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 |
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Recruitment Status :
Active, not recruiting
First Posted : September 14, 2018
Last Update Posted : March 18, 2024
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Sponsor:
Hoffmann-La Roche
Information provided by (Responsible Party):
Hoffmann-La Roche
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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.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| B-cell Non-Hodgkin Lymphoma | Drug: Mosunetuzumab (IV) Drug: Mosunetuzumab (SC) Drug: Polatuzumab vedotin Drug: Tocilizumab Drug: Rituximab | Phase 1 Phase 2 |
| Study Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 422 participants |
| Allocation: | Non-Randomized |
| Intervention Model: | Single Group 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 |
| Actual Primary Completion Date : | January 30, 2024 |
| Estimated Study Completion Date : | July 20, 2025 |
Resource links provided by the National Library of Medicine
MedlinePlus related topics:
Lymphoma
Drug Information
available for:
Polatuzumab vedotin
| Arm | Intervention/treatment |
|---|---|
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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.
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Drug: Mosunetuzumab (IV)
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. |
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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.
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Drug: Mosunetuzumab (IV)
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. |
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Experimental: Mosunetuzumab + Polatuzumab Vedotin 2L+R/R DLBCL
2L+ participants with R/R diffuse large B-cell lymphoma will receive mosunetuzumab + polatuzumab vedotin.
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Drug: Mosunetuzumab (IV)
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. Drug: Rituximab Participants will receive IV rituximab. |
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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.
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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. |
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Experimental: Mosunetuzumab SC + Polatuzumab Vedotin 2L+R/R DLBCL
2L+ participants with R/R DLBCL will receive SC mosunetuzumab and polatuzumab vedotin.
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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. |
Primary Outcome Measures :
- 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) ]
Secondary Outcome Measures :
- 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 ]
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, 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
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
Locations
Show 29 study locations
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
| Study Director: | Clinical Trials | Hoffmann-La Roche |
| Responsible Party: | Hoffmann-La Roche |
| ClinicalTrials.gov Identifier: | NCT03671018 |
| Other Study ID Numbers: |
GO40516 2018-001141-13 ( EudraCT Number ) |
| First Posted: | September 14, 2018 Key Record Dates |
| Last Update Posted: | March 18, 2024 |
| Last Verified: | March 2024 |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
Additional relevant MeSH terms:
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Lymphoma Lymphoma, Non-Hodgkin Lymphoma, B-Cell Neoplasms by Histologic Type Neoplasms Lymphoproliferative Disorders Lymphatic Diseases Immunoproliferative Disorders Immune System Diseases |
Rituximab Polatuzumab vedotin Antineoplastic Agents, Immunological Antineoplastic Agents Immunologic Factors Physiological Effects of Drugs Antirheumatic Agents Immunoconjugates |