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

NCT03677141 | Completed Phase 1 Results FDA Drug

• 2 other identifiers: GO405152018-001039-29
• Study Type: interventional
• Target: 117
• Locations: 6 countries
• Sites: 41

Brief Summary

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).

Conditions

B-cell Non-Hodgkin Lymphoma

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (16)

• 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)

  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)

  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)

  Up to approximately 50 months

• Duration of Response (DOR) as Determined by the Investigator (Phase II)

  Up to approximately 50 months

Study Arms (6)

Phase Ib: Mosunetuzumab (M)-CHOP Dose Finding

EXPERIMENTAL

Participants will receive M-CHOP up to the phase II recommended dose (RP2D).

Drug: Mosunetuzumab; Drug: Polatuzumab Vedotin; Drug: Cyclophosphamide; Drug: Doxorubicin; Drug: Vincristine; Drug: Prednisone; Drug: Tocilizumab

Phase Ib: M-CHP-Pola Dose-Finding

EXPERIMENTAL

Participants will receive M-CHP-Pola up to the RP2D.

Drug: Mosunetuzumab; Drug: Polatuzumab Vedotin; Drug: Cyclophosphamide; Drug: Doxorubicin; Drug: Prednisone; Drug: Tocilizumab

Phase II: M-CHOP Previously Untreated (1L) DLBCL Safety Cohort

EXPERIMENTAL

Participants with 1L DLBCL will receive mosunetuzumab at the RP2D in combination with CHOP.

Drug: Mosunetuzumab; Drug: Cyclophosphamide; Drug: Doxorubicin; Drug: Vincristine; Drug: Prednisone; Drug: Tocilizumab

Phase II: M-CHP-Pola 1L DLBCL

EXPERIMENTAL

Participants with 1L DLBCL will receive M-CHP-Pola at a dose determined in the dose finding stage.

Drug: Mosunetuzumab; Drug: Polatuzumab Vedotin; Drug: Cyclophosphamide; Drug: Doxorubicin; Drug: Prednisone; Drug: Tocilizumab

Phase II: Rituxumab (R)-CHP-Pola 1L DLBCL

ACTIVE COMPARATOR

Participants with 1L DLBCL will receive R-CHP-Pola at a dose determined in the dose finding stage.

Drug: Polatuzumab Vedotin; Drug: Rituxumab; Drug: Cyclophosphamide; Drug: Doxorubicin; Drug: Prednisone

Phase II: M-CHOP 1L DLBCL

EXPERIMENTAL

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; Drug: Cyclophosphamide; Drug: Doxorubicin; Drug: Vincristine; Drug: Prednisone; Drug: Tocilizumab

Interventions

Mosunetuzumab DRUG

Participants will receive intravenous (IV) mosunetuzumab.

Phase II: M-CHOP 1L DLBCL; Phase II: M-CHOP Previously Untreated (1L) DLBCL Safety Cohort; Phase II: M-CHP-Pola 1L DLBCL; Phase Ib: M-CHP-Pola Dose-Finding; Phase Ib: Mosunetuzumab (M)-CHOP Dose Finding

Polatuzumab Vedotin DRUG

Participants will receive polatuzumab vedotin via IV.

Phase II: M-CHP-Pola 1L DLBCL; Phase II: Rituxumab (R)-CHP-Pola 1L DLBCL; Phase Ib: M-CHP-Pola Dose-Finding; Phase Ib: Mosunetuzumab (M)-CHOP Dose Finding

Rituxumab DRUG

Participants will receive rituxumab via IV.

Phase II: Rituxumab (R)-CHP-Pola 1L DLBCL

Cyclophosphamide DRUG

Participants will receive cyclophosphamide via IV.

Phase II: M-CHOP 1L DLBCL; Phase II: M-CHOP Previously Untreated (1L) DLBCL Safety Cohort; Phase II: M-CHP-Pola 1L DLBCL; Phase II: Rituxumab (R)-CHP-Pola 1L DLBCL; Phase Ib: M-CHP-Pola Dose-Finding; Phase Ib: Mosunetuzumab (M)-CHOP Dose Finding

Doxorubicin DRUG

Participants will receive doxorubicin via IV.

Phase II: M-CHOP 1L DLBCL; Phase II: M-CHOP Previously Untreated (1L) DLBCL Safety Cohort; Phase II: M-CHP-Pola 1L DLBCL; Phase II: Rituxumab (R)-CHP-Pola 1L DLBCL; Phase Ib: M-CHP-Pola Dose-Finding; Phase Ib: Mosunetuzumab (M)-CHOP Dose Finding

Vincristine DRUG

Participants will receive vincristine via IV.

Phase II: M-CHOP 1L DLBCL; Phase II: M-CHOP Previously Untreated (1L) DLBCL Safety Cohort; Phase Ib: Mosunetuzumab (M)-CHOP Dose Finding

Prednisone DRUG

Participants will receive oral prednisone.

Phase II: M-CHOP 1L DLBCL; Phase II: M-CHOP Previously Untreated (1L) DLBCL Safety Cohort; Phase II: M-CHP-Pola 1L DLBCL; Phase II: Rituxumab (R)-CHP-Pola 1L DLBCL; Phase Ib: M-CHP-Pola Dose-Finding; Phase Ib: Mosunetuzumab (M)-CHOP Dose Finding

Tocilizumab DRUG

Participants will receive tocilizumab via IV.

Phase II: M-CHOP 1L DLBCL; Phase II: M-CHOP Previously Untreated (1L) DLBCL Safety Cohort; Phase II: M-CHP-Pola 1L DLBCL; Phase Ib: M-CHP-Pola Dose-Finding; Phase Ib: Mosunetuzumab (M)-CHOP Dose Finding

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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (41)

University of Alabama Birmingham

Birmingham, Alabama, 35233, United States

Location

Banner MD Anderson Cancer Center

Gilbert, Arizona, 85234, United States

Location

University of California; Moores Cancer Center

La Jolla, California, 92093, United States

Location

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

Santa Monica, California, 90404-2023, United States

Location

Georgetown University Medical Center

Washington D.C., District of Columbia, 20007, United States

Location

University of Miami Miller School of Medicine

Miami, Florida, 33136, United States

Location

University of Kansas Cancer Center

Westwood, Kansas, 66205, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

Mayo Clinic Cancer Center

Rochester, Minnesota, 55905, United States

Location

Rhode Island Hospital

Providence, Rhode Island, 02903-4923, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

The University of Texas MD Anderson Cancer Center

Houston, Texas, 77030-4009, United States

Location

Scott and White Hospital; Cancer Center

Temple, Texas, 76508, United States

Location

Medical College of Wisconsin, Inc.

Milwaukee, Wisconsin, 53226-3596, United States

Location

Uniklinikum Salzburg, LKH; Univ.Klinik f. Innere Medizin III der PMU

Salzburg, 5020, Austria

Location

LKH Steyr

Steyr, 4400, Austria

Location

Medizinische Universität Wien, Allgemeines Krankenhaus der Stadt Wien

Vienna, 1090, Austria

Location

Hanusch-Krankenhaus

Vienna, 1140, Austria

Location

CHU Henri Mondor; Service d'Oncologie Medicale

Créteil, 94010, France

Location

Centre Leon Berard

Lyon, 69008, France

Location

Hôpital Saint-Louis

Paris, 75475, France

Location

Centre Henri Becquerel- Centre de Lutte Contre le Cancer

Saint-Herblain, 44805, France

Location

Gustave Roussy

Villejuif, 94805, France

Location

Maria Sklodowska-Curie Memorial Cancer Centre

Gliwice, 44-102, Poland

Location

Ma?opolskie Centrum Medyczne

Krakow, 30-501, Poland

Location

Wojewodzki Szpital Specjalistyczny im. Janusza Korczaka

Słupsk, 76-200, Poland

Location

Instytut Hematologii i Transfuzjologii; Klinika Zaburze? Hemostazy i Chorób Wewn?trznych

Warsaw, 02-776, Poland

Location

Katedra i Klinika Hematologii; Nowotworów Krwi i Transplantacji Szpiku

Wroc?aw, Poland

Location

Pusan National University Yangsan Hospital

Gyeongsangnam-do, 50612, South Korea

Location

Seoul National University Hospital

Seoul, 03080, South Korea

Location

Asan Medical Center

Seoul, 05505, South Korea

Location

Samsung Medical Center

Seoul, 06351, South Korea

Location

Institut Catala d?Oncologia Hospital Germans Trias i Pujol

Badalona, Barcelona, 08916, Spain

Location

Clinica Universidad de Navarra

Pamplona, Navarre, 31008, Spain

Location

Hospital Universitario Virgen Macarena

Seville, Sevilla, 41071, Spain

Location

Hospital de la Santa Creu i Sant Pau

Barcelona, 8041, Spain

Location

Hospital San Pedro de Alcantara; Servicio de Hematología

Cáceres, 10003, Spain

Location

Hospital General Universitario Gregorio Marañon

Madrid, 28007, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, 28041, Spain

Location

Hospital Universitario La Paz

Madrid, 28046, Spain

Location

Related Publications (2)

• Westin J, Phillips TJ, Mehta A, Hoffmann MS, Gonzalez-Barca E, Thieblemont C, Bastos-Oreiro M, Greil R, Giebel S, Wei MC, Wang J, Bucher R, Sit J, Penuel E, Purev E, Yee DL, Bergua-Burgues JM. Mosunetuzumab plus Pola-CHP compared with Pola-R-CHP in previously untreated DLBCL: final results from a phase 2 study. Blood Adv. 2025 May 27;9(10):2461-2472. doi: 10.1182/bloodadvances.2024014907.

  PMID: 39908481 DERIVED

• Olszewski AJ, Phillips TJ, Hoffmann MS, Armand P, Kim TM, Yoon DH, Mehta A, Greil R, Westin J, Lossos IS, Munoz JL, Sit J, Wei MC, Yang A, Chen V, Purev E, Yee DL, Jaeger U. Mosunetuzumab in combination with CHOP in previously untreated DLBCL: safety and efficacy results from a phase 2 study. Blood Adv. 2023 Oct 24;7(20):6055-6065. doi: 10.1182/bloodadvances.2023010840.

  PMID: 37581593 DERIVED

MeSH Terms

Conditions

Lymphoma, B-Cell

Interventions

polatuzumab vedotin; Cyclophosphamide; Doxorubicin; Vincristine; Prednisone; tocilizumab

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines; Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds

Results Point of Contact

• Title: Medical Communications
• Organization: Hoffmann-La Roche

genentech@druginfo.com

1-800-821-8590

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

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: March 8, 2019
• Primary Completion: October 12, 2023
• Study Completion: October 12, 2023
• Last Updated: December 18, 2024
• Results First Posted: December 18, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will share

Locations

US (15); KR (4); FR (5); AU (4); PL (5); ES (8)