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AzTrials

Diffuse Large B-cell LymphomaPhase 1/2NCT03677154

Trial of Mosunetuzumab (BTCT4465A) as Consolidation Therapy in Participants With Diffuse Large B-Cell Lymphoma Following First-Line Immunochemotherapy and as Monotherapy or in Combination With Polatuzumab Vedotin in Elderly/Unfit Participants With Previously Untreated Diffuse Large B-Cell Lymphoma

A Phase 1/2 study testing Mosunetuzumab Intravenous (IV), Mosunetuzumab Subcutaneous (SC) and Polatuzumab Vedotin in people with Diffuse Large B-cell Lymphoma, run by Hoffmann-La Roche at 32 sites in 6 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

This study will evaluate the safety, pharmacokinetics, and preliminary efficacy of mosunetuzumab following first-line diffuse large B-cell lymphoma (DLBCL) immunochemotherapy in participants with a best response of stable disease or partial response, or in elderly/unfit participants with previously untreated DLBCL, or… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Diffuse Large B-cell Lymphoma
What is being tested?
Mosunetuzumab Intravenous (IV), Mosunetuzumab Subcutaneous (SC) and Polatuzumab Vedotin
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
188 participants
Where
32 sitesin 6 countries
Study dates
23 May 2019to 7 Aug 2025
Phase
Phase 1/2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • At least one bi-dimensionally measurable nodal lesion, defined as > 1.5 cm in its longest dimension, or one bi-dimensionally measurable extranodal lesion, defined as > 1.0 cm in its longest diameter
  • Adequate hematologic function
  • Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1, or 2; with the exception of South Korea, where participants 80 years or older with ECOG >/= 2 will not be eligible
  • Participants in Cohort A must also meet the following criteria for study entry:
  • Histologically confirmed DLBCL according to World Health Organization (WHO) 2016 expected to express the cluster of differentiation-20 (CD20) antigen
  • One prior therapy with any systemic anthracycline-based chemoimmunotherapy containing regimen for previously untreated DLBCL
Show all 12Show fewer
  • Best response of SD or PR to prior systemic chemoimmunotherapy at the end of induction treatment in accordance with the Lugano 2014 criteria
  • Participants in Cohorts B and C must also meet the following criteria for study entry:
  • Previously untreated, histologically confirmed, DLBCL according to WHO 2016 classification
  • Age >/= 80 years, or
  • Age 65-79 years and considered ineligible for chemoimmuotherapy (R-CHOP) with at least one of the following: Impairment in at least two activity of daily living (ADL) components as defined in the protocol; impairment in at least two instrumental ADL components as defined in the protocol; cumulative illness rating scale - geriactic (CIRS-G) score of at least one cormorbidity with a severity score of 3-4 (not including lymphoma and hematologic deficiencies due to lymphoma) or a score of 2 in >/= 8 comorbidities; impairment in cardiac function, renal function, liver function, or other comorbidities such that the participant is unfit for full-dose immunochemotherapy, such as rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP)
  • Participants with an initial ECOG performance status of 3 may be considered during screening if the performance status is DLBCL-related and if pre-phase treatment during the screening phase (not more than 100 mg/day up to 7 days prior to Cycle 1 Day 1) results in an improvement of ECOG performance status to </= 2 prior to enrollment

Who cannot join

  • Participants who meet any of the following criteria will be excluded from study entry:
  • Transformed lymphoma
  • CNS lymphoma
  • Prior treatment with mosunetuzumab
  • Prior stem cell transplant (autologous and allogeneic)
  • History of confirmed progressive multifocal leukoencephalopathy (PML)
Show all 20Show fewer
  • Known or suspected chronic active Epstein Barr virus (CAEBV), hepatitis B, hepatitis C (HCV), or Human Immunodeficiency Virus (HIV)
  • Known or suspected history of hemophagocytic lymphohistiocytosis (HLH)
  • Positive SARS-CoV-2 antigen or PCR test within 30 days prior to Cycle 1 Day 1
  • Prior solid organ transplantation
  • Current or past history of central nervous system (CNS) disease, such as stroke, epilepsy, CNS vasculitis, or neurodegenerative disease
  • Clinically significant history of liver disease
  • Prior treatment with radiotherapy within 2 weeks prior to Cycle 1, Day 1 (C1D1)
  • Significant cardiovascular disease
  • Participants in Cohort A who meet the following criteria will be excluded from study entry:
  • Prior anti-lymphoma treatment with chemotherapy, immunotherapy, or biologic therapy 4 weeks prior to C1D1
  • Participants in Cohorts B and C who meet the following criterion will be excluded from study entry:
  • Prior treatment for DLBCL with chemotherapy, immunotherapy, and biologic therapy
  • Participants in Cohort C who meet the following criteria will be excluded from study entry:
  • Current Grade >1 peripheral neuropathy by clinical examination or demyelinating form of Charcot-Marie-Tooth disease

Trial locations and contacts

32 sites in 6 countries.

32 sites in 6 countries

United States8 sites

  • University of Maryland Medical Center

    Baltimore, Maryland, 21201

  • University of Alabama at Birmingham School of Medicine

    Birmingham, Alabama, 352331912

  • Texas Oncology - Baylor Charles A. Sammons Cancer Center

    Dallas, Texas, 75246

  • Duke University

    Durham, North Carolina, 27708-9963

  • Fort Wayne Medical Institute

    Fort Wayne, Indiana, 46805

  • Fox Chase Cancer Center

    Philadelphia, Pennsylvania, 19111

  • Rhode Island Hospital

    Providence, Rhode Island, 02903

  • University of California, Los Angeles (UCLA) - Hematology/Oncology Santa Monica

    Santa Monica, California, 90404-2023

Other trials in United States

Israel7 sites

  • Soroka Medical Center

    Beersheba, 8410101

  • Rambam Medical Center

    Haifa, 31096

  • Carmel medical center

    Haifa, 3436212

  • Shaare Zedek Medical Center

    Jerusalem, 9103102

  • Hadassah Ein-Karem

    Jerusalem, 91120

  • Meir Medical Center

    Kfar Saba, 4428164

  • Sheba Medical Center

    Ramat Gan, 5262100

Other trials in Israel

South Korea6 sites

  • Pusan National University Hospital

    Busan, 49241

  • Keimyung University Dongsan Hospital

    Daegu, 41931

  • Samsung Medical Center

    Seoul, (0)6351

  • The Catholic University of Korea Yeouido St. Mary's Hospital

    Seoul, (0)7345

  • Seoul National University Hospital

    Seoul, 03080

  • Severance Hospital, Yonsei University

    Seoul, 03722

Other trials in South Korea

Spain6 sites

  • Hospital Universitario Vall d Hebron

    Barcelona, 08035

  • Institut Catala d Oncologia Hospitalet

    Barcelona, 08908

  • Hospital San Pedro de Alcantara

    Cáceres, 10003

  • Hospital General Universitario Gregorio Marañon

    Madrid, 28007

  • Hospital Universitario 12 de Octubre

    Madrid, 28041

  • Hospital Universitario Virgen Macarena

    Seville, Sevilla, 41071

Other trials in Spain

Poland4 sites

  • Uniwersyteckie Centrum Kliniczne

    Gdansk, 80-214

  • PRATIA MCM Kraków

    Krakow, 30-727

  • Centrum Onkologii Ziemi Lubelskiej im. ?w. Jana z Dukli

    Lublin, 20-090

  • Szpital Wojewodzki w Opolu

    Opole, 45-372

Other trials in Poland

Taiwan1 site

  • National Taiwan University Hospital

    Taipei, 10002

Other trials in Taiwan

About this study

Official title: A Phase I/II Trial of Mosunetuzumab (BTCT4465A) as Consolidation Therapy in Patients With Diffuse Large B-Cell Lymphoma Following First-Line Immunotherapy and as Monotherapy or in Combination With Polatuzumab Vedotin in Elderly/Unfit Patients With Previously Untreated Diffuse Large B-Cell Lymphoma

This study will evaluate the safety, pharmacokinetics, and preliminary efficacy of mosunetuzumab following first-line diffuse large B-cell lymphoma (DLBCL) immunochemotherapy in participants with a best response of stable disease or partial response, or in elderly/unfit participants with previously untreated DLBCL, or subcutaneous mosunetuzumab in combination with polatuzumab vedotin IV in elderly/unfit participants with previously untreated DLBCL.

Being tested
Mosunetuzumab Intravenous (IV), Mosunetuzumab Subcutaneous (SC), Polatuzumab Vedotin, Tocilizumab
Medical subject headings
Lymphoma, Large B-Cell, Diffuse

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Mosunetuzumab Intravenous (IV)Drug

    Participants in cohorts A and B will receive IV mosunetuzumab.

  • Mosunetuzumab Subcutaneous (SC)Drug

    Participants in Cohort C will receive SC mosunetuzumab.

  • Polatuzumab VedotinDrug

    Participants in Cohort C will receive IV polatuzumab vedotin.

  • TocilizumabDrug

    Participants will receive tocilizumab via IV as needed to manage severe cytokine release syndrome (CRS).

Study groups in NCT03677154
Study groupRoleWhat they receive
Consolidation Therapy (Cohort A)ExperimentalParticipants with a partial response to first-line chemotherapy will receive mosunetuzumab up to the recommended consolidation dose (RCD).
Receives: Drug: Mosunetuzumab Intravenous (IV); Drug: Tocilizumab
Elderly/Unfit Previously Untreated Monotherapy (Cohort B)ExperimentalElderly/unfit participants with previously untreated DLBCL will receive mosunetuzumab at the previously determined recommended phase II dose (RP2D).
Receives: Drug: Mosunetuzumab Intravenous (IV); Drug: Tocilizumab
Elderly/Unfit Previously Untreated Combination Therapy (Cohort C)ExperimentalElderly/unfit participants with previously untreated DLBCL will receive mosunetuzumab in combination with polatuzumab vedotin.
Receives: Drug: Mosunetuzumab Subcutaneous (SC); Drug: Polatuzumab Vedotin; Drug: Tocilizumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Percentage of Participants with Adverse Events

    Measured: Baseline through approximately 90 days after last study treatment

  2. Positron Emission Tomography-Computed Tomography (PET-CT) Complete Response (CR) Rate at Time of Primary Response Assessment (PRA) According to Lugano 2014 Response Criteria (Cohort A)

    Measured: 6-8 weeks after Cycle 8 Day 1 or the final dose of study treatment (cycle = 21 days)

  3. PET-CT Objective Response Rate (ORR) at PRA According to Lugano 2014 Response Criteria as Determined by the Investigator (Cohort B)

    Measured: 6-8 weeks after Cycle 8 Day 1 or the final dose of study treatment (cycle = 21 days)

  4. PET-CT ORR at PRA According to the Lugano 2014 Criteria as Determined by an Independent Review Committee (IRC) (Cohort C)

    Measured: 6-8 weeks after Cycle 8 Day 1 or the final dose of study treatment (cycle = 21 days)

Secondary outcomes (32)

  1. Maximum Serum Concentration (Cmax) of Mosunetuzumab IV

    Measured: At pre-defined intervals from Cycle 1 Day 1 through approximately 90 days after the last study treatment (cycle = 21 days)

  2. Minimum Serum Concentration (Cmin) of Mosunetuzumab IV

    Measured: At pre-defined intervals from Cycle 1 Day 1 through approximately 90 days after the last study treatment (cycle = 21 days)

  3. Area Under the Curve (AUC) of Mosunetuzumab IV

    Measured: At pre-defined intervals from Cycle 1 Day 1 through approximately 90 days after the last study treatment (cycle = 21 days)

  4. Clearance (CL) of Mosunetuzumab IV

    Measured: At pre-defined intervals from Cycle 1 Day 1 through approximately 90 days after the last study treatment (cycle = 21 days)

  5. Volume of Distribution at Steady State (Vss) of Mosunetuzumab IV

    Measured: At pre-defined intervals from Cycle 1 Day 1 through approximately 90 days after the last study treatment (cycle = 21 days)

  6. Maximum Serum Concentration (Cmax) of Mosunetuzumab SC

    Measured: At pre-defined intervals from Cycle 1 Day 1 through approximately 90 days after the last study treatment (cycle = 21 days)

  7. Time to Maximum Serum Concentration (Tmax) of Mosunetuzumab SC

    Measured: At pre-defined intervals from Cycle 1 Day 1 through approximately 90 days after the last study treatment (cycle = 21 days)

  8. Minimum Serum Concentration (Cmin) of Mosunetuzumab SC

    Measured: At pre-defined intervals from Cycle 1 Day 1 through approximately 90 days after the last study treatment (cycle = 21 days)

  9. Area Under the Curve (AUC) of Mosunetuzumab SC

    Measured: At pre-defined intervals from Cycle 1 Day 1 through approximately 90 days after the last study treatment (cycle = 21 days)

  10. Clearance (CL) of Mosunetuzumab SC

    Measured: At pre-defined intervals from Cycle 1 Day 1 through approximately 90 days after the last study treatment (cycle = 21 days)

  11. Volume of Distribution at Steady State (Vss) of Mosunetuzumab SC

    Measured: At pre-defined intervals from Cycle 1 Day 1 through approximately 90 days after the last study treatment (cycle = 21 days)

  12. Maximum Serum Concentration (Cmax) of Polatuzumab Vedotin IV

    Measured: At pre-defined intervals from Cycle 1 Day 1 through approximately 90 days after the last study treatment (cycle = 21 days)

  13. Minimum Serum Concentration (Cmin) of Polatuzumab Vedotin IV

    Measured: At pre-defined intervals from Cycle 1 Day 1 through approximately 90 days after the last study treatment (cycle = 21 days)

  14. Area Under the Curve (AUC) of Polatuzumab Vedotin IV

    Measured: At pre-defined intervals from Cycle 1 Day 1 through approximately 90 days after the last study treatment (cycle = 21 days)

  15. Clearance (CL) of Polatuzumab Vedotin IV

    Measured: At pre-defined intervals from Cycle 1 Day 1 through approximately 90 days after the last study treatment (cycle = 21 days)

  16. Volume of Distribution at Steady State (Vss) of Polatuzumab Vedotin IV

    Measured: At pre-defined intervals from Cycle 1 Day 1 through approximately 90 days after the last study treatment (cycle = 21 days)

  17. End of Infusion Concentration (Ceoi) of Polatuzumab Vedotin IV

    Measured: At pre-defined intervals from Cycle 1 Day 1 through approximately 90 days after the last study treatment (cycle = 21 days)

  18. Trough Concentration (Ctrough) of Polatuzumab Vedotin IV

    Measured: At pre-defined intervals from Cycle 1 Day 1 through approximately 90 days after the last study treatment (cycle = 21 days)

  19. PET-CT Rate According to the Lugano 2014 Criteria at PRA as Determined by the Investigator (Cohorts B and C) and IRC (Cohort C)

    Measured: 6-8 weeks after Cycle 8 Day 1 or the final dose of study treatment (cycle = 21 days)

  20. Objective Response Rate (ORR), Defined as the Proportion of Participants with a Complete Response (CR) or Partial Response (PR) at PRA as Determined by the Investigator (Cohorts A and C)

    Measured: Baseline through 2 years after PRA (up to a total of approximately 2.5 years)

  21. Best ORR (CR or PR at any time) During the Study Based on PET-CT and/or CT Scans as Determined by the Investigator (All Cohorts) and by IRC (Cohort C)

    Measured: Baseline through 2 years after PRA (up to a total of approximately 2.5 years)

  22. Duration of Response (DOR) as Determined by the Investigator (All Cohorts) and by IRC (Cohort C)

    Measured: From the first occurrence of a documented objective response to disease progression, relapse, or death, whichever occurs first (up to approximately 2.5 years)

  23. Duration of Confirmed Response (DOCR) as Determined by the Investigator (All Cohorts) and by IRC (Cohort C)

    Measured: From the first occurrence of a documented CR to disease progression or relapse, or death from any cause, whichever occurs first (up to approximately 2.5 years)

  24. Progression-Free Survival (PFS) as Determined by the Investigator (All Cohorts) and by IRC (Cohort C)

    Measured: From the first study treatment to the first occurrence of disease progression, relapse, or death, whichever occurs first (up to approximately 2.5 years)

  25. Overall Survival (OS)

    Measured: From the first study treatment to death from any cause

  26. Time to Deterioration in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) Physical Functioning and Fatigue (Cohorts B and C)

    Measured: From the first study treatment to the first occurrence of disease progression, relapse, initiation of new anti-lymphoma treatment, or death from any cause, whichever occurs first (up to approximately 2.5 years)

  27. Time to Deterioration in European Organization for Research and Treatment of Cancer Item Library (EORTC-IL17) Physical Functioning (Cohorts B and C)

    Measured: From the first study treatment to the first occurrence of disease progression, relapse, initiation of new anti-lymphoma treatment, or death from any cause, whichever occurs first (up to approximately 2.5 years)

  28. Time to Deterioration in the Functional Assessment of Cancer Therapy - Lymphoma (FACT-Lym) Subscale (Cohorts B and C)

    Measured: From the first study treatment to the first occurrence of disease progression, relapse, initiation of new anti-lymphoma treatment, or death from any cause, whichever occurs first (up to approximately 2.5 years)

  29. Proportion of Participants Achieving a Clinically Meaningful Improvement in Physical Functioning as Measured by EORTC QLQ-C30 (Cohorts B and C)

    Measured: From the first study treatment to the first occurrence of disease progression, relapse, initiation of new anti-lymphoma treatment, or death from any cause, whichever occurs first (up to approximately 2.5 years)

  30. Proportion of Participants Achieving a Clinically Meaningful Improvement in Physical Functioning as Measured by EORTC IL17 (Cohorts B and C)

    Measured: From the first study treatment to the first occurrence of disease progression, relapse, initiation of new anti-lymphoma treatment, or death from any cause, whichever occurs first (up to approximately 2.5 years)

  31. Anti-Drug Antibodies (ADAs) to Mosunetuzumab

    Measured: At pre-defined intervals from Cycle 1 Day 1 through approximately 90 days after the last study treatment (cycle = 21 days)

  32. Anti-Drug Antibodies (ADAs) to Polatuzumab Vedotin (Cohort C)

    Measured: At pre-defined intervals from Cycle 1 Day 1 through approximately 90 days after the last study treatment (cycle = 21 days)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted19 Sep 2018
  2. Study start23 May 2019
  3. Primary completion7 Aug 2025
  4. Study completion7 Aug 2025

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
188 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03677154
Sponsor's protocol ID
GO40554
Status last verified
Aug 2025
First submitted
11 Sep 2018
Last updated
21 Aug 2025
Results posted
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: For eligible studies, qualified researchers may request access to individual patient level clinical data. See Roche's commitment to transparency of clinical study information here: https://go.roche.com/data\_sharing

Publications

  • Olszewski AJ, Eradat HA, Avigdor A, Horowitz NA, McKinney MS, Lee ST, Bergua Burgues JM, Rodriguez Izquierdo A, Bastos-Oreiro M, Ganzel C, Kim TM, Jeon Y, Taszner M, Narkhede MS, Kim WS, Shin HJ, Woszczyk D, Goldschmidt N, Singh A, Wei MC, Wang J, Batlevi CL MD, PhD, Ead W, Janousek M, Sellam G Dr, Jurczak W. Mosunetuzumab and Polatuzumab Vedotin as First-line Treatment for Large B Cell Lymphoma in Older Unfit or Frail Patients. Blood. 2026 Oct 5:blood.2026035116. doi: 10.1182/blood.2026035116. Online ahead of print.

    PubMed 42832423

  • Duell J, Westin J. The future of immunotherapy for diffuse large B-cell lymphoma. Int J Cancer. 2025 Jan 15;156(2):251-261. doi: 10.1002/ijc.35156. Epub 2024 Sep 25.

    PubMed 39319495

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Mosunetuzumab Intravenous (IV), Mosunetuzumab Subcutaneous (SC) and Polatuzumab Vedotin in people with Diffuse Large B-cell Lymphoma, run by Hoffmann-La Roche at 32 sites in 6 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 12 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 21 Aug 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 32 sites in United States, Israel, South Korea, Spain, Poland and 1 more country. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percentage of Participants with Adverse Events (time frame: Baseline through approximately 90 days after last study treatment). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03677154, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Aug 2025.

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