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

Lymphoma, Non-Hodgkin Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05219513
• Other study ID #: BP43131
• Status: Recruiting
• Phase: Phase 1
• Start date: February 18, 2022
• Est. completion date: April 30, 2025

Study information

• Verified date: June 2024
• Source: Hoffmann-La Roche
• Contact: Reference Study ID Number: BP43131 https://forpatients.roche.com
• Phone: 888-662-6728 (U.S. and Canada)
• Email: global-roche-genentech-trials[@]gene.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 200
• Est. completion date: April 30, 2025
• Est. primary completion date: April 30, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Lymphoma
• Lymphoma, B-Cell
• Lymphoma, Non-Hodgkin

Intervention

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

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

United States,  Australia,  Denmark,  France,  Italy,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)
Primary	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	Maximum concentration (Cmax) of RO7443904		Up to 9 months
Secondary	Area under the curve (AUC) of RO7443904		Up to 9 months
Secondary	Clearance (CL) of RO7443904		Up to 9 months
Secondary	Volume of distribution (Vd) of RO7443904		Up to 9 months
Secondary	Half-life (t1/2) of RO7443904		Up to 9 months
Secondary	Percentage of Participants with RO7443904 anti-drug antibodies (ADAs) during the study relative to the prevalence of ADA at baseline		Up to 9 months
Secondary	Time to maximum concentration (Tmax) of RO7443904		Up to 9 months