Description:
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).
Title
- 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
Clinical Trial IDs
- ORG STUDY ID:
GO40516
- SECONDARY ID:
2018-001141-13
- NCT ID:
NCT03671018
Conditions
- B-cell Non-Hodgkin Lymphoma
Interventions
Drug | Synonyms | Arms |
---|
Mosunetuzumab (IV) | BTCT4465A | Dose Finding |
Mosunetuzumab (SC) | | Mosunetuzumab SC + Polatuzumab Vedotin 3L+R/R MCL |
Polatuzumab vedotin | | Dose Finding |
Tocilizumab | | Dose Finding |
Purpose
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).
Trial Arms
Name | Type | Description | Interventions |
---|
Dose Finding | Experimental | 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. | - Mosunetuzumab (IV)
- Polatuzumab vedotin
- Tocilizumab
|
Mosunetuzumab + Polatuzumab Vedotin 2L+ R/R FL | Experimental | 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. | - Mosunetuzumab (IV)
- Polatuzumab vedotin
- Tocilizumab
|
Mosunetuzumab + Polatuzumab Vedotin 2L+R/R DLBCL | Experimental | 2L+ participants with R/R diffuse large B-cell lymphoma will receive mosunetuzumab + polatuzumab vedotin. | - Mosunetuzumab (IV)
- Polatuzumab vedotin
- Tocilizumab
|
Mosunetuzumab SC + Polatuzumab Vedotin 3L+R/R MCL | Experimental | Participants with at least 2 lines of prior therapy (3L+) will receive subcutaneous (SC) mosunetuzumab + polatuzumab vedotin. | - Mosunetuzumab (SC)
- Polatuzumab vedotin
- Tocilizumab
|
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
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Maximum Tolerated Dose (MTD) of Mosunetuzumab in Combination with Polatuzumab Vedotin |
Time Frame: | Cycle 1 to Cycle 2 (cycle length = 21 days) |
Safety Issue: | |
Description: | |
Secondary Outcome Measures
Measure: | 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) |
Safety Issue: | |
Description: | |
Measure: | 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) |
Safety Issue: | |
Description: | |
Measure: | 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) |
Safety Issue: | |
Description: | |
Measure: | 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) |
Safety Issue: | |
Description: | |
Measure: | 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) |
Safety Issue: | |
Description: | |
Measure: | 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) |
Safety Issue: | |
Description: | |
Measure: | 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) |
Safety Issue: | |
Description: | |
Measure: | Overall Survival (OS) |
Time Frame: | From time of first study treatment to death from any cause (up to approximately 60 months) |
Safety Issue: | |
Description: | |
Measure: | Anti-Drug Antibodies (ADAs) to Mosunetuzumab |
Time Frame: | At pre-defined intervals from C1D1 through approximately 90 days after the last study treatment |
Safety Issue: | |
Description: | |
Measure: | ADAs to Polatuzumab Vedotin |
Time Frame: | At pre-defined intervals from C1D1 through approximately 90 days after the last study treatment |
Safety Issue: | |
Description: | |
Measure: | Mosunetuzumab Serum Concentration |
Time Frame: | At pre-defined intervals from C1D1 through approximately 90 days after the last study treatment |
Safety Issue: | |
Description: | |
Details
Phase: | Phase 1/Phase 2 |
Primary Purpose: | Interventional |
Overall Status: | Recruiting |
Lead Sponsor: | Hoffmann-La Roche |
Last Updated
August 5, 2021