A Study to Evaluate the Safety and Efficacy of Mosunetuzumab (BTCT4465A) in Combination With Polatuzumab Vedotin in B-Cell Non-Hodgkin Lymphoma
- Conditions
- B-cell Non-Hodgkin Lymphoma
- Interventions
- Registration Number
- NCT03671018
- Lead Sponsor
- Hoffmann-La Roche
- 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 available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 422
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Dose Finding Tocilizumab 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 + Polatuzumab Vedotin 2L+ R/R FL Tocilizumab 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 + Polatuzumab Vedotin 2L+R/R DLBCL Tocilizumab 2L+ participants with R/R diffuse large B-cell lymphoma will receive mosunetuzumab + polatuzumab vedotin. Mosunetuzumab + Polatuzumab Vedotin 2L+R/R DLBCL Rituximab 2L+ participants with R/R diffuse large B-cell lymphoma will receive mosunetuzumab + polatuzumab vedotin. Mosunetuzumab SC + Polatuzumab Vedotin 3L+R/R MCL Polatuzumab vedotin Participants with at least 2 lines of prior therapy (3L+) will receive subcutaneous (SC) mosunetuzumab + polatuzumab vedotin. Mosunetuzumab SC + Polatuzumab Vedotin 2L+R/R DLBCL Polatuzumab vedotin 2L+ participants with R/R DLBCL will receive SC mosunetuzumab and polatuzumab vedotin. Dose Finding Mosunetuzumab (IV) 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. Dose Finding Polatuzumab vedotin 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 + Polatuzumab Vedotin 2L+R/R DLBCL Mosunetuzumab (IV) 2L+ participants with R/R diffuse large B-cell lymphoma will receive mosunetuzumab + polatuzumab vedotin. Mosunetuzumab SC + Polatuzumab Vedotin 2L+R/R DLBCL Mosunetuzumab (SC) 2L+ participants with R/R DLBCL will receive SC mosunetuzumab and polatuzumab vedotin. Mosunetuzumab SC + Polatuzumab Vedotin 2L+R/R DLBCL Tocilizumab 2L+ participants with R/R DLBCL will receive SC mosunetuzumab and polatuzumab vedotin. Mosunetuzumab + Polatuzumab Vedotin 2L+ R/R FL Polatuzumab vedotin 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 SC + Polatuzumab Vedotin 3L+R/R MCL Mosunetuzumab (SC) Participants with at least 2 lines of prior therapy (3L+) will receive subcutaneous (SC) mosunetuzumab + polatuzumab vedotin. Mosunetuzumab + Polatuzumab Vedotin 2L+ R/R FL Mosunetuzumab (IV) 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 + Polatuzumab Vedotin 2L+R/R DLBCL Polatuzumab vedotin 2L+ participants with R/R diffuse large B-cell lymphoma will receive mosunetuzumab + polatuzumab vedotin. Mosunetuzumab SC + Polatuzumab Vedotin 3L+R/R MCL Tocilizumab Participants with at least 2 lines of prior therapy (3L+) will receive subcutaneous (SC) mosunetuzumab + polatuzumab vedotin.
- Primary Outcome Measures
Name Time Method Maximum Tolerated Dose (MTD) of Mosunetuzumab in Combination with Polatuzumab Vedotin Cycle 1 to Cycle 2 (cycle length = 21 days) Recommended Phase II Dose of Mosunetuzumab in Combination with Polatuzumab Vedotin Cycle 1 to Cycle 2 (cycle length = 21 days) Percentage of Participants with Adverse Events (AE) 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 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
Name Time Method ADAs to Polatuzumab Vedotin At pre-defined intervals from C1D1 through approximately 90 days after the last study treatment Mosunetuzumab Serum Concentration At pre-defined intervals from C1D1 through approximately 90 days after the last study treatment 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 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 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 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 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 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 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) From time of first study treatment to death from any cause (up to approximately 60 months) Anti-Drug Antibodies (ADAs) to Mosunetuzumab At pre-defined intervals from C1D1 through approximately 90 days after the last study treatment ORR, Defined as CR or PR, at PRA Based on PET-CT as Determined by the Investigator and IRC Using Standard Criteria for NHL Cycle 8 completion (participants receiving mosunetuzumab), or 5-7 weeks after Cycle 6 (polatuzumab+bendamustine+rituximab participants) (Cycle = 21 days)
Trial Locations
- Locations (29)
University of Pittsburgh - Hillman Cancer Center
🇺🇸Pittsburgh, Pennsylvania, United States
University of Miami Miller School of Medicine
🇺🇸Miami, Florida, United States
University of Texas M.D. Anderson Cancer Center
🇺🇸Houston, Texas, United States
Fred Hutchinson Cancer Research Center
🇺🇸Seattle, Washington, United States
City of Hope
🇺🇸Duarte, California, United States
Karmanos Cancer Institute
🇺🇸Detroit, Michigan, United States
Clinique St Pierre asbl
🇧🇪Ottignies, Belgium
Hospital Universitario Virgen Macarena; Servicio de Oncologia
🇪🇸Sevilla, Spain
Cambridge University Hospitals NHS Foundation Trust
🇬🇧Cambridge, United Kingdom
Medical College of Wisconsin, Froedtert Hospital;Nephrology Section
🇺🇸Milwaukee, Wisconsin, United States
University of Alabama at Birmingham School of Medicine
🇺🇸Birmingham, Alabama, United States
Hospital de San Pedro de Alcantara
🇪🇸Caceres, Spain
University of Colorado Hospital - Anschutz Cancer Pavilion
🇺🇸Aurora, Colorado, United States
University of Michigan Hospital
🇺🇸Ann Arbor, Michigan, United States
Moffitt Cancer Center
🇺🇸Tampa, Florida, United States
New York University Langone Medical Center
🇺🇸New York, New York, United States
Levine Cancer Institute
🇺🇸Charlotte, North Carolina, United States
Penn State Milton S. Hershey Medical Center
🇺🇸Hershey, Pennsylvania, United States
Fox Chase Cancer Center
🇺🇸Philadelphia, Pennsylvania, United States
Lifespan Cancer Institute
🇺🇸Providence, Rhode Island, United States
UZ Brussel
🇧🇪Brussel, Belgium
CH Jolimont - Lobbes (Jolimont)
🇧🇪Haine-Saint-Paul, Belgium
Jewish General Hospital
🇨🇦Montreal, Quebec, Canada
Hamilton Health Sciences - Juravinski Cancer Centre
🇨🇦Hamilton, Ontario, Canada
Hospital Infanta Leonor; Servicio de Hematologia
🇪🇸Madrid, Spain
Hospital General Universitario Gregorio Marañon
🇪🇸Madrid, Spain
Institut Catala d Oncologia Hospital Duran i Reynals
🇪🇸Barcelona, Spain
Plymouth Hospitals NHS Trust; Pharmacy Dept
🇬🇧Plymouth, United Kingdom
Saskatchewan Cancer Agency (SCA) - Saskatoon Cancer Centre (SCC)
🇨🇦Saskatoon, Saskatchewan, Canada