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Lymphoma, Non-HodgkinPhase 1NCT05219513

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

A Phase 1 study testing RO7443904, Glofitamab and Obinutuzumab in people with Lymphoma, Non-Hodgkin, run by Hoffmann-La Roche at 9 sites in 6 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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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… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Lymphoma, Non-Hodgkin
What is being tested?
RO7443904, Glofitamab and Obinutuzumab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
53 participants
Where
9 sitesin 6 countries
Study dates
18 Feb 2022to 17 Jul 2024
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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

Who cannot join

  • 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
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  • 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

Trial locations and contacts

9 sites in 6 countries.

9 sites in 6 countries

United States3 sites

  • Cleveland Clinic Foundation; Hematology and Oncology

    Cleveland, Ohio, 44195

  • MSKCC

    New York, New York, 10065

  • University of Pennsylvania

    Philadelphia, Pennsylvania, 19104

Other trials in United States

Italy2 sites

  • ASST PAPA GIOVANNI XXIII; Ematologia

    Bergamo, Lombardy, 24127

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

    Rozzano, Lombardy, 20089

Other trials in Italy

Australia1 site

  • Peter MacCallum Cancer Centre; Department of Haematology

    Melbourne, Victoria, 3002

Other trials in Australia

Denmark1 site

  • Rigshospitalet; Hæmatologisk Klinik, Klinisk Afprøvnings Team KAT

    København Ø, 2100

Other trials in Denmark

France1 site

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

    Lille, 59037

Other trials in France

United Kingdom1 site

  • Leicester Royal Infirmary; Dept of Haematology

    Leicester, LE1 5WW

Other trials in United Kingdom

About this study

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

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).

Being tested
RO7443904, Glofitamab, Obinutuzumab, Tocilizumab
Medical subject headings
Lymphoma, Non-Hodgkin

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • RO7443904Drug

    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).

  • GlofitamabDrug

    Also called RO7082859

    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).

  • ObinutuzumabDrug

    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).

  • TocilizumabDrug

    Also called Actemra

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

Study groups in NCT05219513
Study groupRoleWhat they receive
Parts I-III: Dose-escalation of RO7443904ExperimentalThe dose-escalation of RO7443904 and glofitamab will take place every three weeks (Q3W) with obinutuzumab pre-treatment.
Receives: Drug: RO7443904; Drug: Glofitamab; Drug: Obinutuzumab; Drug: Tocilizumab
Part IV: Dose-expansion of RO7443904ExperimentalPart 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.
Receives: Drug: RO7443904; Drug: Glofitamab; Drug: Tocilizumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Nature and frequency of dose-limiting toxicities (DLTs)

    Measured: 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)

  2. 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

    Measured: Up to 4 weeks after the last study treatment dose

Secondary outcomes (7)

  1. Maximum concentration (Cmax) of RO7443904

    Measured: Up to 9 months

  2. Area under the curve (AUC) of RO7443904

    Measured: Up to 9 months

  3. Clearance (CL) of RO7443904

    Measured: Up to 9 months

  4. Volume of distribution (Vd) of RO7443904

    Measured: Up to 9 months

  5. Half-life (t1/2) of RO7443904

    Measured: Up to 9 months

  6. Percentage of Participants with RO7443904 anti-drug antibodies (ADAs) during the study relative to the prevalence of ADA at baseline

    Measured: Up to 9 months

  7. Time to maximum concentration (Tmax) of RO7443904

    Measured: Up to 9 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted2 Feb 2022
  2. Study start18 Feb 2022
  3. Primary completion17 Jul 2024
  4. Study completion17 Jul 2024

Why it stopped: The study was terminated due to sponsor portfolio re-alignment.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
53 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05219513
Sponsor's protocol ID
BP43131
Status last verified
Aug 2024
First submitted
23 Nov 2021
Last updated
23 Aug 2024
Results posted
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No: 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)

Publications

  • 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.

    PubMed 38437725

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing RO7443904, Glofitamab and Obinutuzumab in people with Lymphoma, Non-Hodgkin, run by Hoffmann-La Roche at 9 sites in 6 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 11 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 23 Aug 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 9 sites in United States, Italy, Australia, Denmark, France and 1 more country. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: The study was terminated due to sponsor portfolio re-alignment.). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Nature and frequency of dose-limiting toxicities (DLTs) (time frame: 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)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05219513, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Aug 2024.

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