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

Purpose

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).

Condition

  • B-cell Non-Hodgkin Lymphoma

Eligibility

Eligible Ages
Over 18 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

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 Design

Phase
Phase 1/Phase 2
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
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: Rituxumab
    Participants will receive rituxumab 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.
Experimental
Phase II: M-CHOP 1L DLBCL
Participants with 1L DLBCL will receive M-CHOP at a dose determined in the dose finding stage.
  • 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.

More Details

Status
Active, not recruiting
Sponsor
Hoffmann-La Roche

Study Contact