Purpose

This study will evaluate the safety, tolerability, pharmacokinetics, and efficacy of mosunetuzumab in combination with polatuzumab vedotin in participants with B-cell non-Hodgkin lymphoma (NHL). It will consist of a dose finding portion and two randomized cohorts for participants with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) or follicular lymphoma (FL).

Condition

Eligibility

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

Inclusion Criteria

  • ECOG PS of 0, 1, or 2
  • Histologically confirmed FL or DLBCL
  • Must have received at least one prior systemic treatment regimen containing an anti-CD20−directed therapy for DLBCL or FL
  • Relapsed to prior regimen(s) after having a documented history of response (complete response [CR], CR unconfirmed [CRu], or partial response [PR]) of >/= 6 months in duration from completion of regimen(s); or, refractory to any prior regimen, defined as no response to the prior therapy, or progression within 6 months of completion of the last dose of therapy
  • Measurable disease, defined as at least one bi-dimensionally measurable nodal lesion, defined as > 1.5 cm in its longest dimension, or at least one bi-dimensionally measurable extranodal lesion, defined as > 1.0 cm in its longest dimension
  • Adequate hematologic, renal, and hepatic function

Exclusion Criteria

  • Prior treatment with mosunetuzumab or other CD20-directed bispecific antibodies
  • Prior treatment with polatuzumab vedotin
  • Current > Grade 1 peripheral neuropathy
  • Prior use of any monoclonal antibody, radioimmunoconjugate or antibody-drug conjugate (ADC) within 4 weeks before first dose of study treatment
  • Treatment with any chemotherapeutic agent, or treatment with any other anti-cancer agent (investigational or otherwise) within 4 weeks or 5 half-lives of the drug, whichever is shorter, prior to first dose of study treatment
  • Treatment with radiotherapy within 2 weeks prior to the first dose of study treatment
  • Autologous stem-cell transplantation (SCT) within 100 days prior to first study treatment administration
  • Prior treatment with chimeric antigen receptor T-cell (CAR-T) therapy within 30 days before first study treatment administration
  • Prior allogeneic SCT
  • Prior solid organ transplantation
  • Patients with history of confirmed progressive multifocal leukoencephalopathy (PML)
  • Current or past history of central nervous system (CNS) lymphoma or CNS disease
  • History of autoimmune disease

Study Design

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

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Dose Finding
Participants will receive mosunetuzumab in combination with polatuzumab vedotin. Dose finding will be guided by the observed incidence of dose-limiting toxicities (DLTs) at each dose level.
  • Drug: Mosunetuzumab
    Participants will receive intravenous (IV) mosunetuzumab.
    Other names:
    • BTCT4465A
  • Drug: Polatuzumab vedotin
    Participants will receive IV polatuzumab vedotin.
  • Drug: Tocilizumab
    Participants will receive IV tocilizumab as needed.
Active Comparator
Bendamustine + Rituximab + Polatuzumab Vedotin
Participants with DLBCL randomized to this arm will receive bendamustine + rituxumab + polatuzumab vedotin.
  • Drug: Polatuzumab vedotin
    Participants will receive IV polatuzumab vedotin.
  • Drug: Rituximab
    Participants will receive IV rituxumab.
  • Drug: Bendamustine
    Participants will receive IV bendamustine.
Active Comparator
Rituxumab-Chemotherapy/Bendamustine + Obinutuzumab
Participants with FL randomized to this arm will receive investigator's choice of either rituximab + cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP), rituximab + cyclophosphamide, vincristine, and prednisone (R-CVP), or obinutuzumab + bendamustine followed by obinutuzumab maintenance.
  • Drug: Rituximab
    Participants will receive IV rituxumab.
  • Drug: Bendamustine
    Participants will receive IV bendamustine.
  • Drug: Obinutuzumab
    Participants will receive IV obinutuzumab.
  • Drug: Cyclophosphamide
    Participants will receive IV cyclophosphamide.
  • Drug: Doxorubicin
    Participants will receive IV doxorubicin.
  • Drug: Vincristine
    Participants will receive IV vincristine.
  • Drug: Prednisone
    Participants will receive oral prednisone.
Experimental
Mosunetuzumab FL
Participants with FL randomized to this arm will receive mosunetuzumab at the recommended Phase II dose (RP2D) as a single-agent.
  • Drug: Mosunetuzumab
    Participants will receive intravenous (IV) mosunetuzumab.
    Other names:
    • BTCT4465A
  • Drug: Tocilizumab
    Participants will receive IV tocilizumab as needed.
Experimental
Mosunetuzumab DLBCL
Participants with DLBCL randomized to this arm will receive mosunetuzumab at the RP2D as a single agent.
  • Drug: Mosunetuzumab
    Participants will receive intravenous (IV) mosunetuzumab.
    Other names:
    • BTCT4465A
  • Drug: Tocilizumab
    Participants will receive IV tocilizumab as needed.
Experimental
Mosunetuzumab + Polatuzumab Vedotin FL
Participants with FL randomized to this arm will receive mosunetuzumab at the RP2D in combination with polatuzumab vedotin.
  • Drug: Mosunetuzumab
    Participants will receive intravenous (IV) mosunetuzumab.
    Other names:
    • BTCT4465A
  • Drug: Polatuzumab vedotin
    Participants will receive IV polatuzumab vedotin.
  • Drug: Tocilizumab
    Participants will receive IV tocilizumab as needed.
Experimental
Mosunetuzumab + Polatuzumab Vedotin DLBCL
Participants with DLBCL randomized to this arm will receive mosunetuzumab at the RP2D in combination with polatuzumab vedotin.
  • Drug: Mosunetuzumab
    Participants will receive intravenous (IV) mosunetuzumab.
    Other names:
    • BTCT4465A
  • Drug: Polatuzumab vedotin
    Participants will receive IV polatuzumab vedotin.
  • Drug: Tocilizumab
    Participants will receive IV tocilizumab as needed.

Recruiting Locations

University of Alabama at Birmingham School of Medicine
Birmingham, Alabama 352331912

More Details

NCT ID
NCT03671018
Status
Recruiting
Sponsor
Hoffmann-La Roche

Study Contact

Reference Study ID Number: GO40516 www.roche.com/about_roche/roche_worldwide.htm
888-662-6728 (U.S. and Canada)
global.rochegenentechtrials@roche.com

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.