A Phase Ib/II Study Investigating the Safety, Tolerability, Pharmacokinetics, and Efficacy of Mosunetuzumab (BTCT4465A) in Combination With CHOP or CHP-Polatuzumab Vedotin in Participants With B-Cell Non-Hodgkin Lymphoma

A Phase Ib/II, Open-Label, Multicenter, Randomized, Controlled Study Investigating the Safety, Tolerability, Pharmacokinetics, and Efficacy of Mosunetuzumab (BTCT4465A) in Combination With CHOP or CHP-Polatuzumab Vedotin in Patients With B-Cell Non-Hodgkin Lymphoma

This study will evaluate the safety, pharmacokinetics, and preliminary efficacy of mosunetuzumab in combination with cyclophosphamide, doxorubicin, vincristine, and prednisone (M-CHOP) and, subsequently, in combination with cyclophosphamide, doxorubicin, and prednisone (CHP) plus polatuzumab vedotin (CHP-pola) in participants with relapsed or refractory (R/R) B-cell non-Hodgkin lymphoma (NHL), and in previously untreated participants with diffuse large B-cell lymphoma (DLBCL).

Study Overview

• Status: Completed
• Conditions: B-cell Non-Hodgkin Lymphoma
• Intervention / Treatment: Drug: Mosunetuzumab; Drug: Polatuzumab Vedotin; Drug: Cyclophosphamide; Drug: Doxorubicin; Drug: Vincristine; Drug: Prednisone; Drug: Tocilizumab; Drug: Rituxumab

• Study Type: Interventional
• Enrollment (Actual): 117
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Austria
  • Salzburg, Austria, 5020
    • Uniklinikum Salzburg, LKH; Univ.Klinik f. Innere Medizin III der PMU
  • Steyr, Austria, 4400
    • LKH Steyr
  • Wien, Austria, 1140
    • Hanusch-Krankenhaus
  • Wien, Austria, 1090
    • Medizinische Universität Wien, Allgemeines Krankenhaus der Stadt Wien
• France
  • Creteil, France, 94010
    • CHU Henri Mondor; Service d'Oncologie Medicale
  • Lyon, France, 69008
    • Centre Leon Berard
  • Paris, France, 75475
    • Hôpital Saint-Louis
  • Saint Herblain, France, 44805
    • Centre Henri Becquerel- Centre de Lutte Contre le Cancer
  • Villejuif, France, 94805
    • Gustave Roussy
• Korea, Republic of
  • Gyeongsangnam-do, Korea, Republic of, 50612
    • Pusan National University Yangsan Hospital
  • Seoul, Korea, Republic of, 03080
    • Seoul National University Hospital
  • Seoul, Korea, Republic of, 05505
    • Asan Medical Center
  • Seoul, Korea, Republic of, 06351
    • Samsung Medical Center
• Poland
  • Gliwice, Poland, 44-102
    • Maria Sklodowska-Curie Memorial Cancer Centre
  • Kraków, Poland, 30-501
    • Ma?opolskie Centrum Medyczne
  • Slupsk, Poland, 76-200
    • Wojewodzki Szpital Specjalistyczny im. Janusza Korczaka
  • Warsaw, Poland, 02-776
    • Instytut Hematologii i Transfuzjologii; Klinika Zaburze? Hemostazy i Chorób Wewn?trznych
  • Wroc?aw, Poland
    • Katedra i Klinika Hematologii; Nowotworów Krwi i Transplantacji Szpiku
• Spain
  • Barcelona, Spain, 8041
    • Hospital De La Santa Creu I Sant Pau
  • Caceres, Spain, 10003
    • Hospital San Pedro de Alcantara; Servicio de Hematología
  • Madrid, Spain, 28041
    • Hospital Universitario 12 de Octubre
  • Madrid, Spain, 28046
    • Hospital Universitario La Paz
  • Madrid, Spain, 28007
    • Hospital General Universitario Gregorio Marañón
  • Barcelona
    • Badalona, Barcelona, Spain, 08916
      • Institut Catala d?Oncologia Hospital Germans Trias i Pujol
  • Navarra
    • Pamplona, Navarra, Spain, 31008
      • Clinica Universidad de Navarra
  • Sevilla
    • Seville, Sevilla, Spain, 41071
      • Hospital Universitario Virgen Macarena
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • University of Alabama Birmingham
  • Arizona
    • Gilbert, Arizona, United States, 85234
      • Banner MD Anderson Cancer Center
  • California
    • La Jolla, California, United States, 92093
      • University of California; Moores Cancer Center
    • Santa Monica, California, United States, 90404-2023
      • University of California, Los Angeles (UCLA) - Hematology/Oncology Santa Monica
  • District of Columbia
    • Washington, District of Columbia, United States, 20007
      • Georgetown University Medical Center
  • Florida
    • Miami, Florida, United States, 33136
      • University of Miami Miller School of Medicine
  • Kansas
    • Westwood, Kansas, United States, 66205
      • University of Kansas Cancer Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Dana-Farber Cancer Institute
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic Cancer Center
  • Rhode Island
    • Providence, Rhode Island, United States, 02903-4923
      • Rhode Island Hospital
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University Medical Center
  • Texas
    • Houston, Texas, United States, 77030-4009
      • The University of Texas MD Anderson Cancer Center
    • Temple, Texas, United States, 76508
      • Scott and White Hospital; Cancer Center
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226-3596
      • Medical College of Wisconsin, Inc.

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria for Phase Ib and Phase II Portions

• 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
• Eastern Cooperative Oncology Group Performance Status of 0, 1, or 2
• Adequate hematologic function

Inclusion Criteria for Phase Ib Portion

Participants must also meet the following criteria for study entry into the Phase Ib portion:

• Histologically confirmed B-cell NHL according to the World Health Organization (WHO) 2016 classification expected to express the cluster of differentiation-20 (CD20) antigen
• Relapsed or refractory (R/R) B-cell NHL after at least one prior systemic lymphoma therapy
• Treatment with at least one prior CD20-directed therapy
• Group B only: no prior treatment with polatuzumab vedotin

Inclusion Criteria for Phase II Portion

Participants must also meet the following criteria for study entry in the Phase II portion:

• Previously untreated, histologically confirmed DLBCL according to WHO 2016 classification
• International Prognostic Index (IPI) score of 2-5

Exclusion Criteria

• Prior treatment with mosunetuzumab
• Prior allogenic stem-cell transplant
• Current Grade >1 peripheral neuropathy
• Participants with 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)
• Prior solid organ transplantation
• History of autoimmune disease
• Current or past history of central nervous system (CNS) lymphoma
• Current or past history of CNS disease, such as stroke, epilepsy, CNS vasculitis, or neurodegenerative disease
• Significant cardiovascular disease or pulmonary disease
• Clinically significant history of liver disease
• Recent major surgery within 4 weeks before the start of C1D1, other than superficial lymph node biopsies for diagnosis

Exclusion Criteria for Phase Ib Portion

Participants who also meet any of the following criteria will be excluded from study entry in the Phase Ib portion:

• Prior treatment with chemotherapy, immunotherapy, and biologic therapy 4 weeks prior to C1D1
• Prior treatment with radiotherapy within 2 weeks prior to C1D1
• Adverse events from prior anti-cancer therapy resolved to ≤Grade 1 (with the exception of alopecia and anorexia)
• Prior treatment with >250 mg/m^2 doxorubicin (or equivalent anthracycline dose)

Exclusion Criteria for Phase II Portion

Participants who also meet any of the following criteria will be excluded from study entry in the Phase II portion:

• Participants with transformed lymphoma
• Prior therapy for B-cell NHL

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

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Phase Ib: Mosunetuzumab (M)-CHOP Dose Finding; Participants will receive M-CHOP up to the phase II recommended dose (RP2D).	Drug: Mosunetuzumab; Participants will receive intravenous (IV) mosunetuzumab.; Drug: Polatuzumab Vedotin; Participants will receive polatuzumab vedotin via IV.; Drug: Cyclophosphamide; Participants will receive cyclophosphamide via IV.; Drug: Doxorubicin; Participants will receive doxorubicin via IV.; Drug: Vincristine; Participants will receive vincristine via IV.; Drug: Prednisone; Participants will receive oral prednisone.; Drug: Tocilizumab; Participants will receive tocilizumab via IV.
Experimental: Phase Ib: M-CHP-Pola Dose-Finding; Participants will receive M-CHP-Pola up to the RP2D.	Drug: Mosunetuzumab; Participants will receive intravenous (IV) mosunetuzumab.; Drug: Polatuzumab Vedotin; Participants will receive polatuzumab vedotin via IV.; Drug: Cyclophosphamide; Participants will receive cyclophosphamide via IV.; Drug: Doxorubicin; Participants will receive doxorubicin via IV.; Drug: Prednisone; Participants will receive oral prednisone.; Drug: Tocilizumab; Participants will receive tocilizumab via IV.
Experimental: Phase II: M-CHOP Previously Untreated (1L) DLBCL Safety Cohort; Participants with 1L DLBCL will receive mosunetuzumab at the RP2D in combination with CHOP.	Drug: Mosunetuzumab; Participants will receive intravenous (IV) mosunetuzumab.; Drug: Cyclophosphamide; Participants will receive cyclophosphamide via IV.; Drug: Doxorubicin; Participants will receive doxorubicin via IV.; Drug: Vincristine; Participants will receive vincristine via IV.; Drug: Prednisone; Participants will receive oral prednisone.; Drug: Tocilizumab; Participants will receive tocilizumab via IV.
Experimental: Phase II: M-CHP-Pola 1L DLBCL; Participants with 1L DLBCL will receive M-CHP-Pola at a dose determined in the dose finding stage.	Drug: Mosunetuzumab; Participants will receive intravenous (IV) mosunetuzumab.; Drug: Polatuzumab Vedotin; Participants will receive polatuzumab vedotin via IV.; Drug: Cyclophosphamide; Participants will receive cyclophosphamide via IV.; Drug: Doxorubicin; Participants will receive doxorubicin via IV.; Drug: Prednisone; Participants will receive oral prednisone.; Drug: Tocilizumab; Participants will receive tocilizumab via IV.
Active Comparator: Phase II: Rituxumab (R)-CHP-Pola 1L DLBCL; Participants with 1L DLBCL will receive R-CHP-Pola at a dose determined in the dose finding stage.	Drug: Polatuzumab Vedotin; Participants will receive polatuzumab vedotin via IV.; Drug: Cyclophosphamide; Participants will receive cyclophosphamide via IV.; Drug: Doxorubicin; Participants will receive doxorubicin via IV.; Drug: Prednisone; Participants will receive oral prednisone.; Drug: Rituxumab; Participants will receive rituxumab via IV.
Experimental: Phase II: M-CHOP 1L DLBCL; Participants with 1L DLBCL will receive M-CHOP at a dose determined in the dose finding stage. NOTE: No participants were enrolled to this arm.	Drug: Mosunetuzumab; Participants will receive intravenous (IV) mosunetuzumab.; Drug: Cyclophosphamide; Participants will receive cyclophosphamide via IV.; Drug: Doxorubicin; Participants will receive doxorubicin via IV.; Drug: Vincristine; Participants will receive vincristine via IV.; Drug: Prednisone; Participants will receive oral prednisone.; Drug: Tocilizumab; Participants will receive tocilizumab via IV.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complete Response (CR) Rate at the Time of Primary Response Assessment (PRA) Based on Positron Emission Tomography - Computed Tomography (PET-CT) as Determined by Independent Review Committee (IRC)	The CR rate was defined as the percentage of participants with CR. Assessments were made according to the Lugano 2014 Response Criteria.	6-8 weeks after either C6D1 or last dose of study treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
CR Rate at PRA Based on CT Only as Determined by the Investigator (Phase II)		6-8 weeks after C6D1 or last dose of study treatment
Overall Response Rate (ORR) at PRA Based on PET-CT as Determined by the Investigator (Phase II)	ORR is defined as a CR or PR at the time of primary assessment based on PET-CT, as determined by the investigator.	6-8 weeks after C6D1 or last dose of study treatment
ORR at PRA Based on CT Only as Determined by the Investigator (Phase II)	ORR is defined as a CR or PR at the time of primary assessment based on CT only, as determined by the investigator.	6-8 weeks after C6D1 or last dose of study treatment
Best ORR Based on PET-CT and/or CT Scan as Determined by the Investigator (Phase II)	Best ORR was defined as CR or PR at any time on study and based on PET-CT or CT only as determined by the investigator.	Up to approximately 50 months
Duration of Response (DOR) as Determined by the Investigator (Phase II)	DOR is defined as the time from the first occurrence of a documented objective response to disease progression or relapse as determined by the investigator, or death from any cause, whichever occurs first. The range values (min-max) are based on censored observations (if a participant did not experience disease progression or death prior to the end of the trial DOR was censored on the date of the last tumor assessment).	Up to approximately 50 months
Progression-free Survival (PFS) as Determined by the Investigator (Phase II)	PFS is defined as the time from randomization to the first occurrence of disease progression or relapse as determined by the investigator, or death from any cause, whichever occurs first. The earliest contributing event to PFS is reported. The range (min-max) values are based on censored observations (participants without a baseline-evaluable tumor assessment were censored at the date of randomization or first study treatment, plus 1 day).	Up to approximately 50 months
PFS at 1 Year as Determined by the Investigator (Phase II)	PFS at 1 year is defined as the proportion of participants with disease progression or relapse as determined by the investigator, or death from any cause within 1 year of randomization.	1 year
Event-free Survival (EFS) as Determined by the Investigator (Phase II)	EFS is defined as the time from randomization to the first occurrence of disease progression or relapse, as determined by the investigator, initiation of new anti-lymphoma therapy (NALT), or death from any cause, whichever occurs first. The range values (min-max) are based on censored observations (if a participant did not experience disease progression or death prior to the end of the trial DOR was censored on the date of the last tumor assessment).	Up to 50 months
Time to Deterioration in Lymphoma Symptoms as Measured by the Functional Assessment of Cancer Therapy - Lymphoma (FACT-Lym) Subscale		C1D1 through follow-up period (to begin 2 years after PRA or at the time of study drug discontinuation)
Time to Deterioration in Physical Functioning and Fatigue as Measured by the European Organization for Research and Treatment of Cancer Quality of Life - Core 30 Questionnaire (EORTC QLQ-C30)		C1D1 through follow-up period (to begin 2 years after PRA or at the time of study drug discontinuation)
Polatuzumab Vedotin Serum Concentrations		C2D1, C6D1
Polatuzumab Vedotin Antibody-conjugated Monomethyl Auristatin E (acMMAE) Serum Concentrations		C1D1-C6D1
Polatuzumab Vedotin Unconjugated Mono-methyl Auristatin E (MMAE) Serum Concentrations		C1D1-C6D1
Mosunetuzumab Serum Concentrations		C1D1-C5D1
Baseline Prevalence and Incidence of Treatment Emergent Anti-drug Antibodies (ADA) to Mosunetuzumab	Participants are considered to have treatment-induced ADA responses if they are ADA negative or missing data at baseline and then develop an ADA response following study drug administration. Participants are considered to have treatment-enhanced ADA responses if they are ADA positive at baseline and the titer of one or more post baseline samples is at least 4-fold greater than the titer of the baseline sample. Patients are considered to be negative for ADAs if they are ADA negative at all timepoints or if they are ADA positive at baseline but do not have any post-baseline samples with a titer that is at least 4-fold greater than the titer of the baseline sample (treatment unaffected).	Cycles 1, 2, 6, 16, and at early discontinuation visit or at PRA (6-8 weeks after either C6D1 or last dose of study treatment)
Baseline Prevalence and Incidence of Treatment Emergent ADA to Polatuzumab Vedotin	Participants are considered to have treatment-induced ADA responses if they are ADA negative or missing data at baseline and then develop an ADA response following study drug administration. Participants are considered to have treatment-enhanced ADA responses if they are ADA positive at baseline and the titer of one or more post baseline samples is at least 4-fold greater than the titer of the baseline sample. Patients are considered to be negative for ADAs if they are ADA negative at all timepoints or if they are ADA positive at baseline but do not have any post-baseline samples with a titer that is at least 4-fold greater than the titer of the baseline sample (treatment unaffected).	Cycles 1, 2, 6, and at early discontinuation visit or at PRA (6-8 weeks after either C6D1 or last dose of study treatment)

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): March 8, 2019
• Primary Completion (Actual): October 12, 2023
• Study Completion (Actual): October 12, 2023

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): March 25, 2025
• Last Update Submitted That Met QC Criteria: November 22, 2024
• Last Verified: November 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Lymphoma; Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Antibiotics, Antineoplastic; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Inflammatory Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Enzyme Inhibitors; Antirheumatic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Topoisomerase Inhibitors; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Antineoplastic Agents, Phytogenic; Topoisomerase II Inhibitors; Immunoconjugates; Polatuzumab vedotin; Prednisone; Cyclophosphamide; Doxorubicin; Vincristine
• Other Study ID Numbers: GO40515; 2018-001039-29 (EudraCT Number)

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