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

  • STATUS
    Recruiting
  • days left to enroll
    29
  • participants needed
    420
  • sponsor
    Hoffmann-La Roche
Updated on 28 October 2022
ct scan
cancer
hodgkin's disease
b-cell lymphoma
obinutuzumab
non-hodgkin's lymphoma refractory

Summary

This is a phase I/II, 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).

Details
Condition Lymphoma, Non-Hodgkin
Treatment Tocilizumab, Obinutuzumab, RO7082859, RO7227166, Glofitamab
Clinical Study IdentifierNCT04077723
SponsorHoffmann-La Roche
Last Modified on28 October 2022

Eligibility

Yes No Not Sure

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 two prior treatment regimens; 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 3.5 months after the last dose of RO7227166, 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

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 shorter, 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 shorter, 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) within two weeks prior to Gpt, 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
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