AZD0486 1L Therapy for Elderly or Unfit Participants With LBCL

NCT07215585 | Recruiting Phase 3 FDA Drug

• 2 other identifiers: D7402C000012025-522029-37-00
• Study Type: interventional
• Target: 420
• Locations: 11 countries
• Sites: 62

Brief Summary

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.

Conditions

Large B-cell Lymphoma

Keywords

Large B-cell Lymphoma; LBCL; AZD0486; CD3; CD19; TCE; B-cell malignancies; Soundtrack-D2

Outcome Measures

Primary Outcomes (4)

• 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 Outcomes (16)

• Safety Run-In and Phase 3 - ORR

  Up to 7 years

• Safety Run-In and Phase 3 - CR Rate

  Up to 7 years

• Safety Run-In and Phase 3 - DoR

  Up to 7 years

• Safety Run-In and Phase 3 - DoCR

  Up to 7 years

• Safety Run-In and Phase 3 - PFS

  Up to 7 years

Study Arms (3)

Phase III Arm A: R-mini-CHOP and AZD0486

EXPERIMENTAL

2 cycles of R-mini-CHOP followed sequentially by multiple cycles of AZD0486 at RP3D.

Drug: AZD0486; Drug: R-mini-CHOP

Phase III Arm B: R-mini-CHOP

ACTIVE COMPARATOR

6 cycles of R-mini-CHOP per SoC regimen.

Drug: R-mini-CHOP

Safety Run in: R-mini-CHOP and AZD0486

EXPERIMENTAL

2 cycles of R-mini-CHOP followed sequentially by multiple cycles of AZD0486 at RP2D.

Drug: AZD0486; Drug: R-mini-CHOP

Interventions

AZD0486 DRUG

Bispecific monoclonal IgG4 antibody

Also known as: TNB-486

Phase III Arm A: R-mini-CHOP and AZD0486; Safety Run in: R-mini-CHOP and AZD0486

R-mini-CHOP DRUG

Intravenous administration: Rituximab 375 mg/m2, Cyclophosphamide 400 mg/m2, Doxorubicin 25 mg/m2, Vincristine 1 mg, and Oral administration: Prednisone 40 mg/m2

Phase III Arm A: R-mini-CHOP and AZD0486; Phase III Arm B: R-mini-CHOP; Safety Run in: R-mini-CHOP and AZD0486

Eligibility Criteria

• Age: 65 Years - 130 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Older Adult (65+)

You may qualify if:

• 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.
• 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

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (62)

Research Site

Melbourne, 3000, Australia

RECRUITING

Research Site

Nedlands, 6009, Australia

NOT YET RECRUITING

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Waratah, 2298, Australia

NOT YET RECRUITING

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Antwerp, 2030, Belgium

NOT YET RECRUITING

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Brussels, 1200, Belgium

NOT YET RECRUITING

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Ghent, 9000, Belgium

RECRUITING

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Leuven, 3000, Belgium

RECRUITING

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Roeselare, 8800, Belgium

NOT YET RECRUITING

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Yvoir, 5530, Belgium

RECRUITING

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Porto Alegre, 90035-003, Brazil

RECRUITING

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São Paulo, 05652000, Brazil

RECRUITING

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Calgary, Alberta, T2N 5G2, Canada

RECRUITING

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Ottawa, Ontario, K1H 8L6, Canada

RECRUITING

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Beijing, 100730, China

RECRUITING

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Changchun, 130021, China

NOT YET RECRUITING

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Chengdu, 610041, China

NOT YET RECRUITING

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Chongqing, 400042, China

NOT YET RECRUITING

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Fuzhou, 350011, China

NOT YET RECRUITING

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Guangzhou, 510060, China

RECRUITING

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Guangzhou, 510280, China

NOT YET RECRUITING

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Haikou, 570311, China

NOT YET RECRUITING

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Hefei, 230012, China

NOT YET RECRUITING

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Jinan, 250117, China

RECRUITING

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Kunming, 650101, China

NOT YET RECRUITING

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Nanchang, 330000, China

NOT YET RECRUITING

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Nanning, 530021, China

NOT YET RECRUITING

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Nantong, 226001, China

WITHDRAWN

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Shanghai, 200003, China

RECRUITING

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Shanghai, 20032, China

RECRUITING

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Wuhan, 430030, China

NOT YET RECRUITING

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Xiamen, 361003, China

NOT YET RECRUITING

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Hong Kong, 999077, Hong Kong

NOT YET RECRUITING

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Lai Chi Kok, Hong Kong

NOT YET RECRUITING

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Shatin, 00000, Hong Kong

WITHDRAWN

Research Site

Akashi, 673-8558, Japan

NOT YET RECRUITING

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Bunkyō City, 113-8677, Japan

RECRUITING

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Himeji-shi, 670-8540, Japan

NOT YET RECRUITING

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Kōtoku, 135-8550, Japan

RECRUITING

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Kumamoto, 860-8556, Japan

NOT YET RECRUITING

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Matsumoto-shi, 399-8701, Japan

NOT YET RECRUITING

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Matsuyama, 791-0280, Japan

NOT YET RECRUITING

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Meguro-ku, 152-8902, Japan

NOT YET RECRUITING

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Nagoya, 460-0001, Japan

NOT YET RECRUITING

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Osaka, 543-8555, Japan

NOT YET RECRUITING

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Osaka, 545-8586, Japan

RECRUITING

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Otaki-Shi, 739-0696, Japan

NOT YET RECRUITING

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Sunto-gun, 411-8777, Japan

NOT YET RECRUITING

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Yamagata, 990-9585, Japan

RECRUITING

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Yokohama, 241-8515, Japan

RECRUITING

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Kielce, 25-734, Poland

NOT YET RECRUITING

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Krakow, 30-727, Poland

RECRUITING

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Lodz, 93-513, Poland

NOT YET RECRUITING

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Lublin, 20-090, Poland

NOT YET RECRUITING

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Wroclaw, 50-367, Poland

NOT YET RECRUITING

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Seoul, 03080, South Korea

RECRUITING

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Seoul, 5505, South Korea

RECRUITING

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Ankara, 06620, Turkey (Türkiye)

RECRUITING

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Antalya, 07025, Turkey (Türkiye)

RECRUITING

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Glasgow, Scotland, G12 0YN, United Kingdom

NOT YET RECRUITING

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London, NW1 2PG, United Kingdom

RECRUITING

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Newcastle upon Tyne, NE7 7AF, United Kingdom

RECRUITING

Research Site

Nottingham, NG5 1PB, United Kingdom

NOT YET RECRUITING

Study Officials

• Michael Dickinson,, MBBS BS DMSc

  Peter MacCallum Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

AstraZeneca Clinical Study Information Center

CONTACT

1-877-240-9479; information.center@astrazeneca.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: The study consists of 2 sequential parts: a safety run-in (SRI) followed by the phase III.

Study Record Dates

• First Submitted: October 7, 2025
• First Posted: October 10, 2025
• Study Start: November 11, 2025
• Primary Completion (Estimated): June 10, 2030
• Study Completion (Estimated): July 28, 2033
• Last Updated: April 21, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• 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
• 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

Locations

GB (4); KR (2); HK (3); JP (15); CA (2); AU (3); CN (18); PL (5); TU (2); BE (6); BR (2)