Clinical trial NCT04712097: A Study Evaluating the Efficacy and Safety of Mosunetuzumab in Combination With Lenalidomide in Comparison to Rituximab in Combination With Lenalidomide With a US Extension of Mosunetuzumab in Combination With Lenalidomide in Participants With Follicular Lymphoma
Official title: Phase III Randomized, Open-Label, Multicenter Study Evaluating Efficacy and Safety of Mosunetuzumab in Combination With Lenalidomide in Comparison to Rituximab in Combination With Lenalidomide With a Non-Randomized Single Arm US Extension of Mosunetuzumab in Combination With Lenalidomide in Patients With Follicular Lymphoma After at Least One Line of Systemic Therapy
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Relapsed or Refractory Follicular Lymphoma
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2021-01-15
Enrollment: 478
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 efficacy and safety of mosunetuzumab in combination with lenalidomide (M + Len) compared to rituximab in combination with lenalidomide (R + Len) in participants with relapsed or refractory (R/R) follicular lymphoma (FL) who have received at least one line of prior systemic therapy.


Eligibility criteria: Inclusion Criteria:

* Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1, or 2
* Histologically documented CD20+ FL (Grades 1-3a)
* Requiring systemic therapy assessed by investigator based on tumor size and/or Groupe d'Etude des Lymphomes Folliculaires (GELF) criteria
* Received at least one prior systemic lymphoma therapy, which included prior immunotherapy or chemoimmunotherapy
* Availability of a representative tumor specimen and the corresponding pathology report at the time of relapse/persistence for confirmation of the diagnosis of FL. Pretreatment sample of at least 1 core-needle, excisional or incisional tumor biopsy is required. Cytological or fine-needle aspiration samples are not acceptable. Fresh pretreatment biopsy is preferred. Patients who are unable to undergo biopsy procedures may be eligible for study enrollment if an archival tumor tissue sample (preferably from the most recent relapse/persistence) as paraffin blocks or at least 15 unstained slides, or in accordance with local regulatory requirements, can be sent to the Sponsor.
* Adequate hematologic function (unless due to underlying lymphoma, per the investigator)
* Agreement to comply with all local requirements of the lenalidomide risk minimization plan, which includes the global pregnancy prevention program.
* For women of childbearing potential: Agreement to remain abstinent (refrain from heterosexual intercourse) or use 2 adequate methods of contraception, including at least 1 method with a failure rate of \< 1% per year, for at least 28 days prior to Day 1 of Cycle 1, during the treatment period (including periods of treatment interruption), and for at least 28 days after the last dose of lenalidomide, 3 months after the final dose of tocilizumab (if applicable), mosunetuzumab, and 12 months after final dose of rituximab. Women must refrain from donating eggs during this same period.
* For men: Agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures and agreement to refrain from donating sperm, as defined: With female partners of childbearing potential or pregnant female partners, men must remain abstinent or use a condom during the treatment period and for at least 28 days after last dose of lenalidomide, 3 months after the final dose of tocilizumab (if applicable), mosunetuzumab and 12 months after the final dose of rituximab. Men must refrain from donating sperm during this same period.

Exclusion Criteria:

* Grade 3b FL
* Any history of disease transformation and/or diffuse-large B cell lymphoma (DLBCL)
* Documented refractoriness to lenalidomide, defined as no response (partial response or complete response) or relapse within 6 months of therapy
* Active or history of CNS lymphoma or leptomeningeal infiltration
* Prior standard or investigational anti-cancer therapy as specified: Lenalidomide exposure within 12 months prior to Day 1 of Cycle 1; Chimeric antigen receptor T cell therapy within 30 days prior to Day 1 of Cycle 1; Radioimmunoconjugate within 12 weeks prior to Day 1 of Cycle 1; Monoclonal antibody or antibody-drug conjugate within 4 weeks prior to Cycle 1 Day 1; Treatment with any 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
* Clinically significant toxicity (other than alopecia) from prior treatment that has not resolved to Grade \</= 1 (per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), Version 5.0) prior to Day 1 of Cycle 1
* Treatment with systemic immunosuppressive medications, including, but not limited to prednisone (\> 20 mg), azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor agents within 2 weeks prior to Day 1 of Cycle 1
* History of solid organ transplantation
* History of severe allergic or anaphylactic reaction to humanized, chimeric or murine monoclonal antibodies
* Known sensitivity or allergy to murine products
* Known hypersensitivity to biopharmaceuticals produced in Chinese hamster ovary (CHO) cells or any component of the mosunetuzumab, rituximab, tocilizumab, lenalidomide, or thalidomide formulation, including mannitol
* History of erythema multiforme, Grade \>/= 3 rash, or blistering following prior treatment with immunomodulatory derivatives
* History of interstitial lung disease, drug-induced pneumonitis, and autoimmune pneumonitis
* Known active bacterial, viral, fungal, or other infection, or any major episode of infection requiring treatment with IV antibiotics within 4 weeks of Day 1 of Cycle 1
* Known or suspected chronic active Epstein-Barr virus (EBV) infection
* Known or suspected history of hemophagocytic lymphohistiocytosis
* Clinically significant history of liver disease, including viral or other hepatitis, or cirrhosis
* Active Hepatitis B infection
* Active Hepatitis C infection
* Known history of HIV positive status
* History of progressive multifocal leukoencephalopathy (PML)
* Administration of a live, attenuated vaccine within 4 weeks before first dose of study treatment or anticipation that such a live attenuated vaccine will be required during the study
* Other malignancy that could affect compliance with the protocol or interpretation of results
* Active autoimmune disease requiring treatment
* History of autoimmune disease, including, but not limited to: myocarditis, pneumonitis, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjögren's syndrome, Guillain-Barré syndrome, multiple sclerosis, vasculitis, or glomerulonephritis
* Prior allogeneic stem cell transplantation
* Contraindication to treatment for thromboembolism prophylaxis
* Evidence of any significant, uncontrolled concomitant disease that could affect compliance with the protocol or interpretation of results, including, but not limited to, significant cardiovascular disease (e.g., New York Heart Association Class III or IV cardiac disease, myocardial infarction within the previous 6 months, unstable arrhythmia, or unstable angina) or significant pulmonary disease (such as obstructive pulmonary disease or history of bronchospasm)
* Major surgical procedure other than for diagnosis within 28 days prior to Day 1 of Cycle 1 Day 1 or anticipation of a major surgical procedure during the course of the study
* Pregnant or lactating or intending to become pregnant during the study
* Any serious medical condition or abnormality in clinical laboratory tests that, in the investigator's judgment, precludes the patient's safe participation in and completion of the study, or which could affect compliance with the protocol or interpretation of results

Primary outcomes:
measure: Progression Free Survival (PFS) according to 2014 Lugano Response Criteria
timeFrame: From randomization to the first occurrence of disease progression as determined by an independent review committee (IRC) or death from any cause (up to approximately 8.5 years)
Secondary outcomes:
measure: PFS as Determined by the Investigator
timeFrame: From randomization to the first occurrence of disease progression or death from any cause (up to approximately 8.5 years)
measure: Complete Response Rate
timeFrame: Up to approximately 8.5 years
measure: Objective Response Rate (ORR)
timeFrame: Up to approximately 8.5 years
measure: Overall Survival (OS)
timeFrame: From randomization to death from any cause (up to approximately 8.5 years)
measure: Duration of Objective Response (DOR)
timeFrame: From the first occurrence of a documented objective response (complete response or partial response) to disease progression or death from any cause, whichever occurs first (up to approximately 8.5 years)
measure: Duration of Complete Reponse (DOCR)
timeFrame: From the first occurrence of a documented CR to disease progression or death from any cause, whichever occurs first (up to approximately 8.5 years)
measure: Time to Deterioration in Physical Functioning and Fatigue, as Measured by the European Organisation for Research and Treatment of Cancer Quality of Life-Core 30 Questionnaire (EORTC QLQ-C30)
timeFrame: Up to approximately 8.5 years
measure: Time to Deterioration in Lymphoma Symptoms, as Measured by the Functional Assessment of Cancer Therapy-Lymphoma Subscale (FACT-LymS)
timeFrame: Up to approximately 8.5 years
measure: Percentage of Participants with Adverse Events (AEs)
timeFrame: Up to approximately 8.5 years
measure: Serum Concentration of M + Len
timeFrame: Up to approximately 8.5 years
measure: Area Under the Curve (AUC) of M + Len
timeFrame: Up to approximately 8.5 years
measure: Percentage of Participants with Anti-Drug Antibodies (ADAs)
timeFrame: Up to approximately 8.5 years
measure: Time to New Anti-Lymphoma Treatment (TTNALT)
timeFrame: From randomization to the first documented administration of a new anti-lymphoma treatment (up to approximately 8.5 years)
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope Comprehensive Cancer Center
state: California
city: Atlanta
country: United States
facility: Winship Cancer Institute
state: Georgia
city: Fort Wayne
country: United States
facility: Fort Wayne Medical Oncology and Hematology, Inc
state: Indiana
city: Noblesville
country: United States
facility: Investigative Clinical Research of Indiana, LLC
state: Indiana
city: Baltimore
country: United States
facility: Johns Hopkins Uni
state: Maryland
city: Ann Arbor
country: United States
facility: University of Michigan Health System
state: Michigan
city: Grand Rapids
country: United States
facility: Cancer & Hematology Center of West Michigan
state: Michigan
city: Saint Louis
country: United States
facility: Washington University
state: Missouri
city: Bronx
country: United States
facility: Montefiore Medical Center - Montefiore Medical Park
state: New York
city: Bronx
country: United States
facility: Montefiore Medical Center
state: New York
city: Mineola
country: United States
facility: NYU Long Island Hospital
state: New York
city: New York
country: United States
facility: NYU Langone Ambulatory Care Center
state: New York
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest Univ Health Svcs
state: North Carolina
city: Dallas
country: United States
facility: Baylor University Medical Center
state: Texas
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: Kennewick
country: United States
facility: Kadlec Clinic Hematology and Oncology
state: Washington
city: Waratah
country: Australia
facility: Calvary Mater Newcastle
state: New South Wales
city: Woolloongabba
country: Australia
facility: Princess Alexandra Hospital Woolloongabba
state: Queensland
city: Adelaide
country: Australia
facility: Royal Adelaide Hospital
state: South Australia
city: Geelong
country: Australia
facility: Geelong Hospital
state: Victoria
city: Curitiba
country: Brazil
facility: ICTR Curitiba
state: Paraná
city: Porto Alegre
country: Brazil
facility: Hospital das Clinicas - UFRGS
state: Rio Grande Do Sul
city: Porto Alegre
country: Brazil
facility: Hospital Mae de Deus
state: Rio Grande Do Sul
city: Sao Paulo
country: Brazil
facility: Hospital Alemao Oswaldo Cruz
state: São Paulo
city: Beijing City
country: China
facility: Peking University First Hospital
city: Beijing
country: China
facility: Beijing Cancer Hospital
city: Beijing
country: China
facility: Peking University Third Hospital
city: Changchun City
country: China
facility: The First Hospital of Jilin University
city: Guangzhou
country: China
facility: Cancer Center, Sun Yat-sen University of Medical Sciences
city: Harbin
country: China
facility: Harbin Medical University Cancer Hospital
city: Nanchang City
country: China
facility: The 1st Affiliated Hospital of Nanchang Unversity
city: Nanjing
country: China
facility: Jiangsu Province Hospital
city: Shanghai
country: China
facility: Fudan University Shanghai Cancer Center
city: Shanghai
country: China
facility: Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine
city: Tianjin City
country: China
facility: Institute of Hematology and Blood Diseases Hospital Chinese Academy of Medical Sciences
city: Wuhan City
country: China
facility: Union Hospital Tongji Medical College Huazhong University of Science and Technology
city: Wuhan City
country: China
facility: Tongji Hospital Tongji Medical College Huazhong University of Science and Technology
city: Xiamen
country: China
facility: The First Affiliated Hospital of Xiamen University
city: Zhejiang
country: China
facility: Zhejiang Cancer Hospital
city: Zhengzhou
country: China
facility: The First Affiliated Hospital of Zhengzhou University
city: Bayonne
country: France
facility: Centre Hospitalier de La Cote Basque
city: Chambery
country: France
facility: Ch De Chambery
city: Creteil
country: France
facility: Hopital Henri Mondor
city: Lille
country: France
facility: Hopital Claude Huriez
city: Marseille
country: France
facility: Institut Paoli Calmettes
city: Montpellier
country: France
facility: CHU Saint Eloi
city: Nantes
country: France
facility: CHU NANTES - Hôtel Dieu
city: Nice
country: France
facility: Centre Antoine Lacassagne
city: Nimes
country: France
facility: CHU de Nîmes - Hôpital Carémeau
city: Paris
country: France
facility: Hôpital Saint-Louis
city: Paris
country: France
facility: Hopital Saint Antoine
city: Pessac
country: France
facility: Hopital De Haut Leveque
city: Pierre Benite
country: France
facility: Ch Lyon Sud
city: Poitiers
country: France
facility: Hopital De La Miletrie
city: Reims
country: France
facility: CHU de Reims
city: Rennes
country: France
facility: CHU Pontchaillou
city: Rouen
country: France
facility: Centre Henri Becquerel
city: Strasbourg
country: France
facility: ICANS
city: Berlin
country: Germany
facility: Vivantes Klinikum Am Urban Klinik für Innere Medizin Hämatologie und Onkologie
city: Dresden
country: Germany
facility: BAG Freiberg-Richter, Jacobasch, Illmer, Wolf
city: Halle (Saale)
country: Germany
facility: Universitätsklinikum Halle
city: Heidelberg
country: Germany
facility: Uniklinik Heidelberg, Medizinische Klinik & Poliklinik V
city: Regensburg
country: Germany
facility: Klinik und Poliklinik f. Innere Medizin III des Universitätsklinikums Regensburg
city: Rostock
country: Germany
facility: Universitätsklinik Rostock
city: Ulm
country: Germany
facility: Universtitätsklinikum Ulm
city: Bologna
country: Italy
facility: A.O. Universitaria Policlinico S.Orsola-Malpighi Di Bologna
state: Emilia-Romagna
city: Ravenna
country: Italy
facility: U.O. Ematologia AUSL Ravenna
state: Emilia-Romagna
city: Ancona
country: Italy
facility: Ospedali Riuniti Umberto I
state: Marche
city: Palermo
country: Italy
facility: Ospedale V. Cervello
state: Sicilia
city: Firenze
country: Italy
facility: Azienda Ospedaliera Universitaria Careggi
state: Toscana
city: Padova
country: Italy
facility: Ematologia/immunologia Clinica Azienda Ospedaliera Policlinico di Padova
state: Veneto
city: Aichi
country: Japan
facility: Aichi Cancer Center
city: Chiba
country: Japan
facility: National Cancer Center Hospital East
city: Kyoto
country: Japan
facility: University Hospital Kyoto Prefectural University of Medicine
city: Mie
country: Japan
facility: Mie University Hospital
city: Miyagi
country: Japan
facility: Tohoku University Hospital
city: Okayama
country: Japan
facility: Okayama University Hospital
city: Tokyo
country: Japan
facility: National Cancer Center Hospital
city: Tokyo
country: Japan
facility: The Cancer Institute Hospital of JFCR
city: Busan
country: Korea, Republic of
facility: Pusan National University Hospital
city: Seongnam-si
country: Korea, Republic of
facility: Seoul National University Bundang Hospital
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Severance Hospital, Yonsei University Health System
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Seoul St Mary's Hospital
city: Gdansk
country: Poland
facility: Uniwersyteckie Centrum Kliniczne
city: Gdynia
country: Poland
facility: Szpitale Pomorskie Sp. z o. o.
city: Katowice
country: Poland
facility: Pratia Onkologia Katowice
city: Pozna?
country: Poland
facility: Uniwersytecki Szpital Kliniczny w Poznaniu
city: Warszawa
country: Poland
facility: Instytut Hematologii i Transfuzjologii
city: Wroc?aw
country: Poland
facility: Uniwersytecki Szpital Kliniczny im. Jana Mikulicza-Radeckiego we Wroclawiu
city: Moscow
country: Russian Federation
facility: City Clinical Botkin's Hospital
city: Penza
country: Russian Federation
facility: Penza Regional Oncology Dispensary
city: Guipuzcoa
country: Spain
facility: Hospital de Donostia
city: Madrid
country: Spain
facility: Hospital Universitario la Paz
city: Murcia
country: Spain
facility: Hospital General Universitario J.M Morales Meseguer
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocio
city: Valencia
country: Spain
facility: Hospital Clinico Universitario de Valencia
city: Kaoisung
country: Taiwan
facility: Chang Gung Medical Foundation - Kaohsiung;Oncology
city: Taipei City
country: Taiwan
facility: Taipei Veterans General Hospital
city: Taipei
country: Taiwan
facility: National Taiwan Universtiy Hospital
city: Taoyuan
country: Taiwan
facility: Chang Gung Medical Foundation - Linkou
city: Ankara
country: Turkey
facility: Hacettepe Uni Medical Faculty
city: Istanbul
country: Turkey
facility: Atakent Acibadem Private Hosptial Halkali Merkez Mh.,
city: Istanbul
country: Turkey
facility: Marmara Ün?Vers?Tes? ?Stanbul Pend?K E??T?M Ve Ara?Tirma Hastanes?
city: Sariyer
country: Turkey
facility: Koc Universitesi (KU) Tip Fakultesi (Koc University School of Medicine)
city: Cornwall
country: United Kingdom
facility: Royal Cornwall Hospitals NHS Trust
city: Gloucester
country: United Kingdom
facility: Gloucestershire Royal Hospital
city: London
country: United Kingdom
facility: Hammersmith Hospital
city: Nottingham
country: United Kingdom
facility: Nottingham City Hospital
city: Torquay
country: United Kingdom
facility: Torbay Hospital
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: