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

NCT03677154 | Completed Phase 1 FDA Drug

• 1 other identifier: GO40554
• Study Type: interventional
• Target: 188
• Locations: 6 countries
• Sites: 32

Brief 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 subcutaneous mosunetuzumab in combination with polatuzumab vedotin IV in elderly/unfit participants with previously untreated DLBCL.

Conditions

Diffuse Large B-cell Lymphoma

Outcome Measures

Primary Outcomes (4)

• Percentage of Participants with Adverse Events

  Baseline through approximately 90 days after last study treatment

• 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)

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

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

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

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

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

Secondary Outcomes (32)

• Maximum Serum Concentration (Cmax) of Mosunetuzumab IV

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

• Minimum Serum Concentration (Cmin) of Mosunetuzumab IV

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

• Area Under the Curve (AUC) of Mosunetuzumab IV

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

• Clearance (CL) of Mosunetuzumab IV

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

• Volume of Distribution at Steady State (Vss) of Mosunetuzumab IV

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

Study Arms (3)

Consolidation Therapy (Cohort A)

EXPERIMENTAL

Participants with a partial response to first-line chemotherapy will receive mosunetuzumab up to the recommended consolidation dose (RCD).

Drug: Mosunetuzumab Intravenous (IV); Drug: Tocilizumab

Elderly/Unfit Previously Untreated Monotherapy (Cohort B)

EXPERIMENTAL

Elderly/unfit participants with previously untreated DLBCL will receive mosunetuzumab at the previously determined recommended phase II dose (RP2D).

Drug: Mosunetuzumab Intravenous (IV); Drug: Tocilizumab

Elderly/Unfit Previously Untreated Combination Therapy (Cohort C)

EXPERIMENTAL

Elderly/unfit participants with previously untreated DLBCL will receive mosunetuzumab in combination with polatuzumab vedotin.

Drug: Mosunetuzumab Subcutaneous (SC); Drug: Polatuzumab Vedotin; Drug: Tocilizumab

Interventions

Mosunetuzumab Intravenous (IV) DRUG

Participants in cohorts A and B will receive IV mosunetuzumab.

Consolidation Therapy (Cohort A); Elderly/Unfit Previously Untreated Monotherapy (Cohort B)

Mosunetuzumab Subcutaneous (SC) DRUG

Participants in Cohort C will receive SC mosunetuzumab.

Elderly/Unfit Previously Untreated Combination Therapy (Cohort C)

Polatuzumab Vedotin DRUG

Participants in Cohort C will receive IV polatuzumab vedotin.

Elderly/Unfit Previously Untreated Combination Therapy (Cohort C)

Tocilizumab DRUG

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

Consolidation Therapy (Cohort A); Elderly/Unfit Previously Untreated Combination Therapy (Cohort C); Elderly/Unfit Previously Untreated Monotherapy (Cohort B)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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

You may not qualify if:

• 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)
• 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:

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (32)

University of Alabama at Birmingham School of Medicine

Birmingham, Alabama, 352331912, United States

Location

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

Santa Monica, California, 90404-2023, United States

Location

Fort Wayne Medical Institute

Fort Wayne, Indiana, 46805, United States

Location

University of Maryland Medical Center

Baltimore, Maryland, 21201, United States

Location

Duke University

Durham, North Carolina, 27708-9963, United States

Location

Fox Chase Cancer Center

Philadelphia, Pennsylvania, 19111, United States

Location

Rhode Island Hospital

Providence, Rhode Island, 02903, United States

Location

Texas Oncology - Baylor Charles A. Sammons Cancer Center

Dallas, Texas, 75246, United States

Location

Soroka Medical Center

Beersheba, 8410101, Israel

Location

Rambam Medical Center

Haifa, 31096, Israel

Location

Carmel medical center

Haifa, 3436212, Israel

Location

Shaare Zedek Medical Center

Jerusalem, 9103102, Israel

Location

Hadassah Ein-Karem

Jerusalem, 91120, Israel

Location

Meir Medical Center

Kfar Saba, 4428164, Israel

Location

Sheba Medical Center

Ramat Gan, 5262100, Israel

Location

Uniwersyteckie Centrum Kliniczne

Gdansk, 80-214, Poland

Location

PRATIA MCM Kraków

Krakow, 30-727, Poland

Location

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

Lublin, 20-090, Poland

Location

Szpital Wojewodzki w Opolu

Opole, 45-372, Poland

Location

Pusan National University Hospital

Busan, 49241, South Korea

Location

Keimyung University Dongsan Hospital

Daegu, 41931, South Korea

Location

Samsung Medical Center

Seoul, (0)6351, South Korea

Location

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

Seoul, (0)7345, South Korea

Location

Seoul National University Hospital

Seoul, 03080, South Korea

Location

Severance Hospital, Yonsei University

Seoul, 03722, South Korea

Location

Hospital Universitario Virgen Macarena

Seville, Sevilla, 41071, Spain

Location

Hospital Universitario Vall d Hebron

Barcelona, 08035, Spain

Location

Institut Catala d Oncologia Hospitalet

Barcelona, 08908, Spain

Location

Hospital San Pedro de Alcantara

Cáceres, 10003, Spain

Location

Hospital General Universitario Gregorio Marañon

Madrid, 28007, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, 28041, Spain

Location

National Taiwan University Hospital

Taipei, 10002, Taiwan

Location

MeSH Terms

Conditions

Lymphoma, Large B-Cell, Diffuse

Interventions

polatuzumab vedotin; tocilizumab

Condition Hierarchy (Ancestors)

Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 11, 2018
• First Posted: September 19, 2018
• Study Start: May 23, 2019
• Primary Completion: August 7, 2025
• Study Completion: August 7, 2025
• Last Updated: August 21, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will share

Locations

IL (7); ES (6); PL (4); TW (1); US (8); KR (6)