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

Phase 1

Terminated

• Conditions: Lymphoma, Non-Hodgkin

• Registration Number: NCT05219513
• Lead Sponsor: Hoffmann-La Roche

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2021-11-23
• Last Update Posted: 2 September 2024

Recruitment & Eligibility

• Status: Terminated
• Sex: All
• Target Recruitment: 53

Inclusion Criteria

Inclusion Criteria:<br><br> - Body weight >=40 kg<br><br> - Histologically confirmed hematological malignancy that is expected to express CD19<br> and CD20 and with clinical evidence of treatment need; 2) relapse after or failure<br> to respond to at least two prior treatment regimens; and 3) no other available<br> treatment options that are known to provide clinical benefit<br><br> - Must have at least one measurable target lesion (>=1.5 cm) in its largest dimension<br> by computed tomography (CT) scan<br><br> - Able and willing to provide a fresh tumor biopsy from a safely accessible site, per<br> Investigator's determination<br><br> - Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1<br><br> - Life expectancy of >=12 weeks<br><br> - Adequate liver, hematological and renal function<br><br> - Negative serologic or polymerase chain reaction (PCR) test results for acute or<br> chronic hepatitis B virus (HBV) infection<br><br> - Negative test results for hepatitis C virus (HCV) and HIV<br><br> - A female participant is eligible to participate if she is not pregnant, not<br> breastfeeding, and at least one of the following conditions applies: 1) Women of<br> non-childbearing potential 2) Women of childbearing potential (WOCBP), who, agree to<br> remain abstinent (refrain from heterosexual intercourse) or use of one highly<br> effective contraceptive method during the treatment period and for at least 18<br> months after obinutuzumab or 5 months after the final dose of RO7443904, 2 months<br> after final dose of glofitamab or 3 months after the final dose of tocilizumab<br><br> - Male participants must remain abstinent (refrain from heterosexual intercourse) or<br> use contraceptive measures such as a condom plus an additional contraceptive method<br> with a partner who is a WOCBP during the treatment period and for at least 3 months<br> after obinutuzumab, 5 months after the final dose of RO7443904, 2 months after the<br> final dose of glofitamab or 2 months after the final dose of tocilizumab, whichever<br> is longer<br><br>Exclusion Criteria:<br><br> - Circulating lymphoma cells, defined by out-of-range (high) absolute lymphocyte count<br> (ALC) or the presence of abnormal cells in the peripheral blood signifying<br> circulating lymphoma cells<br><br> - Participants with known acute bacterial, viral, or fungal infection 72 hours prior<br> to glofitamab infusion<br><br> - Participants with known active infection or reactivation of a latent infection<br><br> - Pregnant, breastfeeding, or intending to become pregnant during the study<br><br> - Prior treatment with systemic immunotherapeutic agents<br><br> - History of treatment-emergent, immune-related adverse events (AEs) associated with<br> prior immunotherapeutic agents<br><br> - Persistent AEs from prior anti-cancer therapy Grade >=1<br><br> - Treatment with standard radiotherapy, any chemotherapeutic agent, or treatment with<br> any other investigational or approved anti-cancer agent<br><br> - Prior solid organ transplantation<br><br> - Prior allogeneic stem cell transplant (SCT)<br><br> - Autologous SCT within 100 days prior to obinutuzumab infusion<br><br> - Autoimmune disease in active phase or exacerbation/flare within at least 6 months of<br> enrollment<br><br> - History of immune deficiency disease that increases the risk of infection<br><br> - History of contraindication and/or severe allergic or anaphylactic reactions to<br> monoclonal antibody therapy and/or prophylactic drugs used for cytokine release<br> syndrome (CRS) and tumor lysis syndrome (TLS)<br><br> - History of confirmed progressive multifocal leukoencephalopathy<br><br> - Current or past history of central nervous system (CNS) lymphoma or CNS disease<br><br> - Evidence of significant, uncontrolled concomitant diseases that could affect<br> compliance with the protocol or interpretation of results<br><br> - Major surgery or significant traumatic injury <28 days prior to the GpT infusion or<br> anticipation of the need for major surgery during study treatment<br><br> - Participants with another invasive malignancy in the last 2 years<br><br> - Significant cardiovascular disease<br><br> - Administration of a live, attenuated vaccine within 4 weeks before GpT infusion or<br> anticipation that such a live attenuated vaccine will be required during the study<br><br> - Received systemic immunosuppressive medications for reasons other than anticancer<br> therapy within the last 6 months of enrollment with the exception of corticosteroid<br> treatment <= 25 mg/day prednisone or equivalent<br><br> - History of illicit drug or alcohol abuse within 12 months prior to screening, in the<br> Investigator's judgment<br><br> - Any other diseases, metabolic dysfunction, physical examination finding, or clinical<br> laboratory finding giving reasonable suspicion of a disease or condition that would<br> contraindicate the use of an investigational drug

Exclusion Criteria

Not provided

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Nature and frequency of dose-limiting toxicities (DLTs);Incidence, nature, and severity of AEs

Secondary Outcome Measures

Name	Time	Method
Maximum concentration (Cmax) of RO7443904;Area under the curve (AUC) of RO7443904;Clearance (CL) of RO7443904;Volume of distribution (Vd) of RO7443904;Half-life (t1/2) of RO7443904;Percentage of Participants with RO7443904 anti-drug antibodies (ADAs) during the study relative to the prevalence of ADA at baseline;Time to maximum concentration (Tmax) of RO7443904