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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

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ClinicalTrials.gov Identifier: NCT03671018
Recruitment Status : Recruiting
First Posted : September 14, 2018
Last Update Posted : October 4, 2022
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

Tracking Information
First Submitted Date  ICMJE September 10, 2018
First Posted Date  ICMJE September 14, 2018
Last Update Posted Date October 4, 2022
Actual Study Start Date  ICMJE September 25, 2018
Estimated Primary Completion Date June 21, 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 17, 2021)
  • Maximum Tolerated Dose (MTD) of Mosunetuzumab in Combination with Polatuzumab Vedotin [ Time Frame: Cycle 1 to Cycle 2 (cycle length = 21 days) ]
  • Recommended Phase II Dose of Mosunetuzumab in Combination with Polatuzumab Vedotin [ Time Frame: Cycle 1 to Cycle 2 (cycle length = 21 days) ]
  • Percentage of Participants with Adverse Events (AE) [ Time Frame: Baseline through approximately 90 days after last study treatment ]
  • Best Objective Response Rate (ORR), Defined as CR or Partial Response (PR) at any Time, Based on PET-CT and/or CT Scan, as Determined by the Independent Review Committee (IRC) 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) ]
Original Primary Outcome Measures  ICMJE
 (submitted: September 12, 2018)
  • 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: Approximately 6 months after Cycle 1, Day 1 (C1D1) ]
  • Maximum Tolerated Dose (MTD) of Mosunetuzumab in Combination with Polatuzumab Vedotin [ Time Frame: Cycle 1 to Cycle 2 (cycle length = 21 days) ]
  • Recommended Phase II Dose of Mosunetuzumab in Combination with Ploatuzumab Vedotin [ Time Frame: Cycle 1 to Cycle 2 (cycle length = 21 days) ]
  • Percentage of Participants with Adverse Events (AE) [ Time Frame: Baseline through approximately 90 days after last study treatment ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: March 17, 2021)
  • Best ORR (CR or PR at any Time) Based on PET-CT and/or CT Scan, as Determined by the Investigator 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) ]
  • Best CR Rate on Study Based on PET-CT, and/or CT Scan, as Determined by the Investigator and IRC 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) ]
  • CR Rate at the Time of Primary Response Assessment (PRA) Based on PET-CT, as Determined by the Investigator and IRC 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) ]
  • ORR, Defined as CR or PR, at PRA Based on PET-CT as Determined by the Investigator and IRC 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) ]
  • Duration of Response (DOR) as Determined by the Investigator and IRC 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) ]
  • Progression-Free Survival (PFS) as Determined by the Investigator and IRC Using Standard Criteria for NHL [ Time Frame: From time of first study treatment to the first occurrence of disease progression, relapse, or death from any cause, whichever occurs first (up to approximately 60 months) ]
  • Event-Free Survival (EFS) as Determined by the Investigator and IRC Using Standard Criteria for NHL [ Time Frame: From time of first study treatment 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) ]
  • Overall Survival (OS) [ Time Frame: From time of first study treatment to death from any cause (up to approximately 60 months) ]
  • Anti-Drug Antibodies (ADAs) to Mosunetuzumab [ Time Frame: At pre-defined intervals from C1D1 through approximately 90 days after the last study treatment ]
  • ADAs to Polatuzumab Vedotin [ Time Frame: At pre-defined intervals from C1D1 through approximately 90 days after the last study treatment ]
  • Mosunetuzumab Serum Concentration [ Time Frame: At pre-defined intervals from C1D1 through approximately 90 days after the last study treatment ]
Original Secondary Outcome Measures  ICMJE
 (submitted: September 12, 2018)
  • CR Rate Based on PET-CT, as Assessed Using Standard Criteria for NHL [ Time Frame: Approximately 6 months after C1D1 ]
  • CR Rate Based on 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) ]
  • Objective Response Rate (ORR), Defined as CR or PR, Based on PET-CT as Assessed Using Standard Criteria for NHL [ Time Frame: Approximately 6 months after C1D1 ]
  • 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) ]
  • 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) ]
  • 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) ]
  • 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) ]
  • Overall Survival (OS) [ Time Frame: From randomization to death from any cause (up to approximately 60 months) ]
  • 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) ]
  • Anti-Drug Antibodies (ADAs) to Mosunetuzumab [ Time Frame: At pre-defined intervals from C1D1 through approximately 90 days after the last study treatment ]
  • ADAs to Polatuzumab Vedotin [ Time Frame: At pre-defined intervals from C1D1 through approximately 90 days after the last study treatment ]
  • Mosunetuzumab Serum Concentration [ Time Frame: At pre-defined intervals from C1D1 through approximately 90 days after the last study treatment ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study to Evaluate the Safety and Efficacy of Mosunetuzumab (BTCT4465A) in Combination With Polatuzumab Vedotin in B-Cell Non-Hodgkin Lymphoma
Official Title  ICMJE 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
Brief Summary This study will evaluate the safety, tolerability, pharmacokinetics, and efficacy of intravenous 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. In addition, subcutaneous mosunetuzumab in combination with polatuzumab vedotin will be evaluated in participants with at least 2 prior lines of systemic therapy for the treatment of R/R mantle cell lymphoma (MCL).
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE B-cell Non-Hodgkin Lymphoma
Intervention  ICMJE
  • Drug: Mosunetuzumab (IV)
    Participants will receive intravenous (IV) mosunetuzumab.
    Other Name: BTCT4465A
  • Drug: Mosunetuzumab (SC)
    Participants will receive subcutaneous (SC) mosunetuzumab.
  • Drug: Polatuzumab vedotin
    Participants will receive IV polatuzumab vedotin.
  • Drug: Tocilizumab
    Participants will receive IV tocilizumab as needed.
Study Arms  ICMJE
  • 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.
    Interventions:
    • Drug: Mosunetuzumab (IV)
    • Drug: Polatuzumab vedotin
    • Drug: Tocilizumab
  • Experimental: Mosunetuzumab + Polatuzumab Vedotin 2L+ R/R FL
    Participants with at least one line of prior therapy (2L+) and that have relapsed or refractory (R/R) follicular lymphoma (FL) will receive mosunetuzumab + polatuzumab vedotin.
    Interventions:
    • Drug: Mosunetuzumab (IV)
    • Drug: Polatuzumab vedotin
    • Drug: Tocilizumab
  • Experimental: Mosunetuzumab + Polatuzumab Vedotin 2L+R/R DLBCL
    2L+ participants with R/R diffuse large B-cell lymphoma will receive mosunetuzumab + polatuzumab vedotin.
    Interventions:
    • Drug: Mosunetuzumab (IV)
    • Drug: Polatuzumab vedotin
    • Drug: Tocilizumab
  • Experimental: Mosunetuzumab SC + Polatuzumab Vedotin 3L+R/R MCL
    Participants with at least 2 lines of prior therapy (3L+) will receive subcutaneous (SC) mosunetuzumab + polatuzumab vedotin.
    Interventions:
    • Drug: Mosunetuzumab (SC)
    • Drug: Polatuzumab vedotin
    • Drug: Tocilizumab
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: October 29, 2019)
262
Original Estimated Enrollment  ICMJE
 (submitted: September 12, 2018)
276
Estimated Study Completion Date  ICMJE November 18, 2023
Estimated Primary Completion Date June 21, 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Key Inclusion Criteria:

  • ECOG PS of 0, 1, or 2
  • Histologically confirmed FL, DLBCL, or MCL
  • Must have received at least one prior systemic treatment regimen containing an anti-CD20-directed therapy for DLBCL or FL
  • For MCL, participants must have received at least two prior systemic treatment regiments, which include 1) anti-CD20-directed therapy, 2) BTK inhibitor, and 3) anthracycline or bendamustine
  • 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
  • Known or suspected history of hemophagocytic lymphohistiocytosis (HLH)
  • 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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Reference Study ID Number: GO40516 https://forpatients.roche.com/ 888-662-6728 (U.S. and Canada) global.rochegenentechtrials@roche.com
Listed Location Countries  ICMJE Belgium,   Canada,   Spain,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03671018
Other Study ID Numbers  ICMJE GO40516
2018-001141-13 ( EudraCT Number )
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Current Responsible Party Hoffmann-La Roche
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Hoffmann-La Roche
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Clinical Trials Hoffmann-La Roche
PRS Account Hoffmann-La Roche
Verification Date October 2022

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP