Phase
Condition
Lymphoma, B-cell
Lymphoma
Treatment
Mosunetuzumab
Glofitamab
Polatuzumab Vedotin
Clinical Study ID
Ages > 18 All Genders
Study Summary
Eligibility Criteria
Inclusion
Inclusion Criteria:
Male or female participant aged 18 years or older
Pathologic diagnosis of relapsed (disease that has recurred following a response) orrefractory (disease that failed to respond to prior therapy) B-NHL (2016 WorldHealth Organization classification) who have failed, or been intolerant to anyapproved therapy and had received at least two systemic treatment regimens indose-escalation part; and at least one systemic treatment regimen in dose-expansionpart
Aggressive B Cell Lymphomas:
DLBCL (including transformed diseases, but for Arms E and F, includingtransformed FL only)
HGBCL
FL Grade 3b
Indolent NHL:
FL (Grade 1-3a)
MZL
For Arm C only:
MCL
BL
Life expectancy of at least 24 weeks according to Investigator's judgement
Need of systemic treatment for any of the listed indications as assessed by theinvestigator, including indolent B-NHLs (e.g. FL and MZL)
Measurable disease as defined by the 2014 Lugano Classification
Availability of formalin-fixed paraffin-embedded tumor tissue block
ECOG performance status 0 to 2
Adequate organ function
Women of childbearing potential (WOCBP) must agree to use a highly effective methodof contraception from the time of giving informed consent until at least 10 monthsafter the last dose of loncastuximab tesirine. Men with female partners who are ofchildbearing potential must agree to use a condom when sexually active or practicetotal abstinence from the time of giving informed consent the first dose until atleast 7 months after the last dose of loncastuximab tesirine. Men must refrain fromdonating sperm during this same period. For the arm that includes glofitamab, WOCBPmust agree to use contraceptive methods that result in a failure of less than 1% peryear or remain abstinent (refrain from heterosexual intercourse) during thetreatment period and for at least 18 months after pretreatment with obinutuzumab.For the arm that includes mosunetuzumab, WOCBP must agree to use contraceptivemethods that result in a failure of less than 1% per year or remain abstinent (refrain from heterosexual intercourse) during the treatment period and for at least 3 months after the final dose of mosunetuzumab and tocilizumab (if applicable).
Exclusion
Exclusion Criteria:
Known history of hypersensitivity resulting in treatment discontinuation to orpositive serum human ADA to a CD19 antibody
Previous therapy with loncastuximab tesirine
Previous treatment with polatuzumab vedotin, glofitamab or mosunetuzumab (applied torelevant arm and/or cohort of the specific drug administered)
Participants who received previous treatment of polatuzumab vedotin containingregimen will be excluded from Arm C
Participants who received previous treatment of glofitamab containing regimenwill be excluded from Arm E
Participants who received previous treatment of mosunetuzumab containingregimen will be excluded from Arm F
Allogenic or autologous stem cell transplant within 60 days prior to start of studydrug (C1 D1)
Human immunodeficiency virus (HIV) seropositive
Serologic evidence of chronic hepatitis B virus (HBV) infection and unable orunwilling to receive standard prophylactic antiviral therapy or with detectable HBVviral load
Serologic evidence of hepatitis C virus (HCV) infection without completion ofcurative treatment or with detectable HCV viral load
History of confirmed progressive multifocal leukoencephalopathy
History of Stevens-Johnson syndrome, toxic epidermal necrolysis, or macrophageactivation syndrome (MAS)/hemophagocytic lymphohistiocytosis (HLH)
Lymphoma with active central nervous system (CNS) involvement at the time ofscreening, including leptomeningeal disease
Clinically significant third space fluid accumulation (i.e., ascites requiringdrainage or pleural effusion that is either requiring drainage or associated withshortness of breath)
Breastfeeding or pregnant
Significant medical comorbidities
Major surgery, radiotherapy, chemotherapy, or other anti-neoplastic therapy, within 14 days prior to start of study drugs (C1 D1), except shorter if approved by theSponsor
Live vaccine within 4 weeks prior to C1D1
Failure to recover to Grade ≤1 (Common Terminology Criteria for Adverse Events [CTCAE] version 5.0) from acute non-hematologic toxicity (Grade ≤2 alopecia) due toprevious therapy prior to screening
Active second primary malignancy other than non-melanoma skin cancers,non-metastatic prostate cancer, in situ cervical cancer, ductal or lobular carcinomain situ of the breast, or other malignancy that the Sponsor's medical monitor andInvestigator agree and document should not be exclusionary
Extra Exclusion Criteria for Arms E (includes glofitamab) and F (includes mosunetuzumab) Note: as applicable, the arm-specific exclusion criteria may supersede the general ones, such as stem cell transplant.
Prior allogeneic stem cell transplant and solid organ transplant
Autologous stem cell transplant within 100 days prior to C1D1
History of CNS lymphoma or leptomeningeal infiltration
Current or history of CNS disease, such as stroke, epilepsy, CNS vasculitis, orneurodegenerative disease
Known active infection, reactivation of a latent infection, whether bacterial,viral, fungal, mycobacterial, or other pathogens (excluding fungal infections ofnail beds), or any major episode of infection requiring hospitalization or treatmentwith intravenous (IV) antibiotics within four weeks prior to C1D1
Active or history of autoimmune disease or immune deficiency, motor neuropathyconsidered of autoimmune origin and other central nervous system (CNS) autoimmunediseases, including but not limited to, myasthenia gravis, myositis, autoimmunehepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory boweldisease, antiphospholipid antibody syndrome, Wegener granulomatosis, Sjögrensyndrome, Guillain-Barré syndrome, or multiple sclerosis, with, with certainexceptions
Prior treatment with anti-cancer/lymphoma targeted therapies (e.g., tyrosine kinaseinhibitors, systemic immunotherapeutic/immunostimulating agents, including, but notlimited to, cluster of differentiation 137 agonists or immune checkpoint blockadetherapies, including anti-cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4),anti-programmed cell death protein 1 (PD1), and anti-programmed death ligand 1 (PDL1) therapeutic antibodies, radio-immunoconjugates, ADCs, immune/cytokines andmonoclonal antibodies) or treatment with systemic immunosuppressive medication (including, but not limited to, cyclophosphamide, azathioprine, methotrexate,thalidomide, and anti-tumor necrosis factor agents) within 4 weeks or fivehalf-lives of the drug, whichever is shorter, prior to C1D1, or anticipation of needfor systemic immunosuppressive medication during study treatment, with certainexceptions
Prior treatment with CAR-T-cell therapy within 100 days prior to C1D1; primaryrefractory patients (progressive or persistent disease within 30 days) to CAR-T-celltherapy are not eligible.
Toxicities from prior anti-cancer therapy including immunotherapy that did notresolve to ≤ Grade 1 with the exception of alopecia, endocrinopathy managed withreplacement therapy and stable vitiligo
Any history of immune-related Grade ≥3 AE with the exception of endocrinopathymanaged with replacement therapy
Ongoing corticosteroid use greater than 25 mg/day of prednisone or equivalent within 4 weeks prior and during study treatment
Administration of a live attenuated vaccine within 4 weeks prior to the first doseof study treatment or anticipation that such a live attenuated vaccine will berequired during the study or within 5 months after last dose of study treatment
Extra Exclusion Criteria for Arm E (includes glofitamab) only.
• Known history of hypersensitivity to obinutuzumab
Study Design
Study Description
Connect with a study center
Universitair Ziekenhuis Gent
Gent, 9000
BelgiumActive - Recruiting
Centre Hospitalier Universitaire Universite Catholique de Louvain - Site Godinne
Yvoir, B-5530
BelgiumActive - Recruiting
Fakultni Nemocnice Brno
Brno, South Moravian 625 00
CzechiaActive - Recruiting
Fakultni nemocnice Ostrava
Ostrava, 708 52
CzechiaActive - Recruiting
Fakultni nemocnice v Motole
Prague, 150 06
CzechiaActive - Recruiting
Fakultní Nemocnice Královské Vinohrady
Prague, 100 34
CzechiaActive - Recruiting
Azienda Socio Sanitaria Territoriale (ASST) Papa Giovanni XXIII
Bergamo, 24127
ItalyActive - Recruiting
Centro di Ricerche Cliniche - IRCCS Azienda Ospedaliero Universitaria di Bologna
Bologna, 40138
ItalyActive - Recruiting
Azienda Socio Sanitaria Territoriale (ASST) degli Spedali Civili di Brescia
Brescia, 25123
ItalyActive - Recruiting
Istituto Europeo di Oncologia
Milano, 20141
ItalyActive - Recruiting
Institut Català d'Oncologia - Hospital Duran i Reynals (ICO L'Hospitalet)
Barcelona, 08908
SpainActive - Recruiting
Hospital General Universitario Gregorio Marañón
Madrid, 28007
SpainActive - Recruiting
Hospital Universitario Ramón y Cajal
Madrid, 28034
SpainActive - Recruiting
Complejo Asistencial Universitario de Salamanca - Hospital Clínico
Salamanca, 37007
SpainActive - Recruiting
Hospital Universitari i Politècnic La Fe
Valencia, 46026
SpainActive - Recruiting
University College London Hospitals NHS Foundation Trust
London, NW1 2PG
United KingdomCompleted
Oxford University Hospitals NHS Foundation Trust
Oxford, OX3 7LE
United KingdomCompleted
University of California San Francisco - Fresno Center for Medical Education and Research
Clovis, California 93611
United StatesActive - Recruiting
Scripps Health - Prebys Cancer Center
San Diego, California 92103
United StatesActive - Recruiting
Miami Cancer Institute
Miami, Florida 33176
United StatesActive - Recruiting
Sylvester Comprehensive Cancer Center
Miami, Florida 33136
United StatesActive - Recruiting
Memorial Cancer Institute - Memorial Hospital West
Pembroke Pines, Florida 33028
United StatesActive - Recruiting
The Blood and Marrow Transplant Group of Georgia
Atlanta, Georgia 30342
United StatesActive - Recruiting
Winship Cancer Institute of Emory University
Atlanta, Georgia 30322
United StatesActive - Recruiting
Mission Cancer + Blood - Mission Cancer Foundation
Des Moines, Iowa 50309
United StatesActive - Recruiting
Beth Israel Deaconess Medical Center
Boston, Massachusetts 02215
United StatesActive - Recruiting
Dana-Farber Cancer Institute
Boston, Massachusetts 02215
United StatesActive - Recruiting
University of Minnesota
Minneapolis, Minnesota 55455
United StatesActive - Recruiting
Columbia University Irving Medical Center
New York, New York 10027
United StatesActive - Recruiting
Cleveland Clinic Main Campus
Cleveland, Ohio 44195
United StatesActive - Recruiting
Oregon Health and Science University
Portland, Oregon 97239
United StatesActive - Recruiting
Penn Medicine - Perelman Center for Advanced Medicine
Philadelphia, Pennsylvania 19104
United StatesActive - Recruiting
Allegheny Health Network - West Penn Hospital
Pittsburgh, Pennsylvania 15224
United StatesActive - Recruiting
Brown University Health - Rhode Island Hospital
Providence, Rhode Island 02903
United StatesActive - Recruiting
Hollings Cancer Center
Charleston, South Carolina 29425
United StatesSite Not Available
Avera Cancer Institute
Sioux Falls, South Dakota 57105
United StatesSite Not Available
Greco-Hainsworth Tennessee Oncology Centers for Research (GHCR)
Nashville, Tennessee 37203
United StatesActive - Recruiting
Baylor University Medical Center
Dallas, Texas 75246
United StatesActive - Recruiting
Huntsman Cancer Institute
Salt Lake City, Utah 84112
United StatesActive - Recruiting
Emily Couric Clinical Cancer Center
Charlottesville, Virginia 22903
United StatesActive - Recruiting
NEXT Virginia (Virginia Cancer Specialists)
Fairfax, Virginia 22031
United StatesSite Not Available
Froedtert & Medical College of Wisconsin
Milwaukee, Wisconsin 53226
United StatesActive - Recruiting
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