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
Overview
- Phase
- Phase 1
- Intervention
- Tocilizumab
- Conditions
- Lymphoma, Non-Hodgkin
- Sponsor
- Hoffmann-La Roche
- Enrollment
- 53
- Locations
- 9
- Primary Endpoint
- Incidence, nature, and severity of AEs
- Status
- Terminated
- Last Updated
- last year
Overview
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).
Investigators
Eligibility 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
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 known acute bacterial, viral, or fungal infection 72 hours prior to 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 with prior immunotherapeutic agents
- •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)
Arms & Interventions
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.
Intervention: Tocilizumab
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.
Intervention: RO7443904
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.
Intervention: Glofitamab
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.
Intervention: Obinutuzumab
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.
Intervention: RO7443904
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.
Intervention: Glofitamab
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.
Intervention: Tocilizumab
Outcomes
Primary Outcomes
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
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)
Secondary Outcomes
- Clearance (CL) of RO7443904(Up to 9 months)
- Volume of distribution (Vd) of RO7443904(Up to 9 months)
- Percentage of Participants with RO7443904 anti-drug antibodies (ADAs) during the study relative to the prevalence of ADA at baseline(Up to 9 months)
- Maximum concentration (Cmax) of RO7443904(Up to 9 months)
- Time to maximum concentration (Tmax) of RO7443904(Up to 9 months)
- Area under the curve (AUC) of RO7443904(Up to 9 months)
- Half-life (t1/2) of RO7443904(Up to 9 months)