Evaluate Optimization of CRS Profile for Glofit Monotherapy and Glofit+GemOx in R/R Aggressive B-NHL

NCT06806033 | Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: GO454342024-516791-15-00
• Study Type: interventional
• Target: 130
• Locations: 7 countries
• Sites: 53

Brief Summary

This Phase II trial evaluates the optimization of the cytokine release syndrome (CRS) profile for glofitamab in combination with gemcitabine and oxaliplatin (Glofit-GemOx) followed by glofitamab monotherapy treatment regimen (Cohort A), and for glofitamab monotherapy (Cohort B) in participants with relapsed or refractory aggressive B-cell Non-Hodgkin's lymphoma. The study utilizes an optimized steroid premedication regimen and monitoring schedule specifically designed to enable the administration of the treatment regimen in an outpatient setting.

Conditions

Relapsed or Refractory Aggressive B-Cell Non-Hodgkins Lymphoma

Keywords

Phase 2; Outpatient study; Open-label; Glofitamab; Gemcitabine; Oxaliplatin; Obinutuzumab; GemOx; Glofit-GemOx; Bispecific antibody; Aggressive B-cell Non-Hodgkin's lymphoma; Diffuse Large B-Cell Lymphoma (DLBCL); DLBCL NOS (Not Otherwise Specified); High-Grade B-Cell Lymphoma (HGBL); HGBL NOS; Transformed follicular lymphoma; DLBCL/HGBL with MYC and BCL2 rearrangements; Double-hit lymphoma; Relapsed or Refractory (R/R); Non-Hodgkin Lymphoma (NHL); Cytokine Release Syndrome (CRS); CRS optimization; Step-up dosing

Outcome Measures

Primary Outcomes (1)

• Incidence of Cytokine Release Syndrome (CRS)

  Up to approximately 5 years

Secondary Outcomes (9)

• Incidence of Serious Cytokine Release Syndrome (CRS) Events

  Up to approximately 5 years

• CRS Frequency Relative to the Start of Glofitamab Infusions

  Up to approximately 5 years

• Incidence and Severity of Adverse Events (AEs)

  Up to approximately 5 years

• Complete Response (CR) Rate as Determined by Independent Review Facility (IRF) and the Investigator

  Up to approximately 5 years

• Overall Response Rate (ORR) as Determined by IRF and the Investigator

  Up to approximately 5 years

Study Arms (2)

Cohort A: Glofit-GemOx Combination therapy

EXPERIMENTAL

Participants with R/R aggressive B-cell Non-Hodgkin's Lymphoma will receive obinutuzumab pre-treatment, followed by glofitamab + gemcitabine + oxaliplatin, followed by glofitamab monotherapy.

Drug: Obinutuzumab; Drug: Glofitamab; Drug: Gemcitabine; Drug: Oxaliplatin

Cohort B: Glofitamab Monotherapy

EXPERIMENTAL

Participants with R/R aggressive B-cell Non-Hodgkin's Lymphoma will receive obinutuzumab pre-treatment, followed by glofitamab monotherapy.

Drug: Obinutuzumab; Drug: Glofitamab

Interventions

Obinutuzumab DRUG

Participants will receive intravenous (IV) obinutuzumab 7 days prior to the first dose of glofitamab.

Also known as: RO5072759

Cohort A: Glofit-GemOx Combination therapy; Cohort B: Glofitamab Monotherapy

Glofitamab DRUG

Participants will receive IV glofitamab, both in combination with gemcitabine and oxaliplatin and as monotherapy, for up to 12 cycles (cycle length = 21 days).

Also known as: RO7082859

Cohort A: Glofit-GemOx Combination therapy; Cohort B: Glofitamab Monotherapy

Gemcitabine DRUG

Participants will receive IV gemcitabine in combination with glofitamab and oxaliplatin for up to 8 cycles (cycles length = 21 days).

Cohort A: Glofit-GemOx Combination therapy

Oxaliplatin DRUG

Participants will receive IV oxaliplatin in combination with glofitamab and gemcitabine for up to 8 cycles (cycle length = 21 days).

Cohort A: Glofit-GemOx Combination therapy

Eligibility Criteria

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

You may qualify if:

• Life expectancy \>= 12 weeks.
• For participants in the Glofit-GemOx combination therapy cohort (Cohort A) and the glofitamab monotherapy cohort (Cohort B), participant with histologically confirmed diffuse large B-cell lymphoma, (de novo or transformed from a follicular lymphoma (FL); participants with transformed FL must be relapsed or refractory (R/R) to standard therapies of transformed FL) with one of the following diagnoses according to World Health Organization, fifth edition (Alaggio et al. 2022). A fresh biopsy at study entry is not mandated. The histology can be confirmed based on fresh biopsy, or pathology report from a previous biopsy or an assessment of archival tumor tissue.
• Diffuse Large B-Cell Lymphoma (DLBCL) not otherwise specified (NOS).
• High-Grade B-Cell Lymphoma (HGBL), NOS.
• DLBCL/HGBL with myelocytomatosis proto-oncogene (MYC) and B-cell lymphoma 2 (BCL2) rearrangements.
• R/R disease, defined as: relapsed = disease that has recurred following a response that lasted \>/= 6 months after completion of the last line of therapy; refractory = disease that did not respond to or that progressed \< 6 months after completion of the last line of therapy.
• At least one line of prior systemic therapy.
• Participants who have failed one prior line of therapy (eligible to Cohort A) must not be a candidate for high-dose chemotherapy followed by autologous stem cell transplant.
• At least one bi-dimensionally measurable (\> 1.5 cm) nodal lesion, or one bi-dimensionally measurable (\> 1 cm) extranodal lesion, as measured on CT scan.
• Eastern Cooperative Oncology Group (ECOG) status of 0, 1, or 2.
• According to the investigator's judgment, participants should be able to receive the step-up dose regimen in an outpatient setting.

You may not qualify if:

• Prior enrollment in Studies GO41943 (NCT04313608), GO41944 (STARGLO; NCT04408638), or Study GO44900 (NCT06624085).
• Participant has failed only one prior line of therapy and is a candidate for stem cell transplantation.
• Any history of Waldenstrom's macroglobulinemia.
• Primary mediastinal B-cell lymphoma.
• History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies (or recombinant antibody-related fusion proteins) or known sensitivity or allergy to murine products.
• Contraindication to obinutuzumab, gemcitabine or oxaliplatin, or tocilizumab. For participants in the monotherapy cohort (Cohort B), participants with contraindication to obinutuzumab or tocilizumab will be excluded.
• Prior treatment with glofitamab or other bispecific antibodies targeting both CD20 and CD3.
• For the Glofit-GemOx combination therapy cohort (Cohort A), prior treatment with gemcitabine or oxaliplatin.
• For the Glofit-GemOx combination therapy cohort (Cohort A), peripheral neuropathy or paresthesia assessed to be Grade \>= 2 according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0 at enrolment.
• Treatment with radiotherapy, chemotherapy, immunotherapy, immunosuppressive therapy, or any investigational agent for the purposes of treating cancer within 2 weeks prior to first study treatment.
• Treatment with monoclonal antibodies for the purposes of treating cancer within 4 weeks prior to first study treatment.
• Primary or secondary CNS lymphoma at the time of recruitment.
• Prior CNS involvement that has been definitively treated and confirmed via magnetic resonance imaging (MRI) or cerebrospinal fluid analysis to be in complete remission is permissible.
• Current or history of CNS disease, such as stroke, epilepsy, CNS vasculitis, or neurodegenerative disease.
• History of other primary malignancy, with exceptions defined by the protocol.

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (53)

Alaska Oncology & Hematology, LLC

Anchorage, Alaska, 99508, United States

RECRUITING

Community Cancer Institute (CCI)

Clovis, California, 93611, United States

RECRUITING

Providence Medical Foundation

Fullerton, California, 92835, United States

RECRUITING

Los Angeles Cancer Network

Glendale, California, 91204, United States

RECRUITING

Valkyrie Clinical Trials

Los Angeles, California, 90067, United States

RECRUITING

Valkyrie Clinical Trials

Panorama City, California, 91402, United States

RECRUITING

Zuckerberg San Francisco General Hospital

San Francisco, California, 94110, United States

RECRUITING

The Lundquist Institute for BioMedical Innovation at Harbor-UCLA Medical Cente

Torrance, California, 90502-2006, United States

RECRUITING

Rocky Mountain Cancer Centers, LLP

Aurora, Colorado, 80012, United States

RECRUITING

North Florida/ South Georgia VA Medical Center

Gainesville, Florida, 32608, United States

RECRUITING

Mount Sinai Comprehensive Cancer Center

Miami, Florida, 33140, United States

RECRUITING

Orlando Health Cancer Institute

Orlando, Florida, 32806, United States

RECRUITING

St Luke?s Cancer Institute

Boise, Idaho, 83712, United States

RECRUITING

Cancer Care Specialists of Central Illinois

Swansea, Illinois, 62226, United States

RECRUITING

Mission Blood and Cancer - MercyOne Cancer Center

Waukee, Iowa, 50263, United States

RECRUITING

University of Kentucky - Markey Cancer Center

Lexington, Kentucky, 40536, United States

RECRUITING

Mary Bird Perkins Cancer Ctr

Baton Rouge, Louisiana, 70809, United States

RECRUITING

Boston Medical Center

Boston, Massachusetts, 02118, United States

RECRUITING

Corewell Health

Grand Rapids, Michigan, 49503, United States

RECRUITING

Nebraska Cancer Specialists

Omaha, Nebraska, 68130, United States

RECRUITING

New York Oncology Hematology, P.C.

Albany, New York, 12206, United States

RECRUITING

Hematology Oncology Associates of Central New York

East Syracuse, New York, 13057, United States

RECRUITING

Oncology Associates of Oregon, P.C

Eugene, Oregon, 97401, United States

RECRUITING

Providence Portland Medical Center

Portland, Oregon, 97213, United States

RECRUITING

Providence St. Vincent Medical Center

Portland, Oregon, 97225, United States

RECRUITING

Tennessee Oncology

Chattanooga, Tennessee, 37403, United States

RECRUITING

Tennessee Oncology

Nashville, Tennessee, 37203, United States

RECRUITING

Baylor Scott & White Health

Temple, Texas, 76502, United States

RECRUITING

Texas Oncology - Gulf Coast

The Woodlands, Texas, 77380, United States

RECRUITING

Texas Oncology- Northeast Texas

Tyler, Texas, 75702, United States

RECRUITING

Virginia Cancer Specialists, PC

Fairfax, Virginia, 22031, United States

RECRUITING

Virginia Oncology Associates - Virginia Beach

Virginia Beach, Virginia, 23456, United States

RECRUITING

Northwest Medical Specialties

Tacoma, Washington, 98405, United States

RECRUITING

Epworth Hospital

East Melbourne, Victoria, 3002, Australia

ACTIVE NOT RECRUITING

Arthur J.E. Child Comprehensive Cancer Center

Calgary, Alberta, T2N 5G2, Canada

RECRUITING

CancerCare Manitoba (CCMB)

Winnipeg, Manitoba, R3E 0V9, Canada

RECRUITING

CHU de Grenoble

La Tronche, 38700, France

RECRUITING

Chu de Montpellier-St Eloi

Montpellier, 34295, France

RECRUITING

CHU de Bordeaux

Pessac, 33600, France

RECRUITING

CHU DE RENNES - CHU Pontchaillou

Rennes, 35033, France

WITHDRAWN

Chu De Tours

Tours, 37000, France

RECRUITING

CAMPUS BENJAMIN FRANKLIN CharitéCentrum 14 Med.Klinik f.Hämatologie u.Onkologie

Berlin, 12200, Germany

WITHDRAWN

Charite-Universitaetsmedizin Berlin - Campus Virchow-Klinikum (CVK)

Berlin, 13353, Germany

WITHDRAWN

Universitätsklinikum Köln

Cologne, 50937, Germany

RECRUITING

Otto von Guericke Uni Magdeburg Uniklinik

Magdeburg, 39120, Germany

RECRUITING

Istituto Nazionale Tumori Irccs Fondazione g. Pascale

Naples, Campania, 80131, Italy

ACTIVE NOT RECRUITING

IRCCS Istituto Romagnolo per lo studio dei tumori "Dino Amadori"

Meldola, Emilia-Romagna, 47014, Italy

ACTIVE NOT RECRUITING

A.O. Spedali Civili Di Brescia-P.O. Spedali Civili

Brescia, Lombardy, 25123, Italy

ACTIVE NOT RECRUITING

Irccs Istituto Europeo Di Oncologia (IEO)

Milan, Lombardy, 20141, Italy

ACTIVE NOT RECRUITING

Istituto Clinico Humanitas

Rozzano, Lombardy, 20089, Italy

ACTIVE NOT RECRUITING

Seoul National University Bundang Hospital

Seongnam-si, 463-707, South Korea

ACTIVE NOT RECRUITING

Seoul National University Hospital

Seoul, 03080, South Korea

WITHDRAWN

Asan Medical Center

Seoul, 05505, South Korea

ACTIVE NOT RECRUITING

Related Links

• Please use this form to submit your questions for a faster response: https://www.gene.com/contact-us/submit-medical-inquiry. Do not include or attach any medical records when emailing or completing the form. A nurse will respond within 24 business hours.

MeSH Terms

Conditions

Recurrence; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Non-Hodgkin; Cytokine Release Syndrome

Interventions

obinutuzumab; glofitamab; Gemcitabine; Oxaliplatin

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Lymphoma, B-Cell; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Systemic Inflammatory Response Syndrome; Inflammation; Shock

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Coordination Complexes; Organic Chemicals

Study Officials

• Study Director

  Hoffmann-La Roche

  STUDY DIRECTOR

Central Study Contacts

Reference Study ID Number: GO45434 https://forpatients.roche.com/ No attachments to email below.

CONTACT

888-662-6728 (U.S. Only); global-roche-genentech-trials@gene.com

Fastest response: use the inquiry form. https://www.gene.com/contact-us/submit-medical-inquiry

CONTACT

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 21, 2025
• First Posted: February 3, 2025
• Study Start: March 5, 2025
• Primary Completion (Estimated): January 31, 2027
• Study Completion (Estimated): March 30, 2029
• Last Updated: September 11, 2026

Record last verified: 2026-09

Data Sharing

• IPD Sharing: Will share

Locations

IT (5); US (33); DE (4); KR (3); AU (1); FR (5); CA (2)