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

NCT ID: NCT05219513

Last Updated: 2024-08-23

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 53 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-02-18
• Study Completion Date: 2024-07-17

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).

Conditions

Lymphoma, Non-Hodgkin

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

RO7443904

Intervention Type: DRUG

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).

Glofitamab

Intervention Type: DRUG

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).

Obinutuzumab

Intervention Type: DRUG

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).

Tocilizumab

Intervention Type: DRUG

Tocilizumab will be administered as necessary to treat cytokine release syndrome (CRS).

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.

Group Type: EXPERIMENTAL

RO7443904

Intervention Type: DRUG

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).

Glofitamab

Intervention Type: DRUG

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).

Tocilizumab

Intervention Type: DRUG

Tocilizumab will be administered as necessary to treat cytokine release syndrome (CRS).

Interventions

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).

Intervention Type: 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).

Intervention Type: 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).

Intervention Type: DRUG

Tocilizumab

Tocilizumab will be administered as necessary to treat cytokine release syndrome (CRS).

Intervention Type: DRUG

Other Intervention Names

RO7082859; Actemra

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
• 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hoffmann-La Roche

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Trials

Role: STUDY_DIRECTOR

Hoffmann-La Roche

Locations

MSKCC

New York, New York, United States

Cleveland Clinic Foundation; Hematology and Oncology

Cleveland, Ohio, United States

University of Pennsylvania

Philadelphia, Pennsylvania, United States

Peter MacCallum Cancer Centre; Department of Haematology

Melbourne, Victoria, Australia

Rigshospitalet; Hæmatologisk Klinik, Klinisk Afprøvnings Team KAT

København Ø, , Denmark

CHRU Lille - Hôpital Claude Huriez; Service des Maladies du Sang

Lille, , France

ASST PAPA GIOVANNI XXIII; Ematologia

Bergamo, Lombardy, Italy

Istituto Clinico Humanitas;U.O. Oncologia Medica Ed Ematologia

Rozzano, Lombardy, Italy

Leicester Royal Infirmary; Dept of Haematology

Leicester, , United Kingdom

Countries

United States; Australia; Denmark; France; Italy; United Kingdom

References

Sam J, Hofer T, Kuettel C, Claus C, Thom J, Herter S, Georges G, Korfi K, Lechmann M, Eigenmann MJ, Marbach D, Jamois C, Lechner K, Krishnan SM, Gaillard B, Marinho J, Kronenberg S, Kunz L, Wilson S, Briner S, Gebhardt S, Varol A, Appelt B, Nicolini V, Speziale D, Bez M, Bommer E, Eckmann J, Hage C, Limani F, Jenni S, Schoenle A, Le Clech M, Vallier JP, Colombetti S, Bacac M, Gasser S, Klein C, Umana P. CD19-CD28: an affinity-optimized CD28 agonist for combination with glofitamab (CD20-TCB) as off-the-shelf immunotherapy. Blood. 2024 May 23;143(21):2152-2165. doi: 10.1182/blood.2023023381.

Reference Type: DERIVED

PMID: 38437725 (View on PubMed)

Other Identifiers

BP43131

Identifier Type: -

Identifier Source: org_study_id