiting
    • Research Site
  • Meguro-ku, Japan, 152-8902
    • Not yet recruiting
    • Research Site
  • Nagoya, Japan, 460-0001
    • Not yet recruiting
    • Research Site
  • Okayama, Japan, 701-1192
    • Not yet recruiting
    • Research Site
  • Osaka, Japan, 545-8586
    • Recruiting
    • Research Site
  • Osaka, Japan, 543-8555
    • Not yet recruiting
    • Research Site
  • Otaki-Shi, Japan, 739-0696
    • Not yet recruiting
    • Research Site
  • Sapporo, Japan, 003-0804
    • Not yet recruiting
    • Research Site
  • Sunto-gun, Japan, 411-8777
    • Not yet recruiting
    • Research Site
  • Yamagata, Japan, 990-9585
    • Recruiting
    • Research Site
  • Yokohama, Japan, 241-8515
    • Recruiting
    • Research Site
• Poland
  • Kielce, Poland, 25-734
    • Not yet recruiting
    • Research Site
  • Krakow, Poland, 30-727
    • Recruiting
    • Research Site
  • Lodz, Poland, 93-513
    • Not yet recruiting
    • Research Site
  • Lublin, Poland, 20-090
    • Not yet recruiting
    • Research Site
  • Wroclaw, Poland, 50-367
    • Not yet recruiting
    • Research Site
• South Korea
  • Seoul, South Korea, 03080
    • Recruiting
    • Research Site
  • Seoul, South Korea, 5505
    • Recruiting
    • Research Site
• Turkey (Türkiye)
  • Ankara, Turkey (Türkiye), 06620
    • Recruiting
    • Research Site
  • Antalya, Turkey (Türkiye), 07025
    • Recruiting
    • Research Site
• United Kingdom
  • Glasgow, Scotland, United Kingdom, G12 0YN
    • Not yet recruiting
    • Research Site
  • London, United Kingdom, NW1 2PG
    • Recruiting
    • Research Site
  • Newcastle upon Tyne, United Kingdom, NE7 7AF
    • Recruiting
    • Research Site
  • Nottingham, United Kingdom, NG5 1PB
    • Not yet recruiting
    • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion criteria:

• Participants are either 80 years of age or older, OR 65 to 79 years of age or older and classified as unfit per sGA, and otherwise not considered candidates for full-dose R-CHOP per investigator assessment;
• Histologically confirmed diagnosis of previously untreated LBCL as per WHO-HEM5 (excluding plasmablastic lymphoma) and follicular large cell lymphoma;
• FDG-avid and measurable disease as per Lugano and Ann Arbor staging;
• Stage I bulky (7.5 cm and greater) to Stage IV;
• ECOG performance status 0 to 2;
• Adequate bone marrow, liver, renal and cardiac function.

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

• As judged by the investigator, any evidence of diseases which make it undesirable for the participant to participate in the study, or that would jeopardise compliance with the protocol
• Diagnosis of post-transplant lymphoproliferative disease, plasmablastic lymphoma, Richter's transformation, prior history of or concurrent indolent lymphoma (including de novo transformed or composite lymphoma).
• History of CNS involvement by their B-NHL or history of clinically relevant CNS medical condition
• Known history of hemophagocytic lymphohistiocytosis/macrophage activation syndrome (HLH/MAS).
• Active or uncontrolled infection
• Major cardiac abnormalities
• Prior anti-lymphoma therapy except for corticosteroids for symptom control
• Requires chronic immunosuppressive therapy for active autoimmune/inflammatory condition, with some exceptions

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Phase III Arm A: R-mini-CHOP and AZD0486; 2 cycles of R-mini-CHOP followed sequentially by multiple cycles of AZD0486 at RP3D.	Drug: AZD0486; Bispecific monoclonal IgG4 antibody; Other Names: TNB-486; Drug: R-mini-CHOP; Intravenous administration: Rituximab 375 mg/m2, Cyclophosphamide 400 mg/m2, Doxorubicin 25 mg/m2, Vincristine 1 mg, and Oral administration: Prednisone 40 mg/m2
Active Comparator: Phase III Arm B: R-mini-CHOP; 6 cycles of R-mini-CHOP per SoC regimen.	Drug: R-mini-CHOP; Intravenous administration: Rituximab 375 mg/m2, Cyclophosphamide 400 mg/m2, Doxorubicin 25 mg/m2, Vincristine 1 mg, and Oral administration: Prednisone 40 mg/m2
Experimental: Safety Run in: R-mini-CHOP and AZD0486; 2 cycles of R-mini-CHOP followed sequentially by multiple cycles of AZD0486 at RP2D.	Drug: AZD0486; Bispecific monoclonal IgG4 antibody; Other Names: TNB-486; Drug: R-mini-CHOP; Intravenous administration: Rituximab 375 mg/m2, Cyclophosphamide 400 mg/m2, Doxorubicin 25 mg/m2, Vincristine 1 mg, and Oral administration: Prednisone 40 mg/m2

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
SRI - Safety evaluation of R-mini-CHOP × 2 followed by AZD0486: Number of participants with treatment-related adverse events.	Incidence and severity of AEs, SAEs, AESIs, and events of clinical interest based on NCI CTCAE v5.0/ASTCT, vital signs, laboratory parameters.	Up to 1 year
SRI - Tolerability evaluation of R-mini-CHOP × 2 followed by AZD0486: Number of participants with treatment-related adverse events.	AEs leading to study treatment discontinuation or dose modification based on NCI CTCAE v5.0/ASTCT, vital signs, laboratory parameters.	Up to 1 year
SRI - Determination of the recommended Phase III dose (RP3D)	The RP3D will be the dose of AZD0486 selected for the Phase 3 part based on safety data compiled during the Safety Run-In part	Up to 1 year
Phase 3 - To demonstrate the superiority of R-mini-CHOP x2 followed by AZD0486 compared to R-mini-CHOP x6 regimen.	Progression-free Surival (PFS), based on Lugano 2014 Response Criteria.	Up to 7 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety Run-In and Phase 3 - ORR	ORR defined as the proportion of participants achieving either a PR or CR at timepoints defined in the study protocol, based on Lugano 2014 Response Criteria as determined by Investigator assessment.	Up to 7 years
Safety Run-In and Phase 3 - CR Rate	CR rate is defined as the proportion of participants achieving a CR at timepoints defined in the study protocol, based on Lugano 2014 Response Criteria as determined by Investigator assessment.	Up to 7 years
Safety Run-In and Phase 3 - DoR	DoR is defined as the time from the date of first documented response until the date of documented progression based on Lugano 2014 criteria as determined by Investigator assessment or death due to any cause.	Up to 7 years
Safety Run-In and Phase 3 - DoCR	DoCR is defined as the time from the date of first documented CR until the date of documented progression or death due to any cause, as assessed by the Investigator.	Up to 7 years
Safety Run-In and Phase 3 - PFS	PFS is defined as the time from date of the first dose to date of documented objective disease progression as per Lugano 2014 or death (by any cause in the absence of progression), as determined by Investigator assessment.	Up to 7 years
Safety Run In and Phase 3 - OS	OS defined as the time from date of the first dose until death due to any cause.	Up to 7 years
Phase 3 - Time from randomisation to second progression or death (PFS2)	PFS2 is defined as the time from randomisation to the earliest of the progression event (following the initial investigator-assessed progression), after first subsequent therapy, or death.	Up to 7 years
Phase 3 - Time to First Subsequent Therapy or Death (TFST)	TFST is defined as time from randomisation until the start date of first subsequent anti-lymphoma therapy after discontinuation of randomised treatment, or death due to any cause.	Up to 7 Years
Phase 3 - Safety evaluation of R-mini-CHOP × 2 followed by AZD0486: Number of participants with treatment-related adverse events.	Incidence and severity of AEs, SAEs, AESIs, and events of clinical interest based on NCI CTCAE v5.0/ASTCT, vital signs, laboratory parameters.	Up to 7 years
Phase 3 - Tolerability evaluation of R-mini-CHOP × 2 followed by AZD0486: Number of participants with treatment-related adverse events.	AEs leading to study treatment discontinuation or dose modification based on NCI CTCAE v5.0/ASTCT, vital signs, laboratory parameters.	Up to 7 years
Safety Run-In and Phase 3 - Pharmacokinetics of AZD0486: serum concentration of study drug	Maximum observed serum concentration of AZD0486.	Up to 7 years
Safety Run-In and Phase 3 - Pharmacokinetics of AZD0486: Maximum plasma concentration of the study drug (Cmax).	Maximum observed plasma concentration of AZD0486.	Up to 7 years
Safety Run-In and Phase 3 - Pharmacokinetics of AZD0486: Concentration of study drug reached before next dose (Ctrough).	Observed plasma concentration of AZD0486 right before next dose of AZD0486.	Up to 7 years
Safety Run-In and Phase 3 - To determine the immunogenicity of AZD0486	Summary of pre-existing and treatment induced ADAs for AZD0486 (positive or negative, titres) and the impact on PK, efficacy or safety.	Up to 7 years
Phase 3 - Safety evaluation of R-mini-CHOP × 2 followed by AZD0486 versus R-mini-CHOP × 6	Evaluation of key participant-reported side effects (pain, fatigue) and overall treatment tolerability, lymphoma-specific concerns, and HRQoL.	Up to 7 years
Phase 3 - Efficacy evaluation of R-mini-CHOP × 2 followed by AZD0486 versus R-mini-CHOP × 6	Evaluation of key participant-reported side effects (pain, fatigue) and overall treatment tolerability, lymphoma-specific concerns, and HRQoL.	Up to 7 years

Collaborators and Investigators

• Sponsor: AstraZeneca
• Investigators: Principal Investigator: Michael Dickinson,, MBBS BS DMSc, Peter MacCallum Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): November 11, 2025
• Primary Completion (Estimated): June 10, 2030
• Study Completion (Estimated): July 28, 2033

Study Registration Dates

• First Submitted: October 7, 2025
• First Submitted That Met QC Criteria: October 7, 2025
• First Posted (Actual): October 10, 2025

Study Record Updates

• Last Update Posted (Actual): June 18, 2026
• Last Update Submitted That Met QC Criteria: June 17, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: CD19; B-cell malignancies; TCE; Large B-cell Lymphoma; LBCL; CD3; AZD0486; Soundtrack-D2
• Other Study ID Numbers: D7402C00001; 2025-522029-37-00 (Registry Identifier: CTIS)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure
• IPD Sharing Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure
• IPD Sharing Access Criteria: When a request has been approved AstraZeneca will provide access to the anonymized individual patient-level data via secure research environment Vivli.org. A Signed Data Usage Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No