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

NCT05219513 | Terminated Phase 1 FDA Drug

• 1 other identifier: BP43131
• Study Type: interventional
• Target: 53
• Locations: 6 countries
• Sites: 9

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

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (7)

• 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

Study Arms (2)

Parts I-III: Dose-escalation of RO7443904

EXPERIMENTAL

The dose-escalation of RO7443904 and glofitamab will take place every three weeks (Q3W) with obinutuzumab pre-treatment.

Drug: RO7443904; Drug: Glofitamab; Drug: Obinutuzumab; Drug: Tocilizumab

Part IV: Dose-expansion of RO7443904

EXPERIMENTAL

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: RO7443904; Drug: Glofitamab; Drug: Tocilizumab

Interventions

RO7443904 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).

Part IV: Dose-expansion of RO7443904; Parts I-III: Dose-escalation of RO7443904

Glofitamab 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).

Also known as: RO7082859

Part IV: Dose-expansion of RO7443904; Parts I-III: Dose-escalation of RO7443904

Obinutuzumab 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).

Parts I-III: Dose-escalation of RO7443904

Tocilizumab DRUG

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

Also known as: Actemra

Part IV: Dose-expansion of RO7443904; Parts I-III: Dose-escalation of RO7443904

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (9)

MSKCC

New York, New York, 10065, United States

Location

Cleveland Clinic Foundation; Hematology and Oncology

Cleveland, Ohio, 44195, United States

Location

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Peter MacCallum Cancer Centre; Department of Haematology

Melbourne, Victoria, 3002, Australia

Location

Rigshospitalet; Hæmatologisk Klinik, Klinisk Afprøvnings Team KAT

København Ø, 2100, Denmark

Location

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

Lille, 59037, France

Location

ASST PAPA GIOVANNI XXIII; Ematologia

Bergamo, Lombardy, 24127, Italy

Location

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

Rozzano, Lombardy, 20089, Italy

Location

Leicester Royal Infirmary; Dept of Haematology

Leicester, LE1 5WW, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 38437725 DERIVED

MeSH Terms

Conditions

Lymphoma, Non-Hodgkin

Interventions

glofitamab; obinutuzumab; tocilizumab

Condition Hierarchy (Ancestors)

Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 23, 2021
• First Posted: February 2, 2022
• Study Start: February 18, 2022
• Primary Completion: July 17, 2024
• Study Completion: July 17, 2024
• Last Updated: August 23, 2024

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will not share

Locations

IT (2); FR (1); GB (1); US (3); DK (1); AU (1)