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

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

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).

Study Overview

• Status: Terminated
• Conditions: Lymphoma, Non-Hodgkin
• Intervention / Treatment: Drug: Tocilizumab; Drug: Glofitamab; Drug: Obinutuzumab; Drug: RO7443904

• Study Type: Interventional
• Enrollment (Actual): 53
• Phase: Phase 1

Contacts and Locations

Study Locations

• Australia
  • Victoria
    • Melbourne, Victoria, Australia, 3002
      • Peter MacCallum Cancer Centre; Department of Haematology
• Denmark
  • København Ø, Denmark, 2100
    • Rigshospitalet; Hæmatologisk Klinik, Klinisk Afprøvnings Team KAT
• France
  • Lille, France, 59037
    • CHRU Lille - Hôpital Claude Huriez; Service des Maladies du Sang
• Italy
  • Lombardia
    • Bergamo, Lombardia, Italy, 24127
      • ASST PAPA GIOVANNI XXIII; Ematologia
    • Rozzano, Lombardia, Italy, 20089
      • Istituto Clinico Humanitas;U.O. Oncologia Medica Ed Ematologia
• United Kingdom
  • Leicester, United Kingdom, LE1 5WW
    • Leicester Royal Infirmary; Dept of Haematology
• United States
  • New York
    • New York, New York, United States, 10065
      • MSKCC
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Foundation; Hematology and Oncology
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

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)
• Autologous SCT within 100 days prior to obinutuzumab infusion
• Autoimmune disease in active phase or exacerbation/flare within at least 6 months of enrollment
• History of immune deficiency disease that increases the risk of infection
• History of contraindication and/or severe allergic or anaphylactic reactions to monoclonal antibody therapy and/or prophylactic drugs used for cytokine release syndrome (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 affect compliance with the protocol or interpretation of results
• 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 for reasons other than anticancer therapy within the last 6 months of enrollment with the exception of corticosteroid treatment <= 25 mg/day prednisone or equivalent
• History of illicit drug or alcohol abuse within 12 months prior to screening, in the Investigator's judgment
• Any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that would contraindicate the use of an investigational drug

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Drug: Tocilizumab; Tocilizumab will be administered as necessary to treat cytokine release syndrome (CRS).; Other Names: Actemra; Drug: Glofitamab; Glofitamab will be administered through IV infusion starting with step-up dosing (2.5 mg/10 mg/30 mg) on C1D1, C1D8, and C2D1. Starting in Cycle 3, glofitamab will be given in 30 mg doses every three weeks (Q3W) with RO7443904, for up to 12 cycles (Cycle = 21 days).; Other Names: RO7082859; Drug: Obinutuzumab; Obinutuzumab will be administered once through IV infusion, at a 1 g dose in Cycle 1, on either Day -7, -4, or -3 (C1D-7, C1D-4, C1D-3).; Drug: RO7443904; RO7443904 will be administered by subcutaneous (SC) or IV infusion on Cycle (C) 1 Day (D) 10, C2D3, and C2D8. From C3 onward, RO7443904 will be given every 3 weeks (Q3W), for up to 12 cycles (C = 21 days).
Experimental: 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.	Drug: Tocilizumab; Tocilizumab will be administered as necessary to treat cytokine release syndrome (CRS).; Other Names: Actemra; Drug: Glofitamab; Glofitamab will be administered through IV infusion starting with step-up dosing (2.5 mg/10 mg/30 mg) on C1D1, C1D8, and C2D1. Starting in Cycle 3, glofitamab will be given in 30 mg doses every three weeks (Q3W) with RO7443904, for up to 12 cycles (Cycle = 21 days).; Other Names: RO7082859; Drug: RO7443904; RO7443904 will be administered by subcutaneous (SC) or IV infusion on Cycle (C) 1 Day (D) 10, C2D3, and C2D8. From C3 onward, RO7443904 will be given every 3 weeks (Q3W), for up to 12 cycles (C = 21 days).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Nature and frequency of dose-limiting toxicities (DLTs)		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)
Incidence, nature, and severity of AEs	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	Up to 4 weeks after the last study treatment dose

Secondary Outcome Measures

Outcome Measure	Time Frame
Maximum concentration (Cmax) of RO7443904	Up to 9 months
Area under the curve (AUC) of RO7443904	Up to 9 months
Clearance (CL) of RO7443904	Up to 9 months
Volume of distribution (Vd) of RO7443904	Up to 9 months
Half-life (t1/2) 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
Time to maximum concentration (Tmax) of RO7443904	Up to 9 months

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche
• Investigators: Study Director: Clinical Trials, Hoffmann-La Roche

Study record dates

Study Major Dates

• Study Start (Actual): February 18, 2022
• Primary Completion (Actual): July 17, 2024
• Study Completion (Actual): July 17, 2024

Study Registration Dates

• First Submitted: November 23, 2021
• First Submitted That Met QC Criteria: January 20, 2022
• First Posted (Actual): February 2, 2022

Study Record Updates

• Last Update Posted (Actual): August 23, 2024
• Last Update Submitted That Met QC Criteria: August 22, 2024
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma; Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Antineoplastic Agents; Antineoplastic Agents, Immunological; Obinutuzumab
• Other Study ID Numbers: BP43131

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.clinicalstudydatarequest.com). Further details on Roche's criteria for eligible studies are available here (https://clinicalstudydatarequest.com/Study-Sponsors/Study-Sponsors-Roche.aspx). For further details on Roche's Global Policy on Sharing of Clinical Study Information and how to request access to related clinical study documents, see here (https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No