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 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.

Study Overview

• Status: Active, not recruiting
• Conditions: Diffuse Large B-cell Lymphoma
• Intervention / Treatment: Drug: Mosunetuzumab Intravenous (IV); Drug: Tocilizumab; Drug: Mosunetuzumab Subcutaneous (SC); Drug: Polatuzumab Vedotin

• Study Type: Interventional
• Enrollment (Estimated): 188
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Reference Study ID Number: GO40554 https://forpatients.roche.com/; Phone Number: 888-662-6728 (U.S. and Canada); Email: global.rochegenentechtrials@roche.com

Study Locations

• Israel
  • Beer Sheva, Israel, 8410101
    • Soroka Medical Center
  • Haifa, Israel, 3109601
    • Rambam Medical Center
  • Haifa, Israel, 3436212
    • Carmel Medical Center
  • Jerusalem, Israel, 9103102
    • Shaare Zedek Medical Center
  • Jerusalem, Israel, 9112001
    • Hadassah Ein-Karem; Clinical Pharmacology Unit
  • Kfar- Saba, Israel, 4428164
    • Meir Medical Center
  • Netanya, Israel, 4215000
    • Laniado Hospital-Sanz Medical Center
  • Petach Tikva, Israel, 4941492
    • Rabin Medical Center-Beilinson Campus
  • Ramat Gan, Israel, 5262100
    • Sheba Medical Center
  • Rehovot, Israel, 7610001
    • Kaplan Medical Center
  • Tel Aviv, Israel, 6423906
    • Tel Aviv Sourasky Medical Center; Pharmacy
• Korea, Republic of
  • Busan, Korea, Republic of, 602-739
    • Pusan National University Hospital
  • Daegu, Korea, Republic of, 41931
    • Keimyung University Dongsan Hospital
  • Incheon, Korea, Republic of, 21565
    • Gachon University Gil Medical Center
  • Seoul, Korea, Republic of, 03080
    • Seoul National University Hospital
  • Seoul, Korea, Republic of, 06351
    • Samsung Medical Center
  • Seoul, Korea, Republic of, 03722
    • Severance Hospital, Yonsei University
  • Seoul, Korea, Republic of, (0)7345
    • The Catholic University of Korea Yeouido St. Mary's Hospital; Hematology-Oncology
• Poland
  • Gdansk, Poland
    • Uniwersyteckie Centrum Kliniczne
  • Gdynia, Poland, 81-519
    • Szpitale Pomorskie Sp. z o. o.
  • Kraków, Poland, 30-727
    • Pratia MCM Krakow
  • Lublin, Poland, 20-090
    • Centrum Onkologii Ziemi Lubelskiej im. ?w. Jana z Dukli
  • Opole, Poland, 45-372
    • Szpital Wojewodzki w Opolu;Pododdz. Gastroenter., Pododdz. Hematologii
  • Warszawa, Poland, 02-776
    • Instytut Hematologii i Transfuzjologii; Klinika Hematologii
• Spain
  • Barcelona, Spain, 08035
    • Hospital Universitario Vall d Hebron
  • Caceres, Spain, 10003
    • Hospital San Pedro de Alcantara; Servicio de Hematología
  • Madrid, Spain, 28041
    • Hospital Universitario 12 de Octubre
  • Madrid, Spain, 28007
    • Hospital General Universitario Gregorio Maranon
  • Valencia, Spain, 46026
    • Hospital Universitari i Politecnic La Fe
  • Barcelona
    • Hospitalet de Llobregat, Barcelona, Spain, 08908
      • Institut Catala d Oncologia Hospitalet
  • Sevilla
    • Seville, Sevilla, Spain, 41071
      • Hospital Universitario Virgen Macarena
• Taiwan
  • New Taipei City, Taiwan, 23561
    • Taipei Medical University ?Shuang Ho Hospital
  • Tainan, Taiwan, 00704
    • National Cheng Kung University Hospital; Oncology
  • Tainan, Taiwan, 736
    • Chi-Mei Hospital, Liouying
  • Taipei, Taiwan, 10002
    • National Taiwan University Hospital
  • Taipei, Taiwan, 104
    • Mackay Memorial Hospital
  • Taipei City, Taiwan, 11217
    • Taipei Veterans General Hospital
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35249
      • University of Alabama at Birmingham School of Medicine
  • California
    • Santa Monica, California, United States, 90404-2023
      • University of California, Los Angeles (UCLA) - Hematology/Oncology Santa Monica
  • Florida
    • Miami, Florida, United States, 33176
      • Miami Cancer Institute of Baptist Health, Inc.
    • Miami, Florida, United States, 33136
      • University of Miami Sylvester Comprehensive Center
    • Tampa, Florida, United States, 33617
      • Moffitt Cancer Center Screening and Prevention
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Rush University Medical Center; Rush University Cancer Center
  • Indiana
    • Fort Wayne, Indiana, United States, 46805
      • Fort Wayne Medical Institute
  • Kentucky
    • Louisville, Kentucky, United States, 40207
      • Norton Medical Plaza II; Norton Cancer Institute
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • University of Maryland Medical Center
  • Michigan
    • Ann Arbor, Michigan, United States, 48109-0934
      • University of Michigan
  • New York
    • New York, New York, United States, 10065
      • Sloan Kettering Cancer Center
  • North Carolina
    • Durham, North Carolina, United States, 27708-9963
      • Duke University
  • Oregon
    • Portland, Oregon, United States, 97213
      • Providence Portland Medical Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19111
      • Fox Chase Cancer Center
  • Rhode Island
    • Providence, Rhode Island, United States, 02903-4923
      • Rhode Island Hospital
  • Texas
    • Dallas, Texas, United States, 75246
      • Texas Oncology - Baylor Charles A. Sammons Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria for All Cohorts

• 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

Inclusion Criteria Specific to Cohort A

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

Inclusion Criteria Specific to Cohorts B and C

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

Exclusion Criteria for All Cohorts

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

Exclusion Criteria Specific to Cohort A

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

Exclusion Criterion Specific to Cohorts B and C

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

Exclusion Criteria Specific to Cohort C

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

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: Consolidation Therapy (Cohort A); Participants with a partial response to first-line chemotherapy will receive mosunetuzumab up to the recommended consolidation dose (RCD).	Drug: Mosunetuzumab Intravenous (IV); Participants in cohorts A and B will receive IV mosunetuzumab.; Drug: Tocilizumab; Participants will receive tocilizumab via IV as needed to manage severe cytokine release syndrome (CRS).
Experimental: Elderly/Unfit Previously Untreated Monotherapy (Cohort B); Elderly/unfit participants with previously untreated DLBCL will receive mosunetuzumab at the previously determined recommended phase II dose (RP2D).	Drug: Mosunetuzumab Intravenous (IV); Participants in cohorts A and B will receive IV mosunetuzumab.; Drug: Tocilizumab; Participants will receive tocilizumab via IV as needed to manage severe cytokine release syndrome (CRS).
Experimental: Elderly/Unfit Previously Untreated Combination Therapy (Cohort C); Elderly/unfit participants with previously untreated DLBCL will receive mosunetuzumab in combination with polatuzumab vedotin.	Drug: Tocilizumab; Participants will receive tocilizumab via IV as needed to manage severe cytokine release syndrome (CRS).; Drug: Mosunetuzumab Subcutaneous (SC); Participants in Cohort C will receive SC mosunetuzumab.; Drug: Polatuzumab Vedotin; Participants in Cohort C will receive IV polatuzumab vedotin.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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 Outcome Measures

Outcome Measure	Time Frame
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)
Maximum Serum Concentration (Cmax) of Mosunetuzumab SC	At pre-defined intervals from Cycle 1 Day 1 through approximately 90 days after the last study treatment (cycle = 21 days)
Time to Maximum Serum Concentration (Tmax) of Mosunetuzumab SC	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 SC	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 SC	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 SC	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 SC	At pre-defined intervals from Cycle 1 Day 1 through approximately 90 days after the last study treatment (cycle = 21 days)
Maximum Serum Concentration (Cmax) of Polatuzumab Vedotin 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 Polatuzumab Vedotin 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 Polatuzumab Vedotin 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 Polatuzumab Vedotin 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 Polatuzumab Vedotin IV	At pre-defined intervals from Cycle 1 Day 1 through approximately 90 days after the last study treatment (cycle = 21 days)
End of Infusion Concentration (Ceoi) of Polatuzumab Vedotin IV	At pre-defined intervals from Cycle 1 Day 1 through approximately 90 days after the last study treatment (cycle = 21 days)
Trough Concentration (Ctrough) of Polatuzumab Vedotin IV	At pre-defined intervals from Cycle 1 Day 1 through approximately 90 days after the last study treatment (cycle = 21 days)
PET-CT Rate According to the Lugano 2014 Criteria at PRA as Determined by the Investigator (Cohorts B and C) and IRC (Cohort C)	6-8 weeks after Cycle 8 Day 1 or the final dose of study treatment (cycle = 21 days)
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)	Baseline through 2 years after PRA (up to a total of approximately 2.5 years)
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)	Baseline through 2 years after PRA (up to a total of approximately 2.5 years)
Duration of Response (DOR) as Determined by the Investigator (All Cohorts) and by IRC (Cohort C)	From the first occurrence of a documented objective response to disease progression, relapse, or death, whichever occurs first (up to approximately 2.5 years)
Duration of Confirmed Response (DOCR) as Determined by the Investigator (All Cohorts) and by IRC (Cohort C)	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)
Progression-Free Survival (PFS) as Determined by the Investigator (All Cohorts) and by IRC (Cohort C)	From the first study treatment to the first occurrence of disease progression, relapse, or death, whichever occurs first (up to approximately 2.5 years)
Overall Survival (OS)	From the first study treatment to death from any cause
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)	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)
Time to Deterioration in European Organization for Research and Treatment of Cancer Item Library (EORTC-IL17) Physical Functioning (Cohorts B and C)	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)
Time to Deterioration in the Functional Assessment of Cancer Therapy - Lymphoma (FACT-Lym) Subscale (Cohorts B and C)	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)
Proportion of Participants Achieving a Clinically Meaningful Improvement in Physical Functioning as Measured by EORTC QLQ-C30 (Cohorts B and C)	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)
Proportion of Participants Achieving a Clinically Meaningful Improvement in Physical Functioning as Measured by EORTC IL17 (Cohorts B and C)	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)
Anti-Drug Antibodies (ADAs) to Mosunetuzumab	At pre-defined intervals from Cycle 1 Day 1 through approximately 90 days after the last study treatment (cycle = 21 days)
Anti-Drug Antibodies (ADAs) to Polatuzumab Vedotin (Cohort C)	At pre-defined intervals from Cycle 1 Day 1 through approximately 90 days after the last study treatment (cycle = 21 days)

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche
• Investigators: Study Director: Clinical Trials, Hoffmann-La Roche

Study record dates

Study Major Dates

• Study Start (Actual): May 23, 2019
• Primary Completion (Actual): August 3, 2023
• Study Completion (Estimated): August 3, 2025

Study Registration Dates

• First Submitted: September 11, 2018
• First Submitted That Met QC Criteria: September 17, 2018
• First Posted (Actual): September 19, 2018

Study Record Updates

• Last Update Posted (Actual): April 12, 2024
• Last Update Submitted That Met QC Criteria: April 11, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma; Lymphoma, B-Cell; Lymphoma, Large B-Cell, Diffuse; Physiological Effects of Drugs; Immunologic Factors; Immunoconjugates; Polatuzumab vedotin
• Other Study ID Numbers: GO40554

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here (https://vivli.org/ourmember/roche/). For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm).

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No