An Open-Label, Phase I/II Study to Evaluate the Safety, Pharmacokinetics and Preliminary Anti-Tumor Activity of Englumafusp Alfa (RO7227166, A CD19 Targeted 4-1BB Ligand) in Combination With Obinutuzumab and in Combination With Glofitamab Following a Pre-treatment Dose of Obinutuzumab Administered in Participants 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? RO7227166 CD19-Targeted 4-1BB Ligand
Status: Recruiting
Location: See all (39) locations...
Intervention Type: Drug
Study Type: Interventional
Study Phase: Phase 1/Phase 2
SUMMARY

This is a phase I/II, open-label, dose-escalation study designed to evaluate the safety, tolerability, and efficacy of englumafusp alfa (RO7227166) in participants with relapsed/refractory Non-Hodgkin's Lymphoma (r/r NHL). Englumafusp alfa will be administered by intravenous (IV) infusion in combination with obinutuzumab and in combination with glofitamab. A fixed dose of obinutuzumab (Gpt; pre-treatment) will be administered up to seven days prior to the first administration of englumafusp alfa and seven days prior to the first administration of glofitamab. This entry-into-human study is divided into a dose-escalation stage (Part I and Part II) and a dose expansion stage (Part III).

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

• History or status of a histologically-confirmed hematological malignancy that is expected to express CD19 and CD20; relapse after or failure to respond to at least one prior treatment regimen; no available treatment options that are expected to prolong survival (Part I and II); relapsed after or failed to respond to only one prior systemic treatment regimen (Part III)

• Must have at least one measurable target lesion (\>/= 1.5 cm) in its largest dimension by computed tomography scan

• Able and willing to provide a fresh biopsy from a safely accessible site, per Investigator's determination, providing the participant has more than one measurable target lesion

• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, or \</= 2 for some participants in Part III

• Life expectancy of \>/= 12 weeks

• Adverse events from prior anti-cancer therapy must have resolved to Grade \</= 1

• Adequate liver, hematological, and renal function

• Negative test results for acute or chronic hepatitis B virus infection

• Negative test results for hepatitis C virus and HIV

• The contraception and abstinence requirements are intended to prevent exposure of an embryo to the study treatment. The reliability of sexual abstinence for male and/or female enrollment eligibility needs to be evaluated in relation to the duration of the clinical study and the preferred and usual lifestyle of the participant. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or post-ovulation methods) and withdrawal are not acceptable methods of preventing drug exposure

• Female participants: A female participant is eligible to participate if she is not pregnant and not breastfeeding, and if at least one of the following applies: women of non-childbearing potential (WONCBP); women of child bearing potential (WOCBP) who agree to remain abstinent or use two highly effective contraceptive methods with a failure rate of \<1% per year during the treatment period and for at least 18 months after obinutuzumab or 3.5 months after the last dose of englumafusp alfa, 2 months after last dose of glofitamab, or 3 months after the last dose of tocilizumab, whichever is longer. Examples of contraceptive methods with a failure rate of \< 1% per year include bilateral tubal occlusion/ ligation, male sexual partner who is sterilized, established proper use of hormonal contraceptives that inhibit ovulation, hormone-releasing intrauterine devices and copper intrauterine devices. Hormonal contraceptive methods must be supplemented by a barrier method; have a negative pregnancy test (blood) within the 7 days prior to the first study treatment administration

• Male participants: During the treatment period and for at least 3 months after obinutuzumab, or 3.5 months after the last dose of englumafusp alfa, 2 months after the last dose of glofitamab, or 2 months after the last dose of tocilizumab whichever is longer, agreement to: Remain abstinent or use contraceptive measures such as a condom plus an additional contraceptive method that together result in a failure rate of \< 1% per year, with a partner who is a women of childbearing potential. With pregnant female partner, remain abstinent or use contraceptive measures such as a condom to avoid exposing the embryo; refrain from donating sperm during this same period

Locations
United States
California
City of Hope Medical Center
ACTIVE_NOT_RECRUITING
Pasadena
University of California San Francisco
RECRUITING
San Francisco
Colorado
Colorado Blood Cancer Institute (CBCI) at Presbyterian/ St. Luke's Medical Center
RECRUITING
Denver
Massachusetts
Beth Israel Medical Center
RECRUITING
Boston
Missouri
Washington University School of Medicine
RECRUITING
St Louis
Ohio
OhioHealth Research Institute
RECRUITING
Columbus
Texas
The University of Texas MD Anderson Cancer Center
RECRUITING
Houston
Other Locations
Australia
Peter Maccallum Cancer Centre
RECRUITING
Melbourne
The Alfred Hospital
RECRUITING
Melbourne
Belgium
UZ Gent
RECRUITING
Ghent
Canada
Queen Elizabeth II Health Sciences Centre
RECRUITING
Halifax
Jewish General Hospital
RECRUITING
Montreal
China
Beijing Cancer Hospital
RECRUITING
Beijing
Shandong Cancer Hospital
RECRUITING
Jinan
Fudan University Shanghai Cancer Center
RECRUITING
Shanghai
The First Affiliated Hospital of Xiamen University
RECRUITING
Xiamen
Denmark
Aarhus Universitetshospital Skejby
RECRUITING
Aarhus N
Rigshospitalet
RECRUITING
København Ø
Odense Universitetshospital
RECRUITING
Odense C
France
CHRU de Lille
RECRUITING
Lille
CHU Montpellier - Saint ELOI
RECRUITING
Montpellier
Centre Hospitalier Lyon Sud
RECRUITING
Pierre-bénite
CHU DE RENNES - CHU Pontchaillou
RECRUITING
Rennes
Italy
Asst Papa Giovanni Xxiii
RECRUITING
Bergamo
Irccs Istituto Europeo Di Oncologia (IEO)
RECRUITING
Milan
Istituto Nazionale Tumori Irccs Fondazione g. Pascale
RECRUITING
Napoli
Istituto Clinico Humanitas
RECRUITING
Rozzano
New Zealand
Auckland City Hospital, Cancer and Blood Research
RECRUITING
Auckland
Waikato Hospital - Cancer and Blood Research Trials Unit
RECRUITING
Hamilton
Republic of Korea
Pusan National University Hospital
RECRUITING
Busan
Asan Medical Center
RECRUITING
Seoul
Samsung Medical Center
RECRUITING
Seoul
Seoul National University Hospital
RECRUITING
Seoul
Spain
Hospital Universitari Vall d'Hebron
RECRUITING
Barcelona
Hospital Duran i Reynals L'Hospitalet
RECRUITING
L'hospitalet De Llobregat
Hospital Univ. 12 de Octubre
RECRUITING
Madrid
Hospital Clinico Universitario Virgen de la Victoria
RECRUITING
Málaga
United Kingdom
The HOPE Clinical Trials Unit
RECRUITING
Leicester
University College London Hospitals NHS Foundation Trust
RECRUITING
London
Contact Information
Primary
Reference Study ID Number: BP41072 https://forpatients.roche.com/
global-roche-genentech-trials@gene.com
888-662-6728 (U.S. and Canada)
Time Frame
Start Date: 2019-08-13
Estimated Completion Date: 2027-03-31
Participants
Target number of participants: 498
Treatments
Experimental: Part I
Combination Dose-Escalation: Mixed r/r NHL participants will receive a fixed dose of obinutuzumab up to seven days prior to first administration of englumafusp alfa. Englumafusp alfa will be administered by intravenous (IV) infusion in combination with obinutuzumab in a three-weekly schedule (Q3W).
Experimental: Part II
Combination Dose-Escalation: Mixed r/r participants and participants with mixed r/r mantle cell lymphoma (MCL) and Richters transformation will receive a fixed dose of obinutuzumab seven days prior to first administration of englumafusp alfa. Englumafusp alfa will be administered by IV infusion in combination with glofitamab in a three-weekly schedule (Q3W).
Experimental: Part III
Dose-Expansion Stage: Participants with r/r diffuse large B-cell lymphoma not otherwise specified (DLBCL NOS), high-grade B-cell lymphoma (HGBCL), primary mediastinal B-cell lymphoma (PMBCL), and DLBCL arising from FL (transformed FL) will receive englumafusp alfa administered by IV infusion in combination with glofitamab in a three-weekly schedule (Q3W).
Related Therapeutic Areas
Sponsors
Leads: Hoffmann-La Roche

This content was sourced from clinicaltrials.gov

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