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Trial record 1 of 1 for:    NCT04077723
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A Study to Evaluate the Safety, Pharmacokinetics and Preliminary Anti-Tumor Activity of RO7227166 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

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ClinicalTrials.gov Identifier: NCT04077723
Recruitment Status : Recruiting
First Posted : September 4, 2019
Last Update Posted : July 27, 2020
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

Brief Summary:
This is a phase I, open-label, dose-escalation study designed to evaluate the safety, tolerability, and efficacy of RO7227166 in participants with relapsed/refractory Non-Hodgkin's Lymphoma (r/r NHL). RO7227166 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 seven days prior to the first administration of RO7227166 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).

Condition or disease Intervention/treatment Phase
Lymphoma, Non-Hodgkin Drug: RO7227166 Drug: Obinutuzumab Drug: Glofitamab Drug: Tocilizumab Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 207 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Open-Label, Phase I Study to Evaluate the Safety, Pharmacokinetics and Preliminary Antitumor Activity of 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
Actual Study Start Date : August 13, 2019
Estimated Primary Completion Date : January 3, 2023
Estimated Study Completion Date : January 3, 2023

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lymphoma

Arm Intervention/treatment
Experimental: Part I
Combination Dose-Escalation: Mixed r/r NHL participants will receive a fixed dose of obinutuzumab seven days prior to first administration of RO7227166. RO7227166 will be administered by intravenous (IV) infusion in combination with obinutuzumab in a three-weekly schedule (Q3W).
Drug: RO7227166
RO7227166 will be administered by intravenous (IV) infusion three-weekly (Q3W) in combination with a fixed dose of obinutuzumab (Part I) and in combination with a fixed dose of glofitamab (Part II and Part III).
Other Name: A CD19 Targeted 4-1BB Ligand

Drug: Obinutuzumab
A fixed dose of obinutuzumab will be administered seven days prior to first does of RO7227166 and glofitamab and then Q3W in combination with RO7227166 in Part I
Other Name: Gpt, RO5072759, Gazyva, Gazyvaro

Drug: Tocilizumab
Participants will receive IV tocilizumab as needed to treat cytokine release syndrome (CRS).
Other Name: Actemra, RoActemra

Experimental: Part II
Combination Dose-Escalation: Mixed r/r NHL participants will receive a fixed dose of obinutuzumab seven days prior to first administration of RO7227166. RO7227166 will be administered by IV infusion in combination with glofitamab in a three-weekly schedule (Q3W).
Drug: RO7227166
RO7227166 will be administered by intravenous (IV) infusion three-weekly (Q3W) in combination with a fixed dose of obinutuzumab (Part I) and in combination with a fixed dose of glofitamab (Part II and Part III).
Other Name: A CD19 Targeted 4-1BB Ligand

Drug: Obinutuzumab
A fixed dose of obinutuzumab will be administered seven days prior to first does of RO7227166 and glofitamab and then Q3W in combination with RO7227166 in Part I
Other Name: Gpt, RO5072759, Gazyva, Gazyvaro

Drug: Glofitamab
A fixed dose of glofitamab will be administered Q3W in combination with RO7227166 in Part II and Part III
Other Name: CD20-TCB, RO7082859

Drug: Tocilizumab
Participants will receive IV tocilizumab as needed to treat cytokine release syndrome (CRS).
Other Name: Actemra, RoActemra

Experimental: Part III
Dose-Expansion Stage: Participants with r/r follicular lymphoma (FL) and r/r diffuse large B-cell lymphoma (DLBCL) will receive RO7227166 administered by IV infusion in combination with glofitamab in a three-weekly schedule (Q3W).
Drug: RO7227166
RO7227166 will be administered by intravenous (IV) infusion three-weekly (Q3W) in combination with a fixed dose of obinutuzumab (Part I) and in combination with a fixed dose of glofitamab (Part II and Part III).
Other Name: A CD19 Targeted 4-1BB Ligand

Drug: Obinutuzumab
A fixed dose of obinutuzumab will be administered seven days prior to first does of RO7227166 and glofitamab and then Q3W in combination with RO7227166 in Part I
Other Name: Gpt, RO5072759, Gazyva, Gazyvaro

Drug: Glofitamab
A fixed dose of glofitamab will be administered Q3W in combination with RO7227166 in Part II and Part III
Other Name: CD20-TCB, RO7082859

Drug: Tocilizumab
Participants will receive IV tocilizumab as needed to treat cytokine release syndrome (CRS).
Other Name: Actemra, RoActemra




Primary Outcome Measures :
  1. Nature and frequency of dose-limiting toxicities (DLTs) [ Time Frame: 28 days in Part I and Part II ]
  2. Proportion of Participants with Adverse Event (AE) [ Time Frame: Part I: Up to 24 months; Part II/III: Up to 18 months ]
    Incidence, nature, and severity of AEs graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0

  3. Overall Response Rate (ORR) [ Time Frame: Part I: Up to 24 months; Part II/III: Up to 18 months ]
  4. Disease Control Rate (DCR) [ Time Frame: Part I: Up to 24 months; Part II/III: Up to 18 months ]
  5. Duration of Response (DOR) [ Time Frame: After end of Study approximately every 3 months until death, loss to follow-up or study termination ]
  6. Progression-free Survival (PFS) [ Time Frame: After end of Study approximately every 3 months until death, loss to follow-up or study termination ]
  7. Overall Survival (OS) [ Time Frame: After end of Study approximately every 3 months until death, loss to follow-up or study termination ]

Secondary Outcome Measures :
  1. Total exposure (area under the concentration time curve [AUC]) of RO7227166 in combination with obinutuzumab and glofitamab [ Time Frame: Part I: Up to 24 months; Part II: Up to 18 months ]
  2. Maximum serum concentration (peak concentration, Cmax) of RO7227166 in combination with obinutuzumab and glofitamab [ Time Frame: Part I: Up to 24 months; Part II: Up to 18 months ]
  3. Minimum serum concentration (trough concentration, Cmin) of RO7227166 in combination with obinutuzumab and glofitamab [ Time Frame: Part I: Up to 24 months; Part II: Up to 18 months ]
  4. Clearance (CL) of RO7227166 in combination with obinutuzumab and glofitamab [ Time Frame: Part I: Up to 24 months; Part II: Up to 18 months ]
  5. Volume of distribution of steady state (Vss) and half-life (t1/2) of RO7227166 in combination with obinutuzumab and glofitamab [ Time Frame: Part I: Up to 24 months; Part II: Up to 18 months ]
  6. ORR [ Time Frame: Part I: Up to 24 months; Part II/III Up to 18 months ]
  7. DCR [ Time Frame: Part I: Up to 24 months; Part II/III Up to 18 months ]
  8. DOR [ Time Frame: After end of Study approximately every 3 months until death, loss to follow-up or study termination ]
  9. PFS [ Time Frame: After end of Study approximately every 3 months until death, loss to follow-up or study termination ]
  10. OS [ Time Frame: After end of Study approximately every 3 months until death, loss to follow-up or study termination ]
  11. Proportion of Participants with Adverse Event (AE) [ Time Frame: After end of Study approximately every 3 months until death, loss to follow-up or study termination ]
    Incidence, nature, and severity of AEs graded according to the NCI CTCAE v5.0

  12. Total exposure (area under the concentration time curve [AUC]) of RO7227166 in combination with glofitamab [ Time Frame: Part III: Up to 18 months ]
  13. Maximum serum concentration (peak concentration, Cmax) of RO7227166 in combination with glofitamab [ Time Frame: Part III: Up to 18 months ]
  14. Minimum serum concentration (trough concentration, Cmin) of RO7227166 in combination with glofitamab [ Time Frame: Part III: Up to 18 months ]
  15. Clearance (CL) of RO7227166 in combination with glofitamab [ Time Frame: Part III: Up to 18 months ]
  16. Volume of distribution of steady state (Vss) and half-life (t1/2) of RO7227166 in combination with glofitamab Part I/II/III [ Time Frame: Part III: Up to 18 months ]
  17. T-cell and Natural killer (NK)-cell status in blood, using markers of T and NK-cell lineage, function and activation including, but not limited to, CD3, CD8, 41BB, and Ki67 expression [ Time Frame: Part I: Up to 24 months; Part II/III: Up to 18 months ]
  18. B-cell reduction in blood and tumor tissue [ Time Frame: Part I: Up to 24 months; Part II/III: Up to 18 months ]
  19. Change from Baseline in RO7227166 Anti-Drug Antibody (ADA) Titer [ Time Frame: Part 1: Up to 24 months; Part ll/lll: Up to 18 months ]
  20. Time to First Complete Response (TFCR) [ Time Frame: Up to 18 months ]
  21. Time to First Overall Response (TFOR) [ Time Frame: Up to 18 months ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Depending upon study part: a 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; and no available treatment options that are expected to prolong survival
  • Must have at least one measureable 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 performance status of 0 or 1
  • Life expectancy of >/= 12 weeks
  • Adverse events from prior anti-cancer therapy must have resolved to Grade </= 1
  • Adequate liver, haematological, 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 RO7227166, 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 2 months after the last dose of RO7227166, glofitamab, or 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

Exclusion Criteria:

  • Circulating lymphoma cells, defined by out of range (high) absolute lymphocyte count or the presence of abnormal cells in the peripheral blood differential signifying circulating lymphoma cells
  • Participants with acute bacterial, viral, or fungal infection at baseline, confirmed by a positive blood culture within 72 hours prior to obinutuzumab infusion or by clinical judgment in the absence of a positive blood culture
  • Participants with known active infection, or reactivation of a latent infection, whether bacterial, viral fungal, mycobacterial, or other pathogens (excluding fungal infections of nail beds) or any major episode of infection requiring hospitalization or treatment with IV antibiotics
  • Pregnant or breast-feeding or intending to become pregnant during the study
  • Prior treatment with systemic immunotherapeutic agents, including, but not limited to, radio-immunoconjugates, antibody-drug conjugates, immune/cytokines or monoclonal antibodies within 4 weeks or five half-lives of the drug, whichever is longer, before obinutuzumab infusion on D-7
  • History of treatment-emergent immune-related AEs associated with prior immunotherapeutic agents and auto-immune disease
  • Treatment with standard radiotherapy, any chemotherapeutic agent, or treatment with any other investigational or approved anti-cancer agent within 4 weeks or 5 half-lives of the drug, whichever is longer, prior to obinutuzumab infusion
  • Prior solid organ transplantation
  • Prior allogeneic stem cell transplant (SCT) and prior chimeric antigen receptor -T-cell therapy
  • Autologous SCT within 100 days prior to obinutuzumab infusion
  • History of severe allergic or anaphylactic reactions to monoclonal antibody therapy and confirmed progressive multifocal leukoencephalopathy
  • Current or past history of central nervous system (CNS) lymphoma and CNS disease
  • Evidence of significant, uncontrolled concomitant diseases that could affect compliance with the protocol or interpretation of results, including diabetes mellitus, history of relevant pulmonary disorders and known autoimmune diseases
  • Major surgery or significant traumatic injury < 28 days prior to the Gpt infusion or anticipation of the need for major surgery during study treatment
  • Participants with another invasive malignancy in the last 2 years
  • Significant cardiovascular disease
  • Administration of a live, attenuated vaccine within 4 weeks before Gpt infusion or anticipation that such a live attenuated vaccine will be required during the study
  • Received systemic immunosuppressive medications (including but not limited to cyclohosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor agents) with the exception of corticosteroid treatment <=25 mg/day of prednisone or equivalent, however there must be documentation that the participant was on a stable dose of at least a 2-week duration prior to Gpt infusion. Inhaled and topical steriods are permitted

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04077723


Contacts
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Contact: Reference Study ID Number: BP41072 www.roche.com/about_roche/roche_worldwide.htm 888-662-6728 (U.S. and Canada) global-roche-genentech-trials@gene.com

Locations
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Australia, Victoria
Peter Maccallum Cancer Centre Recruiting
Melbourne, Victoria, Australia, 3000
Belgium
UZ Gent Recruiting
Gent, Belgium, 9000
Denmark
Rigshospitalet; Hæmatologisk Klinik Recruiting
København Ø, Denmark, 2100
France
CHRU de Lille Recruiting
Lille, France, 59037
CHU Montpellier - Saint ELOI Not yet recruiting
Montpellier, France, 34295
Centre Hospitalier Lyon Sud Not yet recruiting
Pierre Benite, France, 69495
CHU DE RENNES - CHU Pontchaillou; Service d'Hématologie Clinique Adulte Not yet recruiting
Rennes, France, 35033
Italy
ASST PAPA GIOVANNI XXIII; Ematologia Recruiting
Bergamo, Lombardia, Italy, 24127
Istituto Clinico Humanitas;U.O. Oncologia Medica Ed Ematologia Recruiting
Rozzano, Lombardia, Italy, 20089
Spain
Hospital Universitari Vall d'Hebron; Servicio de Hematologia Recruiting
Barcelona, Spain, 08035
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
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Study Director: Clinical Trials Hoffmann-La Roche
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Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT04077723    
Other Study ID Numbers: BP41072
2019-000416-28 ( EudraCT Number )
First Posted: September 4, 2019    Key Record Dates
Last Update Posted: July 27, 2020
Last Verified: July 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here (https://vivli.org/members/ourmembers/). For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm).

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Lymphoma
Lymphoma, Non-Hodgkin
Lymphoma, B-Cell
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Obinutuzumab
Antineoplastic Agents, Immunological
Antineoplastic Agents