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

Non-Hodgkin Lymphoma Clinical Trial

— SUNMO  

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05171647
• Other study ID #: GO43643
• Status: Recruiting
• Phase: Phase 3
• Start date: April 25, 2022
• Est. completion date: November 30, 2027

Study information

• Verified date: June 2024
• Source: Hoffmann-La Roche
• Contact: Reference Study ID number: GO43643 https://forpatients.roche.com
• Phone: 888-662-6728
• Email: global-roche-genentech-trials[@]gene.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 222
• Est. completion date: November 30, 2027
• Est. primary completion date: May 30, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Lymphoma
• Lymphoma, B-Cell
• Lymphoma, Non-Hodgkin
• Non-Hodgkin Lymphoma

Intervention

Drug:
• Mosunetuzumab
Participants will receive SC mosunetuzumab on Days 1, 8, and 15 of Cycle 1, and on Day 1 of Cycles 2-8 (cycle length = 21 days).
• Polatuzumab vedotin
Participants will receive IV polatuzumab vedotin every three weeks (Q3W) for 6 cycles (cycle length = 21 days).
• Tocilizumab
Participants will receive IV tocilizumab as needed to manage cytokine release syndrome (CRS) events.
• Rituximab
Participants will receive IV rituximab on Day 1 of each cycle for 8 cycles (cycle length = 14 days).
• Gemcitabine
Participants will receive IV gemcitabine on Day 1 of each cycle for 8 cycles (cycle length = 14 days).
• Oxaliplatin
Participants will receive IV oxaliplatin on Day 1 of each cycle for 8 cycles (cycle length = 14 days).

Locations

Country	Name	City	State
Argentina	Fundaleu; Haematology	Buenos Aires
Argentina	Instituto Alexander Fleming	Buenos Aires
Argentina	Hospital Aleman	Ciudad Autonoma Buenos Aires
Argentina	Hospital Italiano de Buenos Aires	Ciudad Autónoma de Buenos Aires
Brazil	Hospital Erasto Gaertner	Curitiba	PR
Brazil	Hospital das Clinicas - UFRGS	Porto Alegre	RS
Brazil	Hospital das Clínicas FMRP-USP	Ribeirao Preto	SP
Brazil	D'or Instituto de Pesquisa e Educação	Sao Paulo	SP
Brazil	Hospital Sao Jose	Sao Paulo	SP
Canada	Hamilton Health Sciences - Juravinski Cancer Centre	Hamilton	Ontario
Canada	Chum Hopital Notre Dame; Centre D'Oncologie	Montreal	Quebec
Canada	Saskatchewan Cancer Agency (SCA) - Saskatoon Cancer Centre (SCC)	Saskatoon	Saskatchewan
Canada	Princess Margaret Hospital; Department of Med Oncology	Toronto	Ontario
China	Sichuan Cancer Hospital	Chengdu City
China	Fujian Medical University Union Hospital	Fuzhou City
China	Cancer Center, Sun Yat-sen University of Medical Sciences; Department of Medical Oncology	Guangzhou City
China	The First Affiliated Hospital of College of Medicine, Zhejiang University	Hangzhou
China	The Second Affiliated Hospital to Nanchang University	Nanchang
China	Tianjin Cancer Hospital	Tianjin
China	Tongji Hosp, Tongji Med. Col, Huazhong Univ. of Sci. & Tech	Wuhan
China	Henan Cancer Hospital	Zhengzhou
Israel	Soroka Medical Center; Hematology Deptartment	Beer Sheva
Israel	Meir Medical Center; Heamatology Dept	Kfar Saba
Israel	Ichilov Sourasky Medical Center; Heamatology	Tel Aviv
Japan	Kyushu University Hospital	Fukuoka
Japan	Hokkaido University Hospital	Hokkaido
Japan	Kobe City Medical Center General Hospital	Hyogo
Japan	Tokai University Hospital	Kanagawa
Japan	Mie University Hospital	Mie
Japan	Tohoku University Hospital	Miyagi
Japan	Kindai University Hospital	Osaka
Japan	The Cancer Institute Hospital of JFCR	Tokyo
Japan	Yamagata University Hospital	Yamagata
Korea, Republic of	Pusan National University Hospital	Busan
Korea, Republic of	Chungnam National University Hospital	Daejeon
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
Korea, Republic of	Severance Hospital, Yonsei University Health System	Seoul
Korea, Republic of	Yeouido St. Mary's Hospital	Seoul
Mexico	Health Pharma Professional Research	Cdmx	Mexico CITY (federal District)
Mexico	Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran	Mexico
Mexico	Superare Centro de Infusion S.A. de C.V.	Mexico	Mexico CITY (federal District)
Mexico	Instituto Nacional de Cancerologia; Oncology	Mexico City
Mexico	Hospital Universitario Dr. Jose E. Gonzalez; Haematology	Monterrey	Nuevo LEON
New Zealand	Middlemore Clinical Trials	Auckland
Peru	Instituto Regional de Enfermedades Neoplásicas del Sur; Centro de Inv. de Medicina Oncológica	Arequipa
Peru	Hospital Nacional Edgardo Rebagliati Martins, Servicio de Gastroenterologia	Lima
Peru	Instituto Nacional de Enfermedades Neoplasicas	Lima
Peru	Oncosalud Sac; Oncología	Lima
Peru	Hospital De Alta Complejidad Virgen De La Puerta - Essalud; Oncology	Trujillo
Russian Federation	Regional Clinical Hospital N.A. Semashko; Hematology	Nizhny Novgorod	Niznij Novgorod
Russian Federation	Penza Regional Oncology Dispensary	Penza
Thailand	Chulalongkorn University Hospital; Hematology	Bangkok
Thailand	Siriraj Hospital; Division of Hematology, Department of Medicine	Bangkok
Thailand	Chiang Mai Uni Hospital; Division of Hematology,Dept of Medicine,Faculty of Medicine	Chiang Mai
Thailand	Srinagarind Hospital, Khon Kaen Uni ; Dept of Medicine	Khon Kaen
Turkey	Ankara University Medical Faculty	Ankara
Turkey	Medipol Mega Üniversite Hastanesi Göztepe	Istanbul
Turkey	Anadolu Health Center; Heamathology Department	Kocaeli
Turkey	Dokuz Eylul Universitesi Tip Fakultesi	Lzmir
Turkey	Ondokuz Mayis Univ. Med. Fac.	Samsun
United States	Alaska Oncology & Hematology, LLC	Anchorage	Alaska
United States	Ascension Seton Infusion Center	Austin	Texas
United States	Levine Cancer Institute - Clincal Trials Administration	Charlotte	North Carolina
United States	St. Luke's Hospital	Chesterfield	Missouri
United States	City of Hope Cancer Center; Division of Medical Oncology & Experimental Therapeutics	Duarte	California
United States	MD Anderson Cancer Center	Houston	Texas
United States	Kaiser Permanente - Irvine	Irvine	California
United States	Cancer Blood and Specialty Clinic	Los Alamitos	California
United States	USC School of Medicine	Los Angeles	California
United States	University of Miami - Clinical Research Services	Miami	Florida
United States	Investigative Clinical Research of Indiana, LLC	Noblesville	Indiana
United States	Rhode Island Hospital; Comprehensive Cancer Center	Providence	Rhode Island

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

United States,  Argentina,  Brazil,  Canada,  China,  Israel,  Japan,  Korea, Republic of,  Mexico,  New Zealand,  Peru,  Russian Federation,  Thailand,  Turkey, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-free survival (PFS)		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)
Primary	Objective response rate (ORR) as determined by an independent review facility (IRF)		Up to 2.5 years
Secondary	ORR as determined by the investigator		Up to 2.5 years
Secondary	Duration of response (DOR)		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)
Secondary	Overall survival (OS)		From randomization to death from any cause (up to 2.5 years)
Secondary	PFS		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)
Secondary	Complete response rate (CRR)		Up to 2.5 years
Secondary	Duration of complete response (DOCR)		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)
Secondary	Time to deterioration in physical functioning and fatigue as measured by the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30		Up to 2.5 years
Secondary	Time to deterioration in lymphoma symptoms as measured by the functional assessment of cancer therapy lymphoma subscale (FACT-Lym LymS)		Up to 2.5 years
Secondary	Incidence of adverse events (AEs)		Up to 2.5 years
Secondary	Change from baseline in peripheral neuropathy as measured by the functional assessment of cancer therapy/gynecologic oncology group - neurotoxicity (FACT/GOG-NTX)		Up to 2.5 years
Secondary	Serum concentration of mosunetuzumab		Up to 2.5 years
Secondary	Plasma concentration of polatuzumab vedotin		Up to 2.5 years
Secondary	Change from baseline in the EuroQol 5-dimension, 5-level questionnaire (EuroQol EQ 5D-5L) index-based scores		Up to 2.5 years
Secondary	Change from baseline in the EuroQol EQ 5D-5L visual analog scale (VAS) scores		Up to 2.5 years
Secondary	Incidence of anti-drug antibodies (ADAs) to mosunetuzumab		Up to 2.5 years
Secondary	Incidence of anti-drug antibodies (ADAs) to polatuzumab vedotin		Up to 2.5 years