A Dose Escalation Study of Glofitamab (RO7082859) as a Single Agent and in Combination With Obinutuzumab, Administered After a Fixed, Single Pre-Treatment Dose of Obinutuzumab in Participants With Relapsed/Refractory B-Cell Non-Hodgkin's Lymphoma

Official Title

A Multicentre, Open-Label, Phase I/II Study to Evaluate the Safety, Efficacy, Tolerability and Pharmacokinetics of Escalating Doses of Glofitamab (RO7082859) as a Single Agent and in Combination With Obinutuzumab Administered After a Fixed, Single Dose Pre-Treatment of Obinutuzumab (Gazyva®/Gazyvaro™) in Patients With Relapsed/Refractory B-Cell Non-Hodgkin's Lymphoma

Summary:

This is a Phase I/II, multicentre, open-label, dose-escalation study designed to evaluate the efficacy, safety, tolerability and pharmacokinetics (PK) of a novel T-Cell bispecific (TCB), glofitamab, administered by intravenous (IV) infusion as a single agent and in combination with obinutuzumab, following pre-treatment with a one-time, fixed dose of obinutuzumab. This entry-to-human study is divided in 3 parts: dose escalation (Parts I and II) and dose expansion (Part III). Single-participant dose-escalation cohorts will be used in Part I, followed by conversion to multiple participant dose-escalation cohorts (Part II), in order to define a tentative maximum tolerated dose (MTD) or optimal biological dose (OBD). The expansion cohorts (Part III) will be initiated when the tentative MTD/OBD is defined, to further evaluate the safety, PK and therapeutic activity of glofitamab.

Trial Description

Primary Outcome:

• Part I and II: Percentage of Participants With Dose Limiting Toxicities (DLTs)
• Part I, II and III: Percentage of Participants With Adverse Events (AEs)
• Part II: MTD or OBD of Glofitamab
• Part II: Recommended Phase II Dose (RP2D) of Glofitamab
• Part III: Complete Response (CR) Rate as Assessed by Independent Review Committee (IRC) According to Standard Non-Hodgkin's Lymphoma (NHL) Response Criteria (Lugano Classification)
• Part I, II and III: Area Under the Serum Concentration Versus Time Curve (AUC) of Glofitamab
• Part I, II and III: Maximum Serum Concentration (Cmax) of Glofitamab
• Part I, II and III: Minimum Serum Concentration (Cmin) of Glofitamab
• Part I, II and III: Clearance (CL) of Glofitamab
• Part I, II and III: Volume of Distribution at Steady-State (Vss) of Glofitamab
• Part I, II and III: Half-Life (t1/2) of Glofitamab

• Part I, II and III: Cmax of Obinutuzumab
• Part I, II and III: Cmin of Obinutuzumab
• Part I, II and III: Anti-Drug Antibodies (ADA) to Glofitamab
• Parts I and II: Percentage of Participants With Overall Response (Partial Response [PR] or Complete Response [CR]) as Determined by the Lugano Classification
• Part I, II and III: Percentage of Participants With PR or CR (Overall Response Rate) as Determined by the Lugano Classifications
• Part I, II and III: Duration of Response (DOR) as Determined by the Lugano Classification
• Part I, II and III: Duration of Complete Response (DOCR) as Determined by the Lugano Classification
• Part I, II and III: Progression-Free Survival (PFS) as Determined by the Lugano Classification
• Overall Survival (OS)
• Time to First Overall Response (TFOR)
• Time to First Complete Response (TFCR)
• Health Related Quality of Life (HRQoL) as Assessed by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30)
• HRQoL as Assessed by the Functional Assessment of Cancer Therapy-Lymphoma (FACT-Lym) Lymphoma Scale

View this trial on ClinicalTrials.gov