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A Study to Evaluate the Safety and Efficacy of Mosunetuzumab (BTCT4465A) in Combination With Polatuzumab Vedotin in B-Cell Non-Hodgkin Lymphoma

NCT03671018

Description:

This study will evaluate the safety, tolerability, pharmacokinetics, and efficacy of mosunetuzumab in combination with polatuzumab vedotin in participants with diffuse large B-cell lymphoma (DLBCL) and in participants with follicular lymphoma (FL). It will consist of a dose finding portion followed by an expansion phase for second line or later (2L+) participants with relapsed or refractory (R/R) DLBCL and 2L+ R/R FL.

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

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Study to Evaluate the Safety and Efficacy of Mosunetuzumab (BTCT4465A) in Combination With Polatuzumab Vedotin in B-Cell Non-Hodgkin Lymphoma
  • Official Title: An Open-Label, Randomized, Multicenter, Phase Ib/II Trial Evaluating the Safety, Tolerability, Pharmacokinetics, and Efficacy of Mosunetuzumab (BTCT4465A) in Combination With Polatuzumab Vedotin in Patients With B-Cell Non-Hodgkin Lymphoma

Clinical Trial IDs

  • ORG STUDY ID: GO40516
  • SECONDARY ID: 2018-001141-13
  • NCT ID: NCT03671018

Conditions

  • B-cell Non-Hodgkin Lymphoma

Interventions

DrugSynonymsArms
MosunetuzumabBTCT4465ADose Finding
Polatuzumab vedotinBendamustine + Rituximab + Polatuzumab Vedotin
RituximabBendamustine + Rituximab + Polatuzumab Vedotin
BendamustineBendamustine + Rituximab + Polatuzumab Vedotin
TocilizumabBendamustine + Rituximab + Polatuzumab Vedotin

Purpose

This study will evaluate the safety, tolerability, pharmacokinetics, and efficacy of mosunetuzumab in combination with polatuzumab vedotin in participants with diffuse large B-cell lymphoma (DLBCL) and in participants with follicular lymphoma (FL). It will consist of a dose finding portion followed by an expansion phase for second line or later (2L+) participants with relapsed or refractory (R/R) DLBCL and 2L+ R/R FL.

Trial Arms

NameTypeDescriptionInterventions
Dose FindingExperimentalParticipants 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.
  • Mosunetuzumab
  • Polatuzumab vedotin
  • Tocilizumab
Bendamustine + Rituximab + Polatuzumab VedotinActive ComparatorParticipants with DLBCL randomized to this arm will receive bendamustine + rituxumab + polatuzumab vedotin.
  • Polatuzumab vedotin
  • Rituximab
  • Bendamustine
  • Tocilizumab
Mosunetuzumab DLBCLExperimentalParticipants with DLBCL randomized to this arm will receive mosunetuzumab at the RP2D as a single agent.
  • Mosunetuzumab
  • Tocilizumab
Expansion PhaseExperimentalParticipants with R/R FL and participants with R/R DLBCL will receive mosunetuzumab and polatuzumab vedotin at the RP2D.
  • Mosunetuzumab
  • Polatuzumab vedotin
  • Tocilizumab
Mosunetuzumab + Polatuzumab Vedotin DLBCLExperimentalParticipants with DLBCL randomized to this arm will receive mosunetuzumab + polatuzumab vedotin.
  • Mosunetuzumab
  • Polatuzumab vedotin
  • Tocilizumab

Eligibility Criteria

        Key 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

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

Primary Outcome Measures

Measure:Complete Response (CR) Rate Based on Positron Emission Tomography-Computed Tomography (PET-CT), as Assessed Using Standard Criteria for non-Hodgkin Lymphoma (NHL)
Time Frame:Cycle 8 completion (participants receiving mosunetuzumab), or 5-7 weeks after Cycle 6 (polatuzumab+bendamustine+rituximab participants) (Cycle = 21 days)
Safety Issue:
Description:

Secondary Outcome Measures

Measure:CR Rate Based on PET-CT, as Assessed Using Standard Criteria for NHL
Time Frame:Cycle 8 completion (participants receiving mosunetuzumab), or 5-7 weeks after Cycle 6 (polatuzumab+bendamustine+rituximab participants) (Cycle = 21 days)
Safety Issue:
Description:
Measure:CR Rate Based on CT Only, as Assessed Using Standard Criteria for NHL
Time Frame:Cycle 8 completion (participants receiving mosunetuzumab), or 5-7 weeks after Cycle 6 (polatuzumab+bendamustine+rituximab participants) (Cycle = 21 days)
Safety Issue:
Description:
Measure:Objective Response Rate (ORR), Defined as CR or PR, Based on PET-CT as Assessed Using Standard Criteria for NHL
Time Frame:Cycle 8 completion (participants receiving mosunetuzumab), or 5-7 weeks after Cycle 6 (polatuzumab+bendamustine+rituximab participants) (Cycle = 21 days)
Safety Issue:
Description:
Measure:Best ORR (CR or PR at any Time) Based on PET-CT or CT Only, as Assessed Using Standard Criteria for NHL
Time Frame:Baseline up to approximately 60 months (assessed at screening and then every 3 months for the first year, then every 6 months until disease progression, start of new anti-cancer therapy, or withdrawal)
Safety Issue:
Description:
Measure:Duration of Response (DOR) as Assessed Using Standard Criteria for NHL
Time Frame:From the first occurrence of a documented response to disease progression, relapse, or death from any cause, whichever occurs first (up to approximately 60 months)
Safety Issue:
Description:
Measure:Progression-Free Survival (PFS) as Assessed Using Standard Criteria for NHL
Time Frame:From randomization to the first occurrence of disease progression, relapse, or death from any cause, whichever occurs first (up to approximately 60 months)
Safety Issue:
Description:
Measure:Event-Free Survival (EFS) as Assessed Using Standard Criteria for NHL
Time Frame:From randomization to the first occurrence of disease progression, relapse, initiation of new anti-lymphoma treatment (NALT), or death from any cause, whichever occurs first (up to approximately 60 months)
Safety Issue:
Description:
Measure:Overall Survival (OS)
Time Frame:From randomization to death from any cause (up to approximately 60 months)
Safety Issue:
Description:
Measure:Time to Deterioration in Health Related Quality of Life
Time Frame:Baseline until disease progression, start of new anti-cancer therapy, or withdrawal (up to approximately 60 months)
Safety Issue:
Description:
Measure:Anti-Drug Antibodies (ADAs) to Mosunetuzumab
Time Frame:At pre-defined intervals from C1D1 through approximately 90 days after the last study treatment
Safety Issue:
Description:
Measure:ADAs to Polatuzumab Vedotin
Time Frame:At pre-defined intervals from C1D1 through approximately 90 days after the last study treatment
Safety Issue:
Description:
Measure:Mosunetuzumab Serum Concentration
Time Frame:At pre-defined intervals from C1D1 through approximately 90 days after the last study treatment
Safety Issue:
Description:

Details

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

Last Updated

February 21, 2020