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

• ClinicalTrials.gov Identifier: NCT03671018
• Recruitment Status: Active, not recruiting
• First Posted: September 14, 2018
• Last Update Posted: March 18, 2024
• Sponsor: Hoffmann-La Roche
• Information provided by (Responsible Party): Hoffmann-La Roche

Tracking Information

• First Submitted Date: September 10, 2018
• First Posted Date: September 14, 2018
• Last Update Posted Date: March 18, 2024
• Actual Study Start Date: September 25, 2018
• Actual Primary Completion Date: January 30, 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (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 (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 ]

Current Secondary Outcome Measures (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 (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: 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
• Brief Summary: This study will evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and efficacy of intravenous (IV) or subcutaneous (SC) mosunetuzumab in combination with polatuzumab vedotin in participants with diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), and mantle cell lymphoma (MCL). 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 (3L+) for the treatment of R/R mantle cell lymphoma (MCL) and in participants with 2L+ R/R DLBCL.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1; Phase 2
• Study Design: Allocation: Non-Randomized; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: B-cell Non-Hodgkin Lymphoma

Intervention

• 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.
• Drug: Rituximab
  Participants will receive IV rituximab.

Study Arms

• 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
  • Drug: Rituximab
• 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
• Experimental: Mosunetuzumab SC + Polatuzumab Vedotin 2L+R/R DLBCL
  2L+ participants with R/R DLBCL will receive SC mosunetuzumab and polatuzumab vedotin.
  Interventions:

  • Drug: Mosunetuzumab (SC)
  • Drug: Polatuzumab vedotin
  • Drug: Tocilizumab

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Estimated Enrollment (submitted: October 13, 2022): 422
• Original Estimated Enrollment (submitted: September 12, 2018): 276
• Estimated Study Completion Date: July 20, 2025
• Actual Primary Completion Date: January 30, 2024 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Belgium, Canada, Spain, United Kingdom, United States

Administrative Information

• NCT Number: NCT03671018
• Other Study ID Numbers: 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: Not Provided
• Current Responsible Party: Hoffmann-La Roche
• Original Responsible Party: Same as current
• Current Study Sponsor: Hoffmann-La Roche
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Clinical Trials; Hoffmann-La Roche

• PRS Account: Hoffmann-La Roche
• Verification Date: March 2024