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NCT Number: NCT03671018

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

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.

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This study is active but is not currently recruiting participants.

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Key information

Conditions

B-Cell Non-Hodgkin Lymphoma Hemic and Lymphatic Diseases Immune System Diseases Immunoproliferative Disorders Lymphatic Diseases Lymphoma Lymphoma, B-Cell Lymphoma, Non-Hodgkin Lymphoproliferative Disorders Neoplasms Neoplasms by Histologic Type

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1 / Phase 2

Primary location

UZ Brussel, Brussels, Belgium

Loading trial locations.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Mosunetuzumab (IV)

Drug

Participants will receive intravenous (IV) mosunetuzumab.

Other names: BTCT4465A

Mosunetuzumab (SC)

Drug

Participants will receive subcutaneous (SC) mosunetuzumab.

Polatuzumab Vedotin

Drug

Participants will receive IV polatuzumab vedotin.

Tocilizumab

Drug

Participants will receive IV tocilizumab as needed.

Rituximab

Drug

Participants will receive IV rituximab.

Primary outcomes

  1. Maximum Tolerated Dose (MTD) of Mosunetuzumab in Combination with Polatuzumab Vedotin

    Time frame: Cycle 1 to Cycle 2 (cycle length = 21 days)

  2. Recommended Phase II Dose of Mosunetuzumab in Combination with Polatuzumab Vedotin

    Time frame: Cycle 1 to Cycle 2 (cycle length = 21 days)

  3. Percentage of Participants with Adverse Events (AE)

    Time frame: Baseline through approximately 90 days after last study treatment

  4. 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)

Secondary outcomes

  1. 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)

  2. 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)

  3. 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)

  4. 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)

  5. 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)

  6. 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)

  7. 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)

  8. Overall Survival (OS)

    Time frame: From time of first study treatment to death from any cause (up to approximately 60 months)

  9. Anti-Drug Antibodies (ADAs) to Mosunetuzumab

    Time frame: At pre-defined intervals from C1D1 through approximately 90 days after the last study treatment

  10. ADAs to Polatuzumab Vedotin

    Time frame: At pre-defined intervals from C1D1 through approximately 90 days after the last study treatment

  11. Mosunetuzumab Serum Concentration

    Time frame: At pre-defined intervals from C1D1 through approximately 90 days after the last study treatment

Sponsors and collaborators

Lead sponsor

Hoffmann-La Roche

Industry

Registry information

Official study 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

Important dates

Study start
2018
Primary completion
2024
Study completion
2025
First posted
Sep 14, 2018
Registry last updated
Nov 29, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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