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
B-cell Non-Hodgkin Lymphoma
About this trial
This is an interventional treatment trial for B-cell Non-Hodgkin Lymphoma
Eligibility Criteria
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
Sites / Locations
- University of Alabama Birmingham
- University of California; Moores Cancer Center
- University of California, Los Angeles (UCLA) - Hematology/Oncology Santa Monica
- Banner MD Anderson Cancer Center
- Georgetown University Medical Center
- University of Miami Miller School of Medicine
- University of Kansas Cancer Center
- Dana-Farber Cancer Institute
- University of Michigan
- Mayo Clinic Cancer Center
- Rhode Island Hospital
- Vanderbilt University Medical Center
- The University of Texas MD Anderson Cancer Center
- Scott and White Hospital; Cancer Center
- Medical College of Wisconsin, Inc.
- Uniklinikum Salzburg, LKH; Univ.Klinik f. Innere Medizin III der PMU
- LKH Steyr
- Medizinische Universität Wien, Allgemeines Krankenhaus der Stadt Wien
- Hanusch-Krankenhaus
- CHU Henri Mondor; Service d'Oncologie Medicale
- Centre Leon Berard
- Hôpital Saint-Louis
- Centre Henri Becquerel- Centre de Lutte Contre le Cancer
- Gustave Roussy
- Pusan National University Yangsan Hospital
- Seoul National University Hospital
- Asan Medical Center
- Samsung Medical Center
- Maria Sklodowska-Curie Memorial Cancer Centre
- Ma?opolskie Centrum Medyczne
- Wojewodzki Szpital Specjalistyczny im. Janusza Korczaka
- Instytut Hematologii i Transfuzjologii; Klinika Zaburze? Hemostazy i Chorób Wewn?trznych
- Katedra i Klinika Hematologii; Nowotworów Krwi i Transplantacji Szpiku
- Institut Catala d?Oncologia Hospital Germans Trias i Pujol
- Clinica Universidad de Navarra
- Hospital Universitario Virgen Macarena
- Hospital de la Santa Creu i Sant Pau
- Hospital San Pedro de Alcantara; Servicio de Hematología
- Hospital General Universitario Gregorio Marañon
- Hospital Universitario La Paz
- Hospital Universitario 12 de Octubre
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm 6
Experimental
Experimental
Experimental
Experimental
Active Comparator
Experimental
Phase Ib: Mosunetuzumab (M)-CHOP Dose Finding
Phase Ib: M-CHP-Pola Dose-Finding
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 II: M-CHOP 1L DLBCL
Participants will receive M-CHOP up to the phase II recommended dose (RP2D).
Participants will receive M-CHP-Pola up to the RP2D.
Participants with 1L DLBCL will receive mosunetuzumab at the RP2D in combination with CHOP.
Participants with 1L DLBCL will receive M-CHP-Pola at a dose determined in the dose finding stage.
Participants with 1L DLBCL will receive R-CHP-Pola at a dose determined in the dose finding stage.
Participants with 1L DLBCL will receive M-CHOP at a dose determined in the dose finding stage.