Back to resultsA Study to Evaluate the Safety and Efficacy of Mosunetuzumab (BTCT4465A) in Combination With Polatuzumab Vedotin in B-Cell Non-Hodgkin Lymphoma
Primary Purpose
B-cell Non-Hodgkin Lymphoma
Status
Recruiting
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
Mosunetuzumab (IV)
Mosunetuzumab (SC)
Polatuzumab vedotin
Tocilizumab
Rituximab
Sponsored by
About this trial
This is an interventional treatment trial for B-cell Non-Hodgkin Lymphoma
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
Sites / Locations
- University of Alabama at Birmingham School of MedicineRecruiting
- City of HopeRecruiting
- University of Colorado Hospital - Anschutz Cancer PavilionRecruiting
- University of Miami Miller School of MedicineRecruiting
- Moffitt Cancer CenterRecruiting
- University of Michigan Hospital
- Karmanos Cancer InstituteRecruiting
- New York University Langone Medical CenterRecruiting
- Levine Cancer InstituteRecruiting
- Penn State Milton S. Hershey Medical CenterRecruiting
- Fox Chase Cancer Center
- University of Pittsburgh - Hillman Cancer CenterRecruiting
- Lifespan Cancer InstituteRecruiting
- University of Texas M.D. Anderson Cancer CenterRecruiting
- Fred Hutchinson Cancer Research CenterRecruiting
- Medical College of Wisconsin, Froedtert Hospital;Nephrology Section
- UZ Brussel
- CH Jolimont - Lobbes (Jolimont)
- Clinique St Pierre asbl
- Hamilton Health Sciences - Juravinski Cancer Centre
- Jewish General HospitalRecruiting
- Saskatchewan Cancer Agency (SCA) - Saskatoon Cancer Centre (SCC)
- Institut Catala d Oncologia Hospital Duran i ReynalsRecruiting
- Hospital de San Pedro de AlcantaraRecruiting
- Hospital General Universitario Gregorio MarañonRecruiting
- Hospital Infanta Leonor; Servicio de HematologiaRecruiting
- Hospital Universitario Virgen Macarena; Servicio de OncologiaRecruiting
- Cambridge University Hospitals NHS Foundation TrustRecruiting
- Plymouth Hospitals NHS Trust; Pharmacy DeptRecruiting
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm Type
Experimental
Experimental
Experimental
Experimental
Experimental
Arm Label
Dose Finding
Mosunetuzumab + Polatuzumab Vedotin 2L+ R/R FL
Mosunetuzumab + Polatuzumab Vedotin 2L+R/R DLBCL
Mosunetuzumab SC + Polatuzumab Vedotin 3L+R/R MCL
Mosunetuzumab SC + Polatuzumab Vedotin 2L+R/R DLBCL
Arm Description
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.
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.
2L+ participants with R/R diffuse large B-cell lymphoma will receive mosunetuzumab + polatuzumab vedotin.
Participants with at least 2 lines of prior therapy (3L+) will receive subcutaneous (SC) mosunetuzumab + polatuzumab vedotin.
2L+ participants with R/R DLBCL will receive SC mosunetuzumab and polatuzumab vedotin.
Outcomes
Primary Outcome Measures
Maximum Tolerated Dose (MTD) of Mosunetuzumab in Combination with Polatuzumab Vedotin
Recommended Phase II Dose of Mosunetuzumab in Combination with Polatuzumab Vedotin
Percentage of Participants with Adverse Events (AE)
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
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
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
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
ORR, Defined as CR or PR, at PRA Based on PET-CT as Determined by the Investigator and IRC Using Standard Criteria for NHL
Duration of Response (DOR) as Determined by the Investigator and IRC Using Standard Criteria for NHL
Progression-Free Survival (PFS) as Determined by the Investigator and IRC Using Standard Criteria for NHL
Event-Free Survival (EFS) as Determined by the Investigator and IRC Using Standard Criteria for NHL
Overall Survival (OS)
Anti-Drug Antibodies (ADAs) to Mosunetuzumab
ADAs to Polatuzumab Vedotin
Mosunetuzumab Serum Concentration
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03671018
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
Study Type
Interventional
2. Study Status
Record Verification Date
October 2023
Overall Recruitment Status
Recruiting
Study Start Date
September 25, 2018 (Actual)
Primary Completion Date
October 31, 2024 (Anticipated)
Study Completion Date
July 20, 2025 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Hoffmann-La Roche
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
5. Study Description
Brief Summary
This study will evaluate the safety, tolerability, pharmacokinetics, 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
B-cell Non-Hodgkin Lymphoma
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
422 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Dose Finding
Arm Type
Experimental
Arm Description
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.
Arm Title
Mosunetuzumab + Polatuzumab Vedotin 2L+ R/R FL
Arm Type
Experimental
Arm Description
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.
Arm Title
Mosunetuzumab + Polatuzumab Vedotin 2L+R/R DLBCL
Arm Type
Experimental
Arm Description
2L+ participants with R/R diffuse large B-cell lymphoma will receive mosunetuzumab + polatuzumab vedotin.
Arm Title
Mosunetuzumab SC + Polatuzumab Vedotin 3L+R/R MCL
Arm Type
Experimental
Arm Description
Participants with at least 2 lines of prior therapy (3L+) will receive subcutaneous (SC) mosunetuzumab + polatuzumab vedotin.
Arm Title
Mosunetuzumab SC + Polatuzumab Vedotin 2L+R/R DLBCL
Arm Type
Experimental
Arm Description
2L+ participants with R/R DLBCL will receive SC mosunetuzumab and polatuzumab vedotin.
Intervention Type
Drug
Intervention Name(s)
Mosunetuzumab (IV)
Other Intervention Name(s)
BTCT4465A
Intervention Description
Participants will receive intravenous (IV) mosunetuzumab.
Intervention Type
Drug
Intervention Name(s)
Mosunetuzumab (SC)
Intervention Description
Participants will receive subcutaneous (SC) mosunetuzumab.
Intervention Type
Drug
Intervention Name(s)
Polatuzumab vedotin
Intervention Description
Participants will receive IV polatuzumab vedotin.
Intervention Type
Drug
Intervention Name(s)
Tocilizumab
Intervention Description
Participants will receive IV tocilizumab as needed.
Intervention Type
Drug
Intervention Name(s)
Rituximab
Intervention Description
Participants will receive IV rituximab.
Primary Outcome Measure Information:
Title
Maximum Tolerated Dose (MTD) of Mosunetuzumab in Combination with Polatuzumab Vedotin
Time Frame
Cycle 1 to Cycle 2 (cycle length = 21 days)
Title
Recommended Phase II Dose of Mosunetuzumab in Combination with Polatuzumab Vedotin
Time Frame
Cycle 1 to Cycle 2 (cycle length = 21 days)
Title
Percentage of Participants with Adverse Events (AE)
Time Frame
Baseline through approximately 90 days after last study treatment
Title
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 Measure Information:
Title
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)
Title
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)
Title
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)
Title
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)
Title
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)
Title
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)
Title
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)
Title
Overall Survival (OS)
Time Frame
From time of first study treatment to death from any cause (up to approximately 60 months)
Title
Anti-Drug Antibodies (ADAs) to Mosunetuzumab
Time Frame
At pre-defined intervals from C1D1 through approximately 90 days after the last study treatment
Title
ADAs to Polatuzumab Vedotin
Time Frame
At pre-defined intervals from C1D1 through approximately 90 days after the last study treatment
Title
Mosunetuzumab Serum Concentration
Time Frame
At pre-defined intervals from C1D1 through approximately 90 days after the last study treatment
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Reference Study ID Number: GO40516 https://forpatients.roche.com/
Phone
888-662-6728 (U.S. and Canada)
Email
global.rochegenentechtrials@roche.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Trials
Organizational Affiliation
Hoffmann-La Roche
Official's Role
Study Director
Facility Information:
Facility Name
University of Alabama at Birmingham School of Medicine
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35249
Country
United States
Individual Site Status
Recruiting
Facility Name
City of Hope
City
Duarte
State/Province
California
ZIP/Postal Code
91010
Country
United States
Individual Site Status
Recruiting
Facility Name
University of Colorado Hospital - Anschutz Cancer Pavilion
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Individual Site Status
Recruiting
Facility Name
University of Miami Miller School of Medicine
City
Miami
State/Province
Florida
ZIP/Postal Code
33136
Country
United States
Individual Site Status
Recruiting
Facility Name
Moffitt Cancer Center
City
Tampa
State/Province
Florida
ZIP/Postal Code
33612
Country
United States
Individual Site Status
Recruiting
Facility Name
University of Michigan Hospital
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48109
Country
United States
Individual Site Status
Completed
Facility Name
Karmanos Cancer Institute
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48201
Country
United States
Individual Site Status
Recruiting
Facility Name
New York University Langone Medical Center
City
New York
State/Province
New York
ZIP/Postal Code
10016
Country
United States
Individual Site Status
Recruiting
Facility Name
Levine Cancer Institute
City
Charlotte
State/Province
North Carolina
ZIP/Postal Code
28204
Country
United States
Individual Site Status
Recruiting
Facility Name
Penn State Milton S. Hershey Medical Center
City
Hershey
State/Province
Pennsylvania
ZIP/Postal Code
17033
Country
United States
Individual Site Status
Recruiting
Facility Name
Fox Chase Cancer Center
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19111
Country
United States
Individual Site Status
Active, not recruiting
Facility Name
University of Pittsburgh - Hillman Cancer Center
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15232-1301
Country
United States
Individual Site Status
Recruiting
Facility Name
Lifespan Cancer Institute
City
Providence
State/Province
Rhode Island
ZIP/Postal Code
02905
Country
United States
Individual Site Status
Recruiting
Facility Name
University of Texas M.D. Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Individual Site Status
Recruiting
Facility Name
Fred Hutchinson Cancer Research Center
City
Seattle
State/Province
Washington
ZIP/Postal Code
98109
Country
United States
Individual Site Status
Recruiting
Facility Name
Medical College of Wisconsin, Froedtert Hospital;Nephrology Section
City
Milwaukee
State/Province
Wisconsin
ZIP/Postal Code
53226
Country
United States
Individual Site Status
Active, not recruiting
Facility Name
UZ Brussel
City
Brussel
ZIP/Postal Code
1090
Country
Belgium
Individual Site Status
Active, not recruiting
Facility Name
CH Jolimont - Lobbes (Jolimont)
City
Haine-Saint-Paul
ZIP/Postal Code
7100
Country
Belgium
Individual Site Status
Active, not recruiting
Facility Name
Clinique St Pierre asbl
City
Ottignies
ZIP/Postal Code
1340
Country
Belgium
Individual Site Status
Active, not recruiting
Facility Name
Hamilton Health Sciences - Juravinski Cancer Centre
City
Hamilton
State/Province
Ontario
ZIP/Postal Code
L8V 5C2
Country
Canada
Individual Site Status
Active, not recruiting
Facility Name
Jewish General Hospital
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H3T 1E2
Country
Canada
Individual Site Status
Recruiting
Facility Name
Saskatchewan Cancer Agency (SCA) - Saskatoon Cancer Centre (SCC)
City
Saskatoon
State/Province
Saskatchewan
ZIP/Postal Code
S7N 4H4
Country
Canada
Individual Site Status
Active, not recruiting
Facility Name
Institut Catala d Oncologia Hospital Duran i Reynals
City
Barcelona
ZIP/Postal Code
08908
Country
Spain
Individual Site Status
Recruiting
Facility Name
Hospital de San Pedro de Alcantara
City
Caceres
ZIP/Postal Code
10003
Country
Spain
Individual Site Status
Recruiting
Facility Name
Hospital General Universitario Gregorio Marañon
City
Madrid
ZIP/Postal Code
28007
Country
Spain
Individual Site Status
Recruiting
Facility Name
Hospital Infanta Leonor; Servicio de Hematologia
City
Madrid
ZIP/Postal Code
28031
Country
Spain
Individual Site Status
Recruiting
Facility Name
Hospital Universitario Virgen Macarena; Servicio de Oncologia
City
Sevilla
ZIP/Postal Code
41009
Country
Spain
Individual Site Status
Recruiting
Facility Name
Cambridge University Hospitals NHS Foundation Trust
City
Cambridge
ZIP/Postal Code
CB2 0QQ
Country
United Kingdom
Individual Site Status
Recruiting
Facility Name
Plymouth Hospitals NHS Trust; Pharmacy Dept
City
Plymouth
ZIP/Postal Code
PL6 8DH
Country
United Kingdom
Individual Site Status
Recruiting
12. IPD Sharing Statement
Learn more about this trial
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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