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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 : December 11, 2018
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

Brief Summary:
This study will evaluate the safety, tolerability, pharmacokinetics, and efficacy of mosunetuzumab in combination with polatuzumab vedotin in participants with B-cell non-Hodgkin lymphoma (NHL). It will consist of a dose finding portion and two randomized cohorts for participants with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) or follicular lymphoma (FL).

Condition or disease Intervention/treatment Phase
B-cell Non-Hodgkin Lymphoma Drug: Mosunetuzumab Drug: Polatuzumab vedotin Drug: Rituximab Drug: Bendamustine Drug: Obinutuzumab Drug: Cyclophosphamide Drug: Doxorubicin Drug: Vincristine Drug: Prednisone Drug: Tocilizumab Phase 1

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 276 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : September 25, 2018
Estimated Primary Completion Date : April 30, 2023
Estimated Study Completion Date : September 28, 2023

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lymphoma

Arm Intervention/treatment
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.
Drug: Mosunetuzumab
Participants will receive intravenous (IV) mosunetuzumab.
Other Name: BTCT4465A

Drug: Polatuzumab vedotin
Participants will receive IV polatuzumab vedotin.

Drug: Tocilizumab
Participants will receive IV tocilizumab as needed.

Active Comparator: Bendamustine + Rituximab + Polatuzumab Vedotin
Participants with DLBCL randomized to this arm will receive bendamustine + rituxumab + polatuzumab vedotin.
Drug: Polatuzumab vedotin
Participants will receive IV polatuzumab vedotin.

Drug: Rituximab
Participants will receive IV rituxumab.

Drug: Bendamustine
Participants will receive IV bendamustine.

Active Comparator: Rituxumab-Chemotherapy/Bendamustine + Obinutuzumab
Participants with FL randomized to this arm will receive investigator's choice of either rituximab + cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP), rituximab + cyclophosphamide, vincristine, and prednisone (R-CVP), or obinutuzumab + bendamustine followed by obinutuzumab maintenance.
Drug: Rituximab
Participants will receive IV rituxumab.

Drug: Bendamustine
Participants will receive IV bendamustine.

Drug: Obinutuzumab
Participants will receive IV obinutuzumab.

Drug: Cyclophosphamide
Participants will receive IV cyclophosphamide.

Drug: Doxorubicin
Participants will receive IV doxorubicin.

Drug: Vincristine
Participants will receive IV vincristine.

Drug: Prednisone
Participants will receive oral prednisone.

Experimental: Mosunetuzumab FL
Participants with FL randomized to this arm will receive mosunetuzumab at the recommended Phase II dose (RP2D) as a single-agent.
Drug: Mosunetuzumab
Participants will receive intravenous (IV) mosunetuzumab.
Other Name: BTCT4465A

Drug: Tocilizumab
Participants will receive IV tocilizumab as needed.

Experimental: Mosunetuzumab DLBCL
Participants with DLBCL randomized to this arm will receive mosunetuzumab at the RP2D as a single agent.
Drug: Mosunetuzumab
Participants will receive intravenous (IV) mosunetuzumab.
Other Name: BTCT4465A

Drug: Tocilizumab
Participants will receive IV tocilizumab as needed.

Experimental: Mosunetuzumab + Polatuzumab Vedotin FL
Participants with FL randomized to this arm will receive mosunetuzumab at the RP2D in combination with polatuzumab vedotin.
Drug: Mosunetuzumab
Participants will receive intravenous (IV) mosunetuzumab.
Other Name: BTCT4465A

Drug: Polatuzumab vedotin
Participants will receive IV polatuzumab vedotin.

Drug: Tocilizumab
Participants will receive IV tocilizumab as needed.

Experimental: Mosunetuzumab + Polatuzumab Vedotin DLBCL
Participants with DLBCL randomized to this arm will receive mosunetuzumab at the RP2D in combination with polatuzumab vedotin.
Drug: Mosunetuzumab
Participants will receive intravenous (IV) mosunetuzumab.
Other Name: BTCT4465A

Drug: Polatuzumab vedotin
Participants will receive IV polatuzumab vedotin.

Drug: Tocilizumab
Participants will receive IV tocilizumab as needed.




Primary Outcome Measures :
  1. 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) ]
  2. Maximum Tolerated Dose (MTD) of Mosunetuzumab in Combination with Polatuzumab Vedotin [ Time Frame: Cycle 1 to Cycle 2 (cycle length = 21 days) ]
  3. Recommended Phase II Dose of Mosunetuzumab in Combination with Ploatuzumab Vedotin [ Time Frame: Cycle 1 to Cycle 2 (cycle length = 21 days) ]
  4. Percentage of Participants with Adverse Events (AE) [ Time Frame: Baseline through approximately 90 days after last study treatment ]

Secondary Outcome Measures :
  1. CR Rate Based on PET-CT, as Assessed Using Standard Criteria for NHL [ Time Frame: Approximately 6 months after C1D1 ]
  2. 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) ]
  3. 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 ]
  4. 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) ]
  5. 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) ]
  6. 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) ]
  7. 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) ]
  8. Overall Survival (OS) [ Time Frame: From randomization to death from any cause (up to approximately 60 months) ]
  9. 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) ]
  10. Anti-Drug Antibodies (ADAs) to Mosunetuzumab [ Time Frame: At pre-defined intervals from C1D1 through approximately 90 days after the last study treatment ]
  11. ADAs to Polatuzumab Vedotin [ Time Frame: At pre-defined intervals from C1D1 through approximately 90 days after the last study treatment ]
  12. Mosunetuzumab Serum Concentration [ Time Frame: At pre-defined intervals from C1D1 through approximately 90 days after the last study treatment ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03671018


Contacts
Contact: Reference Study ID Number: GO40516 www.roche.com/about_roche/roche_worldwide.htm 888-662-6728 (U.S. and Canada) global.rochegenentechtrials@roche.com

Locations
United States, California
City of Hope Recruiting
Duarte, California, United States, 91010
United States, Florida
University of Miami Miller School of Medicine Recruiting
Miami, Florida, United States, 33136
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
Study Director: Clinical Trials Hoffmann-La Roche

Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT03671018     History of Changes
Other Study ID Numbers: GO40516
2018-001141-13 ( EudraCT Number )
First Posted: September 14, 2018    Key Record Dates
Last Update Posted: December 11, 2018
Last Verified: December 2018

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Lymphoma
Lymphoma, Non-Hodgkin
Lymphoma, B-Cell
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Cyclophosphamide
Rituximab
Bendamustine Hydrochloride
Liposomal doxorubicin
Obinutuzumab
Doxorubicin
Prednisone
Vincristine
Antibodies, Monoclonal
Immunoconjugates
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antibiotics, Antineoplastic
Topoisomerase II Inhibitors