Try the modernized ClinicalTrials.gov beta website. Learn more about the modernization effort.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of RO7443904 in Combination With Glofitamab in Participants With Relapsed/Refractory B-Cell Non-Hodgkin's Lymphoma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05219513
Recruitment Status : Recruiting
First Posted : February 2, 2022
Last Update Posted : July 25, 2022
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

Brief Summary:
This is a first-in human, open-label, Phase 1 dose-escalation study in order to determine the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D) for intravenous (IV) and/or subcutaneous (SC) dosing schemes of this combination treatment, and to evaluate the safety, tolerability, pharmacokinetics, and preliminary anti-tumor activity of this combination treatment in participants with relapsed/refractory B-cell non Hodgkin lymphoma (r/r NHL).

Condition or disease Intervention/treatment Phase
Lymphoma, Non-Hodgkin Drug: RO7443904 Drug: Glofitamab Drug: Obinutuzumab Drug: Tocilizumab Phase 1

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 200 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Open-Label, Phase 1 Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of RO7443904 in Combination With Glofitamab in Participants With Relapsed/Refractory B-Cell Non-Hodgkin's Lymphoma
Actual Study Start Date : February 18, 2022
Estimated Primary Completion Date : April 1, 2024
Estimated Study Completion Date : April 1, 2024

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lymphoma

Arm Intervention/treatment
Experimental: Parts I-III: Dose-escalation of RO7443904
The dose-escalation of RO7443904 and glofitamab will take place every three weeks (Q3W) with obinutuzumab pre-treatment.
Drug: RO7443904
RO7443904 will be administered by subcutaneous (SC) or IV infusion on Cycle 2, Day 8. From Cycle 3 onward, RO7443904 will be given every 3 weeks (Q3W), for up to 12 cycles (Cycle = 21 days).

Drug: Glofitamab
Glofitamab will be administered through IV infusion starting with step-up dosing (2.5 mg/10 mg/30 mg) on C1D1, C1D8, and C2D1. Starting in Cycle 3, glofitamab will be given in 30 mg doses every three weeks (Q3W) with RO7443904, for up to 12 cycles (Cycle = 21 days).
Other Name: RO7082859

Drug: Obinutuzumab
Obinutuzumab will be administered once through IV infusion, at a 1 g dose in Cycle 1, on either Day -7, -4, or -3 (C1D-7, C1D-4, C1D-3).

Drug: Tocilizumab
Tocilizumab will be administered as necessary to treat cytokine release syndrome (CRS).
Other Name: Actemra

Experimental: Part IV: Dose-expansion of RO7443904
Part IV of this study will evaluate selected dose levels of RO7443904 in combination with glofitamab from Parts I-III in a Q3W regimen with obinutuzumab pre-treatment.
Drug: RO7443904
RO7443904 will be administered by subcutaneous (SC) or IV infusion on Cycle 2, Day 8. From Cycle 3 onward, RO7443904 will be given every 3 weeks (Q3W), for up to 12 cycles (Cycle = 21 days).

Drug: Glofitamab
Glofitamab will be administered through IV infusion starting with step-up dosing (2.5 mg/10 mg/30 mg) on C1D1, C1D8, and C2D1. Starting in Cycle 3, glofitamab will be given in 30 mg doses every three weeks (Q3W) with RO7443904, for up to 12 cycles (Cycle = 21 days).
Other Name: RO7082859

Drug: Tocilizumab
Tocilizumab will be administered as necessary to treat cytokine release syndrome (CRS).
Other Name: Actemra




Primary Outcome Measures :
  1. Nature and frequency of dose-limiting toxicities (DLTs) [ Time Frame: From 3 weeks (21 days) from the first administration of RO7443904 (Cycle 2 Day 8) to 1 week after the second administration of RO7443904 (Cycle 3 Day 8) ]
  2. Incidence, nature, and severity of AEs [ Time Frame: Up to 4 weeks after the last study treatment dose ]
    graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0 and for cytokine-release syndrome (CRS) and neurotoxicity (immune effector cell-associated neurotoxicity syndrome; ICANS) according to the American Society for Transplantation and Cellular Therapy (ASTCT) consensus grading


Secondary Outcome Measures :
  1. Maximum concentration (Cmax) of RO7443904 [ Time Frame: Up to 9 months ]
  2. Area under the curve (AUC) of RO7443904 [ Time Frame: Up to 9 months ]
  3. Clearance (CL) of RO7443904 [ Time Frame: Up to 9 months ]
  4. Volume of distribution (Vd) of RO7443904 [ Time Frame: Up to 9 months ]
  5. Half-life (t1/2) of RO7443904 [ Time Frame: Up to 9 months ]
  6. Percentage of Participants with RO7443904 anti-drug antibodies (ADAs) during the study relative to the prevalence of ADA at baseline [ Time Frame: Up to 9 months ]
  7. Time to maximum concentration (Tmax) of RO7443904 [ Time Frame: Up to 9 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.


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

Inclusion Criteria:

  • Body weight >=40 kg
  • Histologically confirmed hematological malignancy that is expected to express CD19 and CD20 and with clinical evidence of treatment need; 2) relapse after or failure to respond to at least two prior treatment regimens; and 3) no other available treatment options that are known to provide clinical benefit
  • Must have at least one measurable target lesion (>=1.5 cm) in its largest dimension by computed tomography (CT) scan
  • Able and willing to provide a fresh tumor biopsy from a safely accessible site, per Investigator's determination
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
  • Life expectancy of >=12 weeks
  • 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 HIV
  • A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies: 1) Women of non-childbearing potential 2) Women of childbearing potential (WOCBP), who, agree to remain abstinent (refrain from heterosexual intercourse) or use of one highly effective contraceptive method during the treatment period and for at least 18 months after obinutuzumab or 5 months after the final dose of RO7443904, 2 months after final dose of glofitamab or 3 months after the final dose of tocilizumab
  • Male participants must remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures such as a condom plus an additional contraceptive method with a partner who is a WOCBP during the treatment period and for at least 3 months after obinutuzumab, 5 months after the final dose of RO7443904, 2 months after the final dose of glofitamab or 2 months after the final dose of tocilizumab, whichever is longer

Exclusion Criteria:

  • Circulating lymphoma cells, defined by out-of-range (high) absolute lymphocyte count (ALC) or the presence of abnormal cells in the peripheral blood signifying circulating lymphoma cells
  • Participants with acute bacterial, viral, or fungal infection at screening
  • Participants with known active infection or reactivation of a latent infection
  • Pregnant, breastfeeding, or intending to become pregnant during the study
  • Prior treatment with systemic immunotherapeutic agents
  • History of treatment-emergent, immune-related adverse events (AEs) associated with prior immunotherapeutic agents
  • No persistent AEs from prior anti-cancer therapy Grade >=1
  • Treatment with standard radiotherapy, any chemotherapeutic agent, or treatment with any other investigational or approved anti-cancer agent
  • Prior solid organ transplantation
  • Prior allogeneic stem cell transplant (SCT)
  • Autologous SCT within 100 days prior to obinutuzumab infusion
  • Autoimmune disease in active phase or exacerbation/flare within at least 6 months of enrollment
  • History of immune deficiency disease that increases the risk of infection
  • History of severe allergic or anaphylactic reactions to monoclonal antibody therapy
  • History of confirmed progressive multifocal leukoencephalopathy
  • Current or past history of central nervous system (CNS) lymphoma or CNS disease
  • Evidence of significant, uncontrolled concomitant diseases that could affect compliance with the protocol or interpretation of results
  • 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
  • History of illicit drug or alcohol abuse within 12 months prior to screening, in the Investigator's judgment
  • Any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that would contraindicate the use of an investigational drug

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): NCT05219513


Contacts
Layout table for location contacts
Contact: Reference Study ID Number: BP43131 https://forpatients.roche.com/ 888-662-6728 (U.S. and Canada) global-roche-genentech-trials@gene.com

Locations
Layout table for location information
Australia, Victoria
Peter MacCallum Cancer Centre; Department of Haematology Recruiting
Melbourne, Victoria, Australia, 3002
Denmark
Rigshospitalet; Hæmatologisk Klinik, Klinisk Afprøvnings Team KAT Recruiting
København Ø, Denmark, 2100
France
CHRU Lille - Hôpital Claude Huriez; Service des Maladies du Sang Recruiting
Lille, France, 59037
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
United Kingdom
Leicester Royal Infirmary; Dept of Haematology Recruiting
Leicester, United Kingdom, LE1 5WW
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
Layout table for investigator information
Study Director: Clinical Trials Hoffmann-La Roche
Layout table for additonal information
Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT05219513    
Other Study ID Numbers: BP43131
First Posted: February 2, 2022    Key Record Dates
Last Update Posted: July 25, 2022
Last Verified: July 2022
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.clinicalstudydatarequest.com). Further details on Roche's criteria for eligible studies are available here (https://clinicalstudydatarequest.com/Study-Sponsors/Study-Sponsors-Roche.aspx). For further details on Roche's Global Policy on Sharing of Clinical Study 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)

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
Layout table for MeSH terms
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