A Study Evaluating the Efficacy, Safety, and Pharmacokinetics of Glofitamab in Combination With Rituximab Plus Ifosfamide, Carboplatin Etoposide Phosphate in Participants With Relapsed/Refractory Transplant or CAR-T Therapy Eligible Diffuse B-Cell Lymphoma

A Phase IB, Open-Label, Multicenter, Single Arm Study Evaluating the Preliminary Efficacy, Safety, and Pharmacokinetics of Glofitamab in Combination With Rituximab Plus Ifosfamide, Carboplatin Etoposide Phosphate in Patients With Relapsed/Refractory Transplant or CAR-T Therapy Eligible Diffuse B-Cell Lymphoma

The purpose of this study is to evaluate the preliminary efficacy, safety, and pharmacokinetics of glofitamab (glofit) in combination with rituximab plus ifosfamide, carboplatin, and etoposide (R-ICE) in participants with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL), who have failed one prior line of therapy incorporating an anti-cluster of differentiation (CD) 20 antibody (i.e., rituximab) and an anthracycline, and who are transplant or chimeric antigen receptor T-cell (CAR-T) therapy eligible, defined as being medically eligible for intensive platinum-based salvage therapy followed by autologous stem cell transplantation (ASCT) or for CAR-T therapy.

Study Overview

• Status: Recruiting
• Conditions: Diffuse Large B-Cell Lymphoma (DLBCL)
• Intervention / Treatment: Drug: Glofitamab; Drug: Obinutuzumab; Drug: Tocilizumab; Drug: Rituximab; Drug: Ifosfamide; Drug: Carboplatin; Drug: Etoposide

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Reference Study ID Number: GO43693 https://forpatients.roche.com/; Phone Number: 888-662-6728; Email: global-roche-genentech-trials@gene.com

Study Locations

• United States
  • California
    • Orange, California, United States, 92868
      • Active, not recruiting
      • Chao Family Comprehensive Cancer Center UCI
  • Florida
    • Pembroke Pines, Florida, United States, 33028
      • Active, not recruiting
      • Memorial Cancer Institute at Memorial West
  • Illinois
    • Chicago, Illinois, United States, 60637
      • Recruiting
      • The University of Chicago
  • Louisiana
    • New Orleans, Louisiana, United States, 70112
      • Active, not recruiting
      • Tulane Medical Center; Investigational/Research Pharmacy
  • Massachusetts
    • Worcester, Massachusetts, United States, 01655
      • Recruiting
      • UMASS Memorial Medical Center
  • New York
    • New York, New York, United States, 10016
      • Recruiting
      • New York University Langone Medical Center
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Active, not recruiting
      • Cleveland Clinic Foundation; Cleveland Clinic Cancer Center/I40
  • Texas
    • Houston, Texas, United States, 77030
      • Recruiting
      • MD Anderson Cancer Center
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Recruiting
      • Medical College of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Life expectancy ≥ 12 weeks
• Histologically confirmed B-cell lymphoma
• One line of prior systemic therapy including an anti-CD20 monoclonal antibody (i.e. rituximab) and an anthracycline
• Relapsed or refractory disease after first-line chemoimmunotherapy
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
• Participant must be a candidate for high-dose chemotherapy followed by ASCT or CAR-T therapy

Exclusion Criteria:

• Treatment with more than one prior line of therapy for DLBCL
• Primary mediastinal B-cell lymphoma
• Prior treatment with glofitamab or other bispecific antibodies targeting both CD20 and CD3
• Peripheral neuropathy assessed to be Grade > 1 according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0 at enrollment
• 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 enrollment or history of CNS lymphoma
• Current or history of CNS disease, such as stroke, epilepsy, CNS vasculitis, or neurodegenerative disease
• Known or suspected history of hemophagocytic lymphohistiocytosis (HLH)
• Known history of progressive multifocal leukoencephalopathy
• Adverse events from prior anti-cancer therapy that have not resolved to Grade 1 or better (with the exception of alopecia and anorexia, or as otherwise permitted by inclusion criteria)
• Prior solid organ transplantation
• Prior allogeneic stem cell transplant
• Prior ASCT for lymphoma
• Prior autologous stem cell transplant for any indication other than lymphoma, within 5 years from the start of study treatment
• Active autoimmune disease requiring treatment
• Prior treatment with systemic immunosuppressive medications (including, but not limited to, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor agents), within 4 weeks prior to first dose of study treatment
• Ongoing corticosteroid use > 30 mg/day of prednisone or equivalent. Participants who received corticosteroid treatment with ≤ 30 mg/day of prednisone or equivalent must be documented to be on a stable dose of at least 4 weeks' duration prior to Cycle 1 Day 1. Participants may have received a brief (≤ 7 days) course of systemic steroids (≤ 100 mg prednisone equivalent per day) prior to initiation of study therapy for control of lymphoma-related symptoms
• Recent major surgery (within 4 weeks before the first study treatment) other than for diagnosis
• Clinically significant history of cirrhotic liver disease

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: R/R DLBCL; Participants will receive up to 3 21-day cycles of glofitamab, rituximab, ifosfamide, carboplatin, and etoposide (glofit-R-ICE).

Drug: Glofitamab; Participants will receive intravenous (IV) glofitamab for up to 3 cycles.; Drug: Obinutuzumab; Participants will receive IV obinutuzumab on Cycle 1 Day 1.; Drug: Tocilizumab; Participants will receive IV tocilizumab as necessary to manage cytokine release syndrome (CRS) events.; Drug: Rituximab; Participants will receive up to 2 doses of IV rituximab.; Drug: Ifosfamide; Participants will receive IV ifosfamide for up to 3 cycles.; Drug: Carboplatin; Participants will receive IV carboplatin for up to 3 cycles.; Drug: Etoposide; Participants will receive IV etoposide for up to 3 cycles.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Objective response rate (ORR), defined as the proportion of participants that achieves a CR or PR within three cycles of glofit-R-ICE, as determined by the investigator according to Lugano criteria	Up to 2.5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of participants with adverse events (AEs)		Up to 2.5 years
Progression-free survival (PFS) after enrollment		From enrollment to the first occurrence of disease progression or death from any cause (whichever occurs first) as determined by the investigator according to Lugano criteria (up to 2.5 years)
Overall survival (OS) after enrollment		From enrollment to death from any cause (up to 2.5 years)
CR rate after enrollment, defined as the proportion of participants that achieves a CR within three cycles of glofit-R-ICE, as determined by the investigator according to Lugano criteria		Up to 2.5 years
Duration of Response (DOR)		From the first occurrence of a documented objective response (CR or PR) to disease progression or death from any cause (whichever occurs first) as determined by the investigator according to Lugano criteria (up to 2.5 years)
Duration of complete response (DOCR)		From the first occurrence of a documented complete response to disease progression or death from any cause (whichever occurs first) as determined by the investigator according to Lugano criteria (up to 2.5 years)
Percentage of participants with cytokine release syndrome (CRS)		Up to 2.5 years
Maximum serum concentration (Cmax) of glofitamab		Up to 2.5 years
Minimum serum concentration (Cmin) of glofitamab		Up to 2.5 years
Percentage of participants with anti-drug antibodies (ADAs)		From baseline up to 2.5 years
Event-free survival (EFS) after enrollment		From enrollment to the first occurrence of disease progression, initiation of new anti-lymphoma therapy (not including planned ASCT or CAR-T therapy), or death from any cause (whichever occurs first) (up to 2.5 years)
Mobilization-adjusted response rate (MARR)	The proportion of participants treated with intent to proceed to ASCT that achieves a CR or PR within three cycles of glofit-R-ICE, as determined by the investigator according to Lugano criteria, and additionally achieves mobilization of a minimum of 2,000,000 CD34+ hematopoietic stem cells/kg for ASCT	Up to 2.5 years

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche
• Investigators: Study Director: Clinical Trials, Hoffmann-La Roche

Study record dates

Study Major Dates

• Study Start (Actual): November 4, 2022
• Primary Completion (Estimated): December 31, 2024
• Study Completion (Estimated): December 31, 2024

Study Registration Dates

• First Submitted: May 3, 2022
• First Submitted That Met QC Criteria: May 3, 2022
• First Posted (Actual): May 6, 2022

Study Record Updates

• Last Update Posted (Actual): April 16, 2024
• Last Update Submitted That Met QC Criteria: April 15, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma; Lymphoma, B-Cell; Lymphoma, Large B-Cell, Diffuse; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antirheumatic Agents; Antineoplastic Agents; Immunologic Factors; Antineoplastic Agents, Alkylating; Alkylating Agents; Antineoplastic Agents, Phytogenic; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Antineoplastic Agents, Immunological; Carboplatin; Etoposide; Ifosfamide; Rituximab; Obinutuzumab
• Other Study ID Numbers: GO43693

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here (https://vivli.org/ourmember/roche/). For further details on Roche's Global Policy on the Sharing of Clinical 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).

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No