Clinical trial NCT05171647: A Study Evaluating Efficacy and Safety of Mosunetuzumab in Combination With Polatuzumab Vedotin Compared to Rituximab in Combination With Gemcitabine Plus Oxaliplatin in Participants With Relapsed or Refractory Aggressive B-Cell Non-Hodgkin's Lymphoma
Official title: A Randomized, Open-Label, Multicenter Phase III Study Evaluating Efficacy and Safety of Mosunetuzumab in Combination With Polatuzumab Vedotin in Comparison With Rituximab in Combination With Gemcitabine Plus Oxaliplatin in Participants With Relapsed or Refractory Aggressive B-Cell Non-Hodgkin's Lymphoma
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Non-Hodgkin Lymphoma
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2021-12-29
Enrollment: 242
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 assess the efficacy and safety of mosunetuzumab in combination with polatuzumab vedotin (M+P) in participants with relapsed or refractory (R/R) diffuse-large B-cell lymphoma (DLBCL), high-grade B-cell lymphoma, transformed follicular lymphoma (trFL) and FL Grade 3B (FL3B) in comparison with a commonly used regimen in this participant population, rituximab, gemcitabine and oxaliplatin (R-GemOx).


Eligibility criteria: Inclusion Criteria:

* Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1, or 2
* CD20+ aggressive lymphoma as determined by the local hemopathology laboratory from the following diagnoses by 2016 World Health Organization classification of lymphoid neoplasms: DLBCL, not otherwise specified (NOS); high-grade B-cell lymphoma (NOS or double/triple hit); transformed follicular lymphoma; follicular lymphoma Grade 3b
* Have disease relapsed or refractory to at least one prior systemic therapy for aggressive non-Hodgkin's lymphoma (aNHL)
* Participants who have received only one prior line of therapy must be ineligible for autologous stem cell transplant (ASCT)
* Measurable disease
* Adequate hepatic, hematologic, and renal function
* Estimated creatinine clearance (CrCl) ≥ 30 mL/min by Cockroft-Gault method or other institutional standard methods
* Negative HIV test at screening. Participants with a positive HIV test at screening are eligible provided that, prior to enrollment, they are stable on anti-retroviral therapy for at least 4 weeks, have a CD4 count of at least 200 microliters, have an undetectable viral load, and have not had a history of opportunistic infection attributable to AIDS within the last 12 months

Exclusion Criteria:

* Pregnant or breast feeding, or intending to become pregnant during the study or within 3 months after the final dose of mosunetuzumab, 9 months after the final dose of polatuzumab vedotin, 12 months after the final dose of rituximab, 6 months after the final dose of gemcitabine, 9 months after the final dose of oxaliplatin, and 3 months after the final dose of tocilizumab, as applicable
* Inability to comply with protocol-mandated activity restrictions
* Prior treatment with mosunetuzumab or other CD-20-directed bispecific antibodies, or R-GemOx or Gem-Ox
* Prior treatment with polatuzumab vedotin, with the following exceptions: participants who have a documented response (partial response or complete response) to polatuzumab vedotin and an absence of PD within 12 months from the last dose of polatuzumab vedotin; participants who received up to 2 doses of a polatuzumab vedotin-containing regimen as bridging to CAR-T therapy, and either has a documented disease control (stable disease, partial response, or complete response), or were not assessed for response following treatment with polatuzumab vedotin
* Contraindication to any component of the study treatment
* Grade \> 1 peripheral neuropathy
* Participants with Grade \> 1 persistent toxicity related to prior anti-lymphoma treatment (except for alopecia and anorexia, or other toxicities not considered a safety risk for the participant per investigator's judgment)
* Received anti-lymphoma treatments with monoclonal antibodies, radio-immunoconjugates or antibody-drug conjugates (ADCs) within 4 weeks before the first dose of study treatment
* Treatment with any chemotherapeutic agent, or treatment with any other anti-lymphoma agent (investigational or otherwise) within 4 weeks or 5 half-lives of the drug, whichever is shorter, prior to the first dose of study treatment
* Treatment with radiotherapy within 2 weeks prior to the first dose of study treatment
* ASCT within 100 days prior to the first study treatment administration
* Prior treatment with chimeric antigen receptor (CAR) T cell therapy within 30 days before the first study treatment administration
* Prior allogenic stem cell transplant (SCT)
* Have had a solid organ transplantation
* Known or suspected history of hemophagocytic lymphohistiocytosis (HLH)
* History of confirmed progressive multifocal leukoencephalopathy
* History of severe allergic or anaphylactic reactions to monoclonal antibody therapy (or recombination antibody-related fusion proteins)
* History of other malignancy that could affect compliance with the protocol or interpretation of results, with the exception of malignancies with a negligible risk of metastasis or death
* Currently have or have had a past history of central nervous system (CNS) involvement of lymphoma
* Current or past history of CNS disease, such as stroke, epilepsy, CNS vasculitis, or neurodegenerative disease. Participants with a history of stroke who have not experienced a stroke or transient ischemic attack in the past 2 years and have no residual neurologic deficits as judged by the investigator, or with a history of epilepsy who have had no seizures in the past 2 years while not receiving any anti-epileptic medications, are allowed
* Significant cardiovascular disease such as New York Heart Association Class III or IV cardiac disease, myocardial infarction within the last 6 months, unstable arrhythmias, or unstable angina
* Significant active pulmonary disease
* Participants with active symptoms of interstitial lung disease and/or pneumonitis, or those with a history of interstitial lung disease and/or pneumonitis within 6 months prior to the first dose of study treatment
* Known active bacterial, viral, fungal, mycobacterial, parasitic, or other infection (excluding fungal infections of the nail beds) at study enrollment, or any major episode of infection requiring treatment with IV antibiotics or hospitalization (relating to the completion of the course of antibiotics) within 2 weeks prior to the first study treatment administration
* Known or suspected chronic active Epstein-Barr virus (EBV) infection
* Recent major surgery within 4 weeks prior to the first study treatment administration
* Positive test results for chronic hepatitis B infection
* Acute or chronic hepatitis C virus (HCV) infection
* Have been administered a live, attenuated vaccine within 4 weeks before the first dose of study treatment administration or anticipation that such a live, attenuated vaccine will be required during the study
* Participants who have positive SARS-CoV-2 test within 7 days prior to enrollment (rapid antigen test result is acceptable)
* History of autoimmune disease
* Received investigational therapy, whether or not intended for lymphoma treatment, within 7 days prior to initiation of study treatment
* Clinically significant history of liver disease, including viral or other hepatitis, or cirrhosis

Primary outcomes:
measure: Progression-free survival (PFS)
timeFrame: From randomization to the first occurrence of disease progression as determined by an independent review facility (IRF), or death due to any cause, whichever occurs first (up to 2.5 years)
measure: Objective response rate (ORR) as determined by an independent review facility (IRF)
timeFrame: Up to 2.5 years
Secondary outcomes:
measure: ORR as determined by the investigator
timeFrame: Up to 2.5 years
measure: Duration of response (DOR)
timeFrame: The time from the first occurrence of a documented objective response to disease progression or death from any cause, whichever occurs first, as determined by the investigator and IRF (up to 2.5 years)
measure: Overall survival (OS)
timeFrame: From randomization to death from any cause (up to 2.5 years)
measure: PFS
timeFrame: From randomization to the first occurrence of disease progression as determined by the investigator, or death due to any cause, whichever occurs first (up to 2.5 years)
measure: Complete response rate (CRR)
timeFrame: Up to 2.5 years
measure: Duration of complete response (DOCR)
timeFrame: From the first occurrence of a documented complete response (CR) to disease progression or death from any cause, whichever occurs first, as determined by IRF and the investigator (up to 2.5 years)
measure: Time to deterioration in physical functioning and fatigue as measured by the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30
timeFrame: Up to 2.5 years
measure: Time to deterioration in lymphoma symptoms as measured by the functional assessment of cancer therapy lymphoma subscale (FACT-Lym LymS)
timeFrame: Up to 2.5 years
measure: Incidence of adverse events (AEs)
timeFrame: Up to 2.5 years
measure: Change from baseline in peripheral neuropathy as measured by the functional assessment of cancer therapy/gynecologic oncology group - neurotoxicity (FACT/GOG-NTX)
timeFrame: Up to 2.5 years
measure: Serum concentration of mosunetuzumab
timeFrame: Up to 2.5 years
measure: Plasma concentration of polatuzumab vedotin
timeFrame: Up to 2.5 years
measure: Change from baseline in the EuroQol 5-dimension, 5-level questionnaire (EuroQol EQ 5D-5L) index-based scores
timeFrame: Up to 2.5 years
measure: Change from baseline in the EuroQol EQ 5D-5L visual analog scale (VAS) scores
timeFrame: Up to 2.5 years
measure: Incidence of anti-drug antibodies (ADAs) to mosunetuzumab
timeFrame: Up to 2.5 years
measure: Incidence of anti-drug antibodies (ADAs) to polatuzumab vedotin
timeFrame: Up to 2.5 years
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope Cancer Center
state: California
city: Chesterfield
country: United States
facility: St. Luke's Hospital
state: Missouri
city: Austin
country: United States
facility: Ascension Seton Infusion Center
state: Texas
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: Buenos Aires
country: Argentina
facility: Hospital Aleman
city: Buenos Aires
country: Argentina
facility: Instituto Alexander Fleming
city: Buenos Aires
country: Argentina
facility: FUNDALEU
city: Ciudad Autonoma Buenos Aires
country: Argentina
facility: Hospital Italiano de Buenos Aires
city: Curitiba
country: Brazil
facility: Hospital Erasto Gaertner
state: Paraná
city: Porto Alegre
country: Brazil
facility: Hospital das Clinicas - UFRGS
state: Rio Grande Do Sul
city: Ribeirao Preto
country: Brazil
facility: Hospital das Clínicas FMRP-USP
state: São Paulo
city: Sao Paulo
country: Brazil
facility: Hospital Sao Jose
state: São Paulo
city: São Paulo
country: Brazil
facility: D'or Instituto de Pesquisa e Educação
city: Hamilton
country: Canada
facility: Hamilton Health Sciences - Juravinski Cancer Centre
state: Ontario
city: Toronto
country: Canada
facility: Princess Margaret Hospital
state: Ontario
city: Montreal
country: Canada
facility: Chum Hopital Notre Dame
state: Quebec
city: Chengdu City
country: China
facility: Sichuan Cancer Hospital
city: Fuzhou City
country: China
facility: Fujian Medical University Union Hospital
city: Guangzhou City
country: China
facility: Cancer Center, Sun Yat-sen University of Medical Sciences
city: Tianjin
country: China
facility: Tianjin Cancer Hospital
city: Wuhan
country: China
facility: Tongji Hosp, Tongji Med. Col, Huazhong Univ. of Sci. & Tech
city: Zhengzhou
country: China
facility: Henan Cancer Hospital
city: Beer Sheva
country: Israel
facility: Soroka Medical Center
city: Tel Aviv
country: Israel
facility: Ichilov Sourasky Medical Center
city: Fukuoka
country: Japan
facility: Kyushu University Hospital
city: Hokkaido
country: Japan
facility: Hokkaido University Hospital
city: Miyagi
country: Japan
facility: Tohoku University Hospital
city: Osaka
country: Japan
facility: Kindai University Hospital
city: Tokyo
country: Japan
facility: The Cancer Institute Hospital of JFCR
city: Yamagata
country: Japan
facility: Yamagata University Hospital
city: Busan
country: Korea, Republic of
facility: Pusan National University Hospital
city: Daejeon
country: Korea, Republic of
facility: Chungnam National University Hospital
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: Samsung Medical Center
city: Seoul
country: Korea, Republic of
facility: Yeouido St. Mary's Hospital
city: Cdmx
country: Mexico
facility: Health Pharma Professional Research
state: Mexico CITY (federal District)
city: Ciudad de México
country: Mexico
facility: Superare Centro de Infusion S.A. de C.V.
state: Mexico CITY (federal District)
city: Monterrey
country: Mexico
facility: Hospital Universitario Dr. Jose E. Gonzalez
state: Nuevo LEON
city: Distrito Federal
country: Mexico
facility: Instituto Nacional de Cancerologia
city: Mexico
country: Mexico
facility: Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
city: Auckland
country: New Zealand
facility: Middlemore Clinical Trials
city: Arequipa
country: Peru
facility: Instituto Regional de Enfermedades Neoplásicas del Sur
city: Lima
country: Peru
facility: Oncosalud Sac
city: Bangkok
country: Thailand
facility: Chulalongkorn University Hospital
city: Bangkok
country: Thailand
facility: Siriraj Hospital
city: Chiang Mai
country: Thailand
facility: Chiang Mai Uni Hospital
city: Khon Kaen
country: Thailand
facility: Srinagarind Hospital, Khon Kaen Uni
city: Ankara
country: Turkey
facility: Ankara University Medical Faculty
city: Istanbul
country: Turkey
facility: Medipol Mega Üniversite Hastanesi Göztepe
city: Kocaeli
country: Turkey
facility: Anadolu Health Center
city: Lzmir
country: Turkey
facility: Dokuz Eylul Universitesi Tip Fakultesi
city: Samsun
country: Turkey
facility: Ondokuz Mayis Univ. Med. Fac.
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: