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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

Description:

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).

Related Conditions:
  • B-Cell Non-Hodgkin Lymphoma
  • Diffuse Large B-Cell Lymphoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: 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
  • Official Title: 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

Clinical Trial IDs

  • ORG STUDY ID: GO40515
  • SECONDARY ID: 2018-001039-29
  • NCT ID: NCT03677141

Conditions

  • B-cell Non-Hodgkin Lymphoma

Interventions

DrugSynonymsArms
MosunetuzumabPhase II: M-CHOP 1L DLBCL
Polatuzumab VedotinPhase II: M-CHP-Pola 1L DLBCL
RituxumabPhase II: Rituxumab (R)-CHP-Pola 1L DLBCL
CyclophosphamidePhase II: M-CHOP 1L DLBCL
DoxorubicinPhase II: M-CHOP 1L DLBCL
VincristinePhase II: M-CHOP 1L DLBCL
PrednisonePhase II: M-CHOP 1L DLBCL
TocilizumabPhase II: M-CHOP 1L DLBCL

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).

Trial Arms

NameTypeDescriptionInterventions
Phase Ib: Mosunetuzumab (M)-CHOP Dose FindingExperimentalParticipants will receive M-CHOP up to the phase II recommended dose (RP2D).
  • Mosunetuzumab
  • Polatuzumab Vedotin
  • Cyclophosphamide
  • Doxorubicin
  • Vincristine
  • Prednisone
  • Tocilizumab
Phase Ib: M-CHP-Pola Dose-FindingExperimentalParticipants will receive M-CHP-Pola up to the RP2D.
  • Mosunetuzumab
  • Polatuzumab Vedotin
  • Cyclophosphamide
  • Doxorubicin
  • Prednisone
  • Tocilizumab
Phase II: M-CHOP Previously Untreated (1L) DLBCL Safety CohortExperimentalParticipants with 1L DLBCL will receive mosunetuzumab at the RP2D in combination with CHOP.
  • Mosunetuzumab
  • Cyclophosphamide
  • Doxorubicin
  • Vincristine
  • Prednisone
  • Tocilizumab
Phase II: M-CHP-Pola 1L DLBCLExperimentalParticipants with 1L DLBCL will receive M-CHP-Pola at a dose determined in the dose finding stage.
  • Mosunetuzumab
  • Polatuzumab Vedotin
  • Cyclophosphamide
  • Doxorubicin
  • Prednisone
  • Tocilizumab
Phase II: Rituxumab (R)-CHP-Pola 1L DLBCLActive ComparatorParticipants with 1L DLBCL will receive R-CHP-Pola at a dose determined in the dose finding stage.
  • Polatuzumab Vedotin
  • Rituxumab
  • Cyclophosphamide
  • Doxorubicin
  • Prednisone
Phase II: M-CHOP 1L DLBCLExperimentalParticipants with 1L DLBCL will receive M-CHOP at a dose determined in the dose finding stage.
  • Mosunetuzumab
  • Cyclophosphamide
  • Doxorubicin
  • Vincristine
  • Prednisone
  • Tocilizumab

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 in 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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Percentage of Participants with Adverse Events (AE)
Time Frame:Baseline through approximately 90 days after the last study treatment
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Maximum Serum Concentration (Cmax) of Mosunetuzumab
Time Frame:At pre-defined intervals from Cycle 1, Day 1 through approximately 90 days after the last study treatment (cycle = 21 days)
Safety Issue:
Description:
Measure:Minimum Serum Concentration (Cmin) of Mosunetuzumab
Time Frame:At pre-defined intervals from Cycle 1, Day 1 through approximately 90 days after the last study treatment (cycle = 21 days)
Safety Issue:
Description:
Measure:Area Under the Curve (AUC) of Mosunetuzumab
Time Frame:At pre-defined intervals from Cycle 1, Day 1 through approximately 90 days after the last study treatment (cycle = 21 days)
Safety Issue:
Description:
Measure:Clearance (CL) of Mosunetuzumab
Time Frame:At pre-defined intervals from Cycle 1, Day 1 through approximately 90 days after the last study treatment (cycle = 21 days)
Safety Issue:
Description:
Measure:Volume of Distribution at Steady State (Vss) of Mosunetuzumab
Time Frame:At pre-defined intervals from Cycle 1, Day 1 through approximately 90 days after the last study treatment (cycle = 21 days)
Safety Issue:
Description:
Measure:Maximum Plasma Concentration (Cmax) of Polatuzumab Vedotin
Time Frame:At pre-defined intervals from Cycle 1, Day 1 through approximately 90 days after the last study treatment (cycle = 21 days)
Safety Issue:
Description:
Measure:Minimum Plasma Concentration (Cmin) of Polatuzumab Vedotin
Time Frame:At pre-defined intervals from Cycle 1, Day 1 through approximately 90 days after the last study treatment (cycle = 21 days)
Safety Issue:
Description:
Measure:AUC of Polatuzumab Vedotin
Time Frame:At pre-defined intervals from Cycle 1, Day 1 through approximately 90 days after the last study treatment (cycle = 21 days)
Safety Issue:
Description:
Measure:CL of Polatuzumab Vedotin
Time Frame:At pre-defined intervals from Cycle 1, Day 1 through approximately 90 days after the last study treatment (cycle = 21 days)
Safety Issue:
Description:
Measure:Vss of Polatuzumab Vedotin
Time Frame:At pre-defined intervals from Cycle 1, Day 1 through approximately 90 days after the last study treatment (cycle = 21 days)
Safety Issue:
Description:
Measure:Best Objective Response Rate (ORR), Defined as Complete Response (CR) or Partial Response (PR) at any Time on Study Based on PET-CT and/or CT scan as Assessed According to Lugano 2014 Response Criteria
Time Frame:Baseline through 2 years after partial response assessment (PRA) (up to a total of approximately 2.5 years)
Safety Issue:
Description:
Measure:Duration of Response (DOR)
Time Frame:From the first occurrence of a response to disease progression, relapse, or death, whichever comes first (up to approximately 2.5 years)
Safety Issue:
Description:
Measure:Anti-Drug Antibodies (ADAs) to Mosunetuzumab
Time Frame:At pre-defined intervals from Cycle 1, Day 1 through approximately 90 days after the last study treatment (cycle = 21 days)
Safety Issue:
Description:
Measure:ADAs to Polatuzumab Vedotin
Time Frame:At pre-defined intervals from Cycle 1, Day 1 through approximately 90 days after the last study treatment (cycle = 21 days)
Safety Issue:
Description:
Measure:Progression-Free Survival (PFS)
Time Frame:From randomization to the first occurrence of disease progression, relapse, or death from any cause, whichever occurs first (up to approximately 2.5 years)
Safety Issue:
Description:
Measure:PFS at 1 Year
Time Frame:Randomization to 1 Year
Safety Issue:
Description:
Measure:Event-Free Survival (EFS)
Time Frame:From randomization to the first occurrence of disease progression or relapse, initiation of new anti-lymphoma therapy (NALT), or death from any cause, whichever occurs first (up to approximately 2.5 years)
Safety Issue:
Description:
Measure:Time to Deterioration in the European Organization for Research and Treatment of Cancer Quality of Life - Core 30 Questionnaire (EORTC QLQ-C30) Physical Functioning and Fatigue
Time Frame:From baseline through follow-up (up to approximately 2.5 years)
Safety Issue:
Description:
Measure:Time to Deterioration in the Functional Assessment of Cancer Therapy - Lymphoma (FACT-Lym) Subscale
Time Frame:From baseline through follow-up (up to approximately 2.5 years)
Safety Issue:
Description:

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Hoffmann-La Roche

Last Updated

February 3, 2020