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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT05219513




Registration number
NCT05219513
Ethics application status
Date submitted
23/11/2021
Date registered
2/02/2022
Date last updated
23/08/2024

Titles & IDs
Public title
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
Scientific 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
Secondary ID [1] 0 0
BP43131
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Lymphoma, Non-Hodgkin 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - High grade lymphoma
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - Low grade lymphoma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - RO7443904
Treatment: Drugs - Glofitamab
Treatment: Drugs - Obinutuzumab
Treatment: Drugs - Tocilizumab

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.

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.


Treatment: Drugs: 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).

Treatment: Drugs: 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).

Treatment: Drugs: 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).

Treatment: Drugs: Tocilizumab
Tocilizumab will be administered as necessary to treat cytokine release syndrome (CRS).
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Nature and frequency of dose-limiting toxicities (DLTs)
Timepoint [1] 0 0
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 outcome [2] 0 0
Incidence, nature, and severity of AEs
Timepoint [2] 0 0
Up to 4 weeks after the last study treatment dose
Secondary outcome [1] 0 0
Maximum concentration (Cmax) of RO7443904
Timepoint [1] 0 0
Up to 9 months
Secondary outcome [2] 0 0
Area under the curve (AUC) of RO7443904
Timepoint [2] 0 0
Up to 9 months
Secondary outcome [3] 0 0
Clearance (CL) of RO7443904
Timepoint [3] 0 0
Up to 9 months
Secondary outcome [4] 0 0
Volume of distribution (Vd) of RO7443904
Timepoint [4] 0 0
Up to 9 months
Secondary outcome [5] 0 0
Half-life (t1/2) of RO7443904
Timepoint [5] 0 0
Up to 9 months
Secondary outcome [6] 0 0
Percentage of Participants with RO7443904 anti-drug antibodies (ADAs) during the study relative to the prevalence of ADA at baseline
Timepoint [6] 0 0
Up to 9 months
Secondary outcome [7] 0 0
Time to maximum concentration (Tmax) of RO7443904
Timepoint [7] 0 0
Up to 9 months

Eligibility
Key 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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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 design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Stopped early
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
18/02/2022
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
17/07/2024
Sample size
Target
Accrual to date
Final
53
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
Peter MacCallum Cancer Centre; Department of Haematology - Melbourne
Recruitment postcode(s) [1] 0 0
3002 - Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
New York
Country [2] 0 0
United States of America
State/province [2] 0 0
Ohio
Country [3] 0 0
United States of America
State/province [3] 0 0
Pennsylvania
Country [4] 0 0
Denmark
State/province [4] 0 0
København Ø
Country [5] 0 0
France
State/province [5] 0 0
Lille
Country [6] 0 0
Italy
State/province [6] 0 0
Lombardia
Country [7] 0 0
United Kingdom
State/province [7] 0 0
Leicester

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Hoffmann-La Roche
Address
Country

Ethics approval
Ethics application status

Summary
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).
Trial website
https://clinicaltrials.gov/study/NCT05219513
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Clinical Trials
Address 0 0
Hoffmann-La Roche
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Reference Study ID Number: BP43131 https://forpatients.roche.com/
Address 0 0
Country 0 0
Phone 0 0
888-662-6728 (U.S. and Canada)
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT05219513