Clinical trial NCT03671018: 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
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
PHASE2
Conditions: B-cell Non-Hodgkin Lymphoma
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2018-09-14
Enrollment: 422
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Maximum Tolerated Dose (MTD) of Mosunetuzumab in Combination with Polatuzumab Vedotin
timeFrame: Cycle 1 to Cycle 2 (cycle length = 21 days)
measure: Recommended Phase II Dose of Mosunetuzumab in Combination with Polatuzumab Vedotin
timeFrame: Cycle 1 to Cycle 2 (cycle length = 21 days)
measure: Percentage of Participants with Adverse Events (AE)
timeFrame: Baseline through approximately 90 days after last study treatment
measure: 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
timeFrame: 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 outcomes:
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
timeFrame: 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)
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
timeFrame: 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)
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
timeFrame: Cycle 8 completion (participants receiving mosunetuzumab), or 5-7 weeks after Cycle 6 (polatuzumab+bendamustine+rituximab participants) (Cycle = 21 days)
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
timeFrame: Cycle 8 completion (participants receiving mosunetuzumab), or 5-7 weeks after Cycle 6 (polatuzumab+bendamustine+rituximab participants) (Cycle = 21 days)
measure: Duration of Response (DOR) as Determined by the Investigator and IRC Using Standard Criteria for NHL
timeFrame: 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)
measure: Progression-Free Survival (PFS) as Determined by the Investigator and IRC Using Standard Criteria for NHL
timeFrame: 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)
measure: Event-Free Survival (EFS) as Determined by the Investigator and IRC Using Standard Criteria for NHL
timeFrame: 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)
measure: Overall Survival (OS)
timeFrame: From time of first study treatment to death from any cause (up to approximately 60 months)
measure: Anti-Drug Antibodies (ADAs) to Mosunetuzumab
timeFrame: At pre-defined intervals from C1D1 through approximately 90 days after the last study treatment
measure: ADAs to Polatuzumab Vedotin
timeFrame: At pre-defined intervals from C1D1 through approximately 90 days after the last study treatment
measure: Mosunetuzumab Serum Concentration
timeFrame: At pre-defined intervals from C1D1 through approximately 90 days after the last study treatment
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham School of Medicine
state: Alabama
city: Duarte
country: United States
facility: City of Hope
state: California
city: Aurora
country: United States
facility: University of Colorado Hospital - Anschutz Cancer Pavilion
state: Colorado
city: Miami
country: United States
facility: University of Miami Miller School of Medicine
state: Florida
city: Tampa
country: United States
facility: Moffitt Cancer Center
state: Florida
city: Ann Arbor
country: United States
facility: University of Michigan Hospital
state: Michigan
city: Detroit
country: United States
facility: Karmanos Cancer Institute
state: Michigan
city: New York
country: United States
facility: New York University Langone Medical Center
state: New York
city: Charlotte
country: United States
facility: Levine Cancer Institute
state: North Carolina
city: Hershey
country: United States
facility: Penn State Milton S. Hershey Medical Center
state: Pennsylvania
city: Philadelphia
country: United States
facility: Fox Chase Cancer Center
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh - Hillman Cancer Center
state: Pennsylvania
city: Providence
country: United States
facility: Lifespan Cancer Institute
state: Rhode Island
city: Houston
country: United States
facility: University of Texas M.D. Anderson Cancer Center
state: Texas
city: Seattle
country: United States
facility: Fred Hutchinson Cancer Research Center
state: Washington
city: Milwaukee
country: United States
facility: Medical College of Wisconsin, Froedtert Hospital;Nephrology Section
state: Wisconsin
city: Brussel
country: Belgium
facility: UZ Brussel
city: Haine-Saint-Paul
country: Belgium
facility: CH Jolimont - Lobbes (Jolimont)
city: Ottignies
country: Belgium
facility: Clinique St Pierre asbl
city: Hamilton
country: Canada
facility: Hamilton Health Sciences - Juravinski Cancer Centre
state: Ontario
city: Montreal
country: Canada
facility: Jewish General Hospital
state: Quebec
city: Saskatoon
country: Canada
facility: Saskatchewan Cancer Agency (SCA) - Saskatoon Cancer Centre (SCC)
state: Saskatchewan
city: Barcelona
country: Spain
facility: Institut Catala d Oncologia Hospital Duran i Reynals
city: Caceres
country: Spain
facility: Hospital de San Pedro de Alcantara
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Marañon
city: Madrid
country: Spain
facility: Hospital Infanta Leonor; Servicio de Hematologia
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen Macarena; Servicio de Oncologia
city: Cambridge
country: United Kingdom
facility: Cambridge University Hospitals NHS Foundation Trust
city: Plymouth
country: United Kingdom
facility: Plymouth Hospitals NHS Trust; Pharmacy Dept
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: