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

Last updated: August 22, 2024
Sponsor: Hoffmann-La Roche
Overall Status: Terminated

Phase

1

Condition

Lymphoma

Lymphoma, B-cell

Treatment

Tocilizumab

Obinutuzumab

RO7443904

Clinical Study ID

NCT05219513
BP43131
  • Ages > 18
  • All Genders

Study 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).

Eligibility Criteria

Inclusion

Inclusion Criteria:

  • Body weight >=40 kg

  • Histologically confirmed hematological malignancy that is expected to express CD19and CD20 and with clinical evidence of treatment need; 2) relapse after or failureto respond to at least two prior treatment regimens; and 3) no other availabletreatment options that are known to provide clinical benefit

  • Must have at least one measurable target lesion (>=1.5 cm) in its largest dimensionby computed tomography (CT) scan

  • Able and willing to provide a fresh tumor biopsy from a safely accessible site, perInvestigator'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 orchronic 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, notbreastfeeding, and at least one of the following conditions applies: 1) Women ofnon-childbearing potential 2) Women of childbearing potential (WOCBP), who, agree toremain abstinent (refrain from heterosexual intercourse) or use of one highlyeffective contraceptive method during the treatment period and for at least 18months after obinutuzumab or 5 months after the final dose of RO7443904, 2 monthsafter final dose of glofitamab or 3 months after the final dose of tocilizumab

  • Male participants must remain abstinent (refrain from heterosexual intercourse) oruse contraceptive measures such as a condom plus an additional contraceptive methodwith a partner who is a WOCBP during the treatment period and for at least 3 monthsafter obinutuzumab, 5 months after the final dose of RO7443904, 2 months after thefinal dose of glofitamab or 2 months after the final dose of tocilizumab, whicheveris longer

Exclusion

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 signifyingcirculating lymphoma cells

  • Participants with known acute bacterial, viral, or fungal infection 72 hours priorto glofitamab infusion

  • 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 withprior immunotherapeutic agents

  • Persistent AEs from prior anti-cancer therapy Grade >=1

  • Treatment with standard radiotherapy, any chemotherapeutic agent, or treatment withany 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 ofenrollment

  • History of immune deficiency disease that increases the risk of infection

  • History of contraindication and/or severe allergic or anaphylactic reactions tomonoclonal antibody therapy and/or prophylactic drugs used for cytokine releasesyndrome (CRS) and tumor lysis syndrome (TLS)

  • 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 affectcompliance with the protocol or interpretation of results

  • Major surgery or significant traumatic injury <28 days prior to the GpT infusion oranticipation 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 oranticipation that such a live attenuated vaccine will be required during the study

  • Received systemic immunosuppressive medications for reasons other than anticancertherapy within the last 6 months of enrollment with the exception of corticosteroidtreatment <= 25 mg/day prednisone or equivalent

  • History of illicit drug or alcohol abuse within 12 months prior to screening, in theInvestigator's judgment

  • Any other diseases, metabolic dysfunction, physical examination finding, or clinicallaboratory finding giving reasonable suspicion of a disease or condition that wouldcontraindicate the use of an investigational drug

Study Design

Total Participants: 53
Treatment Group(s): 4
Primary Treatment: Tocilizumab
Phase: 1
Study Start date:
February 18, 2022
Estimated Completion Date:
July 17, 2024

Connect with a study center

  • Peter MacCallum Cancer Centre; Department of Haematology

    Melbourne, Victoria 3002
    Australia

    Site Not Available

  • Rigshospitalet; Hæmatologisk Klinik, Klinisk Afprøvnings Team KAT

    København Ø, 2100
    Denmark

    Site Not Available

  • CHRU Lille - Hôpital Claude Huriez; Service des Maladies du Sang

    Lille, 59037
    France

    Site Not Available

  • ASST PAPA GIOVANNI XXIII; Ematologia

    Bergamo, Lombardia 24127
    Italy

    Site Not Available

  • Istituto Clinico Humanitas;U.O. Oncologia Medica Ed Ematologia

    Rozzano, Lombardia 20089
    Italy

    Site Not Available

  • Leicester Royal Infirmary; Dept of Haematology

    Leicester, LE1 5WW
    United Kingdom

    Site Not Available

  • MSKCC

    New York, New York 10065
    United States

    Site Not Available

  • Cleveland Clinic Foundation; Hematology and Oncology

    Cleveland, Ohio 44195
    United States

    Site Not Available

  • University of Pennsylvania

    Philadelphia, Pennsylvania 19104
    United States

    Site Not Available

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