A Multicenter, Open-label, Phase I/II Study to Evaluate the Safety, Efficacy, Tolerability and Pharmacokinetics of Escalating Doses of Glofitamab (RO7082859) as a Single Agent and in Combination With Obinutuzumab Administered After a Fixed, Single Dose Pre-treatment of Obinutuzumab (Gazyva®/Gazyvaro™) in Patients With Relapsed/Refractory B-cell Non-hodgkin's Lymphoma

Who is this study for? Adult patients with Non-Hodgkin's Lymphoma
What treatments are being studied? Glofitamab
Status: Recruiting
Location: See all (37) locations...
Intervention Type: Drug
Study Type: Interventional
Study Phase: Phase 1/Phase 2
SUMMARY

This is a Phase I/II, multicenter, open-label, dose-escalation study designed to evaluate the efficacy, safety, tolerability and pharmacokinetics (PK) of a novel T-Cell bispecific (TCB), glofitamab, administered by intravenous (IV) infusion as a single agent and in combination with obinutuzumab, following pre-treatment with a one-time, fixed dose of obinutuzumab. This entry-into-human (EIH) study is divided in 3 parts: dose escalation (Parts I and II) and dose expansion (Part III). Single-participant dose-escalation cohorts will be used in Part I, followed by conversion to multiple participant dose-escalation cohorts (Part II), in order to define a tentative maximum tolerated dose (MTD) or optimal biological dose (OBD). The expansion cohorts (Part III) will be initiated when the tentative MTD/OBD is defined, to further evaluate the safety, PK and therapeutic activity of glofitamab.

Eligibility
Participation Requirements
Sex: All
Minimum Age: 18
Healthy Volunteers: f
View:

• Depending upon study part, a history or status of: 1) a histologically-confirmed hematological malignancy that is expected to express cluster of differentiation (CD)20; 2) relapse after or failure to respond to at least one prior treatment regimen; and 3) no available treatment options that are expected to prolong survival (e.g., standard chemotherapy or autologous stem cell transplant \[ASCT\])

• Measurable disease, defined as at least one bi-dimensionally measurable nodal lesion, defined as \> 1.5 cm in its longest dimension, or at least one bi-dimensionally measurable extranodal lesion, defined as \> 1.0 cm in its longest dimension

• Able to provide a tumor tissue pretreatment biopsy at last relapse or during screening from a safely accessible site, per investigator determination, providing the patient has more than one measurable target lesion

• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

• Life expectancy of \>/=12 weeks

• AEs from prior anti-cancer therapy must have resolved to Grade less than or equal to (\</=) 1

• Adequate liver, hematological and renal function

• Negative serologic or polymerase chain reaction (PCR) test results for acute or chronic Hepatitis B virus (HBV) infection

• Negative test results for Hepatitis C virus (HCV) and human immunodeficiency virus (HIV)

• Negative serum pregnancy test within 7 days prior to study treatment in women of childbearing potential. Women who are not of childbearing potential who are considered to be post-menopausal (at least 12 months of non-therapy amenorrhea) or surgically sterile (absence of ovaries and/or uterus) are not required to have a pregnancy test

Locations
United States
Illinois
Ingalls Memorial Hospital
WITHDRAWN
Harvey
Michigan
University of Michigan
ACTIVE_NOT_RECRUITING
Ann Arbor
Missouri
Washington University
RECRUITING
St Louis
New York
Mount Sinai Medical Center
ACTIVE_NOT_RECRUITING
New York
MSKCC
COMPLETED
New York
Pennsylvania
Allegheny Health Network (Pittsburg PA)
ACTIVE_NOT_RECRUITING
Pittsburgh
Utah
Hunstman Cancer Institute
WITHDRAWN
Salt Lake City
Washington
Swedish Cancer Inst.
ACTIVE_NOT_RECRUITING
Seattle
Other Locations
Australia
Peter Maccallum Cancer Centre
RECRUITING
Melbourne
Prince of Wales Hospital
ACTIVE_NOT_RECRUITING
Randwick
Belgium
Cliniques Universitaires St-Luc
RECRUITING
Brussels
UZ Gent
RECRUITING
Ghent
Canada
Princess Margaret Cancer Center
ACTIVE_NOT_RECRUITING
Toronto
Denmark
Rigshospitalet
RECRUITING
København Ø
Finland
Helsinki University Central Hospital
RECRUITING
Helsinki
France
Hopital Henri Mondor
RECRUITING
Créteil
Hopital Claude Huriez
RECRUITING
Lille
CHU Saint Eloi
RECRUITING
Montpellier
Ch Lyon Sud
RECRUITING
Pierre-bénite
CHU DE RENNES - CHU Pontchaillou
RECRUITING
Rennes
Italy
Fond. IRCCS Istituto Nazionale Tumori
RECRUITING
Milan
AUSL della Romagna
RECRUITING
Ravenna
Istituto Clinico Humanitas
ACTIVE_NOT_RECRUITING
Rozzano
A.O.U. Citta' Della Salute E Della Scienza-P.O. Molinette
WITHDRAWN
Turin
New Zealand
Auckland Cancer Trial Centre
ACTIVE_NOT_RECRUITING
Auckland
Poland
Uniwersyteckie Centrum Kliniczne
ACTIVE_NOT_RECRUITING
Gda?sk
Uniwersytecki Szpital Kliniczny w Poznaniu
RECRUITING
Późna
Centrum Onkologii-Instytut im. M. Sklodowskiej-Curie
WITHDRAWN
Warsaw
Uniwersytecki Szpital Kliniczny im. Jana Mikulicza-Radeckiego we Wroclawiu
ACTIVE_NOT_RECRUITING
Wroc?aw
Spain
Hospital Universitari Germans Trias i Pujol
ACTIVE_NOT_RECRUITING
Badalona
Hospital del Mar
ACTIVE_NOT_RECRUITING
Barcelona
Hospital Universitari Vall d'Hebron
RECRUITING
Barcelona
Hospital Duran i Reynals L'Hospitalet
ACTIVE_NOT_RECRUITING
L'hospitalet De Llobregat
Hospital Univ. 12 de Octubre
ACTIVE_NOT_RECRUITING
Madrid
Hospital Universitario Marques de Valdecilla
ACTIVE_NOT_RECRUITING
Santander
Taiwan
China Medical University Hospital
RECRUITING
Taichung
National Taiwan Universtiy Hospital
ACTIVE_NOT_RECRUITING
Taipei
Contact Information
Primary
Reference Study ID Number: NP30179 https://forpatients.roche.com/
global-roche-genentech-trials@gene.com
888-662-6728 (U.S. and Canada)
Time Frame
Start Date: 2017-02-21
Estimated Completion Date: 2029-12-31
Participants
Target number of participants: 920
Treatments
Experimental: Part I: Dose Escalation
Participants (single participant cohorts) will receive obinutuzumab pretreatment (Gpt) 1000 milligrams (mg) single dose IV infusion on Day -7 followed by glofitamab IV infusion on Day 1 and Day 8 of Cycle 1. From Cycle 2 onwards, ascending doses of glofitamab will be administered on Day 1 of every 2 week (Q2W) cycle up to Cycle 12 (24 weeks) or until unacceptable toxicity or disease progression. Glofitamab dosing will be initiated at 5 micrograms (mcg) (flat dose) followed by doses of 15 mcg, 45 mcg, 135 mcg, 405 mcg and 810 mcg.
Experimental: Part II: Dose Escalation
In each treatment regimen, participants will receive Gpt 1000 mg IV infusion on Day -7; or 2000 mg either administered on Day -7, or split into two 1000 mg doses on Days -1 and -7. The first glofitamab IV infusion will be given on Day 1 of Cycle 1 and a total of 12 cycles will be administered.~Monotherapy, glofitamab as a single agent: ascending doses of glofitamab administered on Day 1 of Q2W or every 3 week (Q3W) cycle until either the MTD/OBD is defined.~Combination Therapy: From Cycle 2 onwards, a fixed dose of 1000 mg obinutuzumab will be administered via IV infusion in combination with ascending doses of glofitamab on Day 1 of Q3W cycle until either the MTD/OBD is defined.~Step-up dosing: Q3W, participants will receive an initial low dose of glofitamab on Cycle 1 Day 1, followed by a higher dose on Cycle 1 Day 8; the total dose in Cycle 1 will not exceed the previously determined MTD. Higher doses may be explored from Cycle 2 or later cycles.
Experimental: Part III: Dose Expansion
Part III will start once MTD/OBD is defined. Participants will receive Gpt 1000 mg single dose IV infusion on Day -7, followed by glofitamab at a fixed dose regimen or step-up dose regimen on a Q2W or Q3W dosing schedule as determined in Part II. A total of 12 cycles will be administered.~Combination Therapy: From Cycle 2 onwards, a fixed dose of 1000 mg obinutuzumab will be administered via IV infusion in combination with glofitamab at the dosing regimen determined in Part II.
Related Therapeutic Areas
Sponsors
Leads: Hoffmann-La Roche

This content was sourced from clinicaltrials.gov

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