Clinical trial NCT03677141: A Phase Ib/II Study Investigating the Safety, Tolerability, Pharmacokinetics, and Efficacy of Mosunetuzumab (BTCT4465A) in Combination With CHOP or CHP-Polatuzumab Vedotin in Participants With B-Cell Non-Hodgkin Lymphoma
Official title: A Phase Ib/II, Open-Label, Multicenter, Randomized, Controlled Study Investigating the Safety, Tolerability, Pharmacokinetics, and Efficacy of Mosunetuzumab (BTCT4465A) in Combination With CHOP or CHP-Polatuzumab Vedotin in Patients With B-Cell Non-Hodgkin Lymphoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: B-cell Non-Hodgkin Lymphoma
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2018-09-19
Enrollment: 117
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study will evaluate the safety, pharmacokinetics, and preliminary efficacy of mosunetuzumab in combination with cyclophosphamide, doxorubicin, vincristine, and prednisone (M-CHOP) and, subsequently, in combination with cyclophosphamide, doxorubicin, and prednisone (CHP) plus polatuzumab vedotin (CHP-pola) in participants with relapsed or refractory (R/R) B-cell non-Hodgkin lymphoma (NHL), and in previously untreated participants with diffuse large B-cell lymphoma (DLBCL).


Eligibility criteria: Inclusion Criteria for Phase Ib and Phase II Portions

* At least one bi-dimensionally measurable nodal lesion, defined as \> 1.5 cm in its longest dimension, or one bi-dimensionally measurable extranodal lesion, defined as \> 1.0 cm in its longest diameter
* Eastern Cooperative Oncology Group Performance Status of 0, 1, or 2
* Adequate hematologic function

Inclusion Criteria for Phase Ib Portion

Participants must also meet the following criteria for study entry into the Phase Ib portion:

* Histologically confirmed B-cell NHL according to the World Health Organization (WHO) 2016 classification expected to express the cluster of differentiation-20 (CD20) antigen
* Relapsed or refractory (R/R) B-cell NHL after at least one prior systemic lymphoma therapy
* Treatment with at least one prior CD20-directed therapy
* Group B only: no prior treatment with polatuzumab vedotin

Inclusion Criteria for Phase II Portion

Participants must also meet the following criteria for study entry in the Phase II portion:

* Previously untreated, histologically confirmed DLBCL according to WHO 2016 classification
* International Prognostic Index (IPI) score of 2-5

Exclusion Criteria

* Prior treatment with mosunetuzumab
* Prior allogenic stem-cell transplant
* Current Grade \>1 peripheral neuropathy
* Participants with history of confirmed progressive multifocal leukoencephalopathy (PML)
* Known or suspected chronic active Epstein Barr virus (CAEBV), hepatitis B, hepatitis C (HCV), or Human Immunodeficiency Virus (HIV)
* Prior solid organ transplantation
* History of autoimmune disease
* Current or past history of central nervous system (CNS) lymphoma
* Current or past history of CNS disease, such as stroke, epilepsy, CNS vasculitis, or neurodegenerative disease
* Significant cardiovascular disease or pulmonary disease
* Clinically significant history of liver disease
* Recent major surgery within 4 weeks before the start of C1D1, other than superficial lymph node biopsies for diagnosis

Exclusion Criteria for Phase Ib Portion

Participants who also meet any of the following criteria will be excluded from study entry in the Phase Ib portion:

* Prior treatment with chemotherapy, immunotherapy, and biologic therapy 4 weeks prior to C1D1
* Prior treatment with radiotherapy within 2 weeks prior to C1D1
* Adverse events from prior anti-cancer therapy resolved to ≤Grade 1 (with the exception of alopecia and anorexia)
* Prior treatment with \>250 mg/m\^2 doxorubicin (or equivalent anthracycline dose)

Exclusion Criteria for Phase II Portion

Participants who also meet any of the following criteria will be excluded from study entry in the Phase II portion:

* Participants with transformed lymphoma
* Prior therapy for B-cell NHL

Primary outcomes:
measure: Complete Response (CR) Rate at the Time of Primary Response Assessment (PRA) Based on Positron Emission Tomography - Computed Tomography (PET-CT) as Determined by Independent Review Committee (IRC)
timeFrame: 6-8 weeks after either C6D1 or last dose of study treatment
Secondary outcomes:
measure: CR Rate at PRA Based on CT Only as Determined by the Investigator (Phase II)
timeFrame: 6-8 weeks after C6D1 or last dose of study treatment
measure: Overall Response Rate (ORR) at PRA Based on PET-CT as Determined by the Investigator (Phase II)
timeFrame: 6-8 weeks after C6D1 or last dose of study treatment
measure: ORR at PRA Based on CT Only as Determined by the Investigator (Phase II)
timeFrame: 6-8 weeks after C6D1 or last dose of study treatment
measure: Best ORR Based on PET-CT and/or CT Scan as Determined by the Investigator (Phase II)
timeFrame: Up to approximately 50 months
measure: Duration of Response (DOR) as Determined by the Investigator (Phase II)
timeFrame: Up to approximately 50 months
measure: Progression-free Survival (PFS) as Determined by the Investigator (Phase II)
timeFrame: Up to approximately 50 months
measure: PFS at 1 Year as Determined by the Investigator (Phase II)
timeFrame: 1 year
measure: Event-free Survival (EFS) as Determined by the Investigator (Phase II)
timeFrame: Up to 50 months
measure: Time to Deterioration in Lymphoma Symptoms as Measured by the Functional Assessment of Cancer Therapy - Lymphoma (FACT-Lym) Subscale
timeFrame: C1D1 through follow-up period (to begin 2 years after PRA or at the time of study drug discontinuation)
measure: Time to Deterioration in Physical Functioning and Fatigue as Measured by the European Organization for Research and Treatment of Cancer Quality of Life - Core 30 Questionnaire (EORTC QLQ-C30)
timeFrame: C1D1 through follow-up period (to begin 2 years after PRA or at the time of study drug discontinuation)
measure: Polatuzumab Vedotin Serum Concentrations
timeFrame: C2D1, C6D1
measure: Polatuzumab Vedotin Antibody-conjugated Monomethyl Auristatin E (acMMAE) Serum Concentrations
timeFrame: C1D1-C6D1
measure: Polatuzumab Vedotin Unconjugated Mono-methyl Auristatin E (MMAE) Serum Concentrations
timeFrame: C1D1-C6D1
measure: Mosunetuzumab Serum Concentrations
timeFrame: C1D1-C5D1
measure: Baseline Prevalence and Incidence of Treatment Emergent Anti-drug Antibodies (ADA) to Mosunetuzumab
timeFrame: Cycles 1, 2, 6, 16, and at early discontinuation visit or at PRA (6-8 weeks after either C6D1 or last dose of study treatment)
measure: Baseline Prevalence and Incidence of Treatment Emergent ADA to Polatuzumab Vedotin
timeFrame: Cycles 1, 2, 6, and at early discontinuation visit or at PRA (6-8 weeks after either C6D1 or last dose of study treatment)
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama Birmingham
state: Alabama
city: Gilbert
country: United States
facility: Banner MD Anderson Cancer Center
state: Arizona
city: La Jolla
country: United States
facility: University of California; Moores Cancer Center
state: California
city: Santa Monica
country: United States
facility: University of California, Los Angeles (UCLA) - Hematology/Oncology Santa Monica
state: California
city: Washington
country: United States
facility: Georgetown University Medical Center
state: District of Columbia
city: Miami
country: United States
facility: University of Miami Miller School of Medicine
state: Florida
city: Westwood
country: United States
facility: University of Kansas Cancer Center
state: Kansas
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic Cancer Center
state: Minnesota
city: Providence
country: United States
facility: Rhode Island Hospital
state: Rhode Island
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Houston
country: United States
facility: The University of Texas MD Anderson Cancer Center
state: Texas
city: Temple
country: United States
facility: Scott and White Hospital; Cancer Center
state: Texas
city: Milwaukee
country: United States
facility: Medical College of Wisconsin, Inc.
state: Wisconsin
city: Salzburg
country: Austria
facility: Uniklinikum Salzburg, LKH; Univ.Klinik f. Innere Medizin III der PMU
city: Steyr
country: Austria
facility: LKH Steyr
city: Wien
country: Austria
facility: Medizinische Universität Wien, Allgemeines Krankenhaus der Stadt Wien
city: Wien
country: Austria
facility: Hanusch-Krankenhaus
city: Creteil
country: France
facility: CHU Henri Mondor; Service d'Oncologie Medicale
city: Lyon
country: France
facility: Centre Leon Berard
city: Paris
country: France
facility: Hôpital Saint-Louis
city: Saint Herblain
country: France
facility: Centre Henri Becquerel- Centre de Lutte Contre le Cancer
city: Villejuif
country: France
facility: Gustave Roussy
city: Gyeongsangnam-do
country: Korea, Republic of
facility: Pusan National University Yangsan Hospital
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Gliwice
country: Poland
facility: Maria Sklodowska-Curie Memorial Cancer Centre
city: Kraków
country: Poland
facility: Ma?opolskie Centrum Medyczne
city: Slupsk
country: Poland
facility: Wojewodzki Szpital Specjalistyczny im. Janusza Korczaka
city: Warsaw
country: Poland
facility: Instytut Hematologii i Transfuzjologii; Klinika Zaburze? Hemostazy i Chorób Wewn?trznych
city: Wroc?aw
country: Poland
facility: Katedra i Klinika Hematologii; Nowotworów Krwi i Transplantacji Szpiku
city: Badalona
country: Spain
facility: Institut Catala d?Oncologia Hospital Germans Trias i Pujol
state: Barcelona
city: Pamplona
country: Spain
facility: Clinica Universidad de Navarra
state: Navarra
city: Seville
country: Spain
facility: Hospital Universitario Virgen Macarena
state: Sevilla
city: Barcelona
country: Spain
facility: Hospital de la Santa Creu i Sant Pau
city: Caceres
country: Spain
facility: Hospital San Pedro de Alcantara; Servicio de Hematología
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Marañon
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Madrid
country: Spain
facility: Hospital Universitario La Paz
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: