A Study to Evaluate Glofitamab as Single Agent Administered After Pretreatment With Obinutuzumab in Chinese Patients With Relapsed/Refractory Diffuse Large B-Cell Lymphoma

NCT04657302 | Completed Phase 1

• 1 other identifier: YO42610
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 6

Brief Summary

This study will evaluate the pharmacokinetics, safety, tolerability, and efficacy of glofitamab as a single agent following a fixed single dose of obinutuzumab in Chinese patients with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL) who have failed two or more lines of systemic therapy.

Conditions

Lymphoma

Outcome Measures

Primary Outcomes (10)

• Percentage of Participants with Adverse Events (AEs)

  Up to 3.5 years

• Serum Concentration of Glofitamab

  At pre-defined intervals up to 3.5 years

• Total Exposure (AUC) of Glofitamab

  At pre-defined intervals up to 3.5 years

• Maximum Serum Concentration (Cmax) of Glofitamab

  At pre-defined intervals up to 3.5 years

• Minimum Serum Concentration (Cmin) of Glofitamab

  At pre-defined intervals up to 3.5 years

• Clearance of Glofitamab

  At pre-defined intervals up to 3.5 years

• Volume of Distribution at Steady State (Vss) of Glofitamab

  At pre-defined intervals up to 3.5 years

• Half-life (T1/2) of Glofitamab

  At pre-defined intervals up to 3.5 years

• Complete Response Rate (CRR) as Assessed by an Independent Review Committee (IRC)

  Up to 3.5 years

• Percentage of Participants with Anti-Drug Antibodies (ADA)

  Up to 3.5 years

Secondary Outcomes (9)

• Investigator-Assessed CRR

  Up to 3.5 years

• Objective Response Rate (ORR) as Assessed by IRC

  Up to 3.5 years

• ORR as Assessed by Investigator

  Up to 3.5 years

• Duration of Objective Response (DOR) as Assessed by IRC and Investigator

  Up to 3.5 years

• Duration of Complete Response (CR) as Assessed by IRC and Investigator

  Up to 3.5 years

Study Arms (1)

R/R DLBCL

EXPERIMENTAL

Participants will receive a fixed dose of obinutuzumab pre-treatment followed by glofitamab on Cycle 1 Days 8 and 15, then every 3 weeks (Q3W) from Cycles 2-12 (cycle length = 21 days).

Drug: Obinutuzumab; Drug: Glofitamab; Drug: Tocilizumab

Interventions

Obinutuzumab DRUG

Participants will receive 1000 mg of intravenous (IV) obinutuzumab on Cycle 1 Day 1.

R/R DLBCL

Glofitamab DRUG

Participants will receive 2.5 mg of IV glofitamab Cycle 1 Day 8, 10 mg at Cycle 1 Day 15, and 30 mg on Day 1 of Cycles 2-12 Q3W (cycle length = 21 days).

R/R DLBCL

Tocilizumab DRUG

Participants will receive tocilizumab as needed to manage cytokine release syndrome (CRS).

R/R DLBCL

Eligibility Criteria

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

You may qualify if:

• Histologically-confirmed DLBCL
• Participants must have relapsed or failed to respond to at least two lines of prior systemic therapy (including at least one prior regimen containing anthracycline, and at least one containing an anti-CD20-directed therapy)
• Participants must have measurable disease: at least one bi-dimensionally measurable nodal lesion, defined as \> 1.5 cm in its longest dimension; or at least one bi-dimensionally measurable extranodal lesion, defined as \> 1.0 cm in its longest dimension
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 1 or 1
• Adverse events from prior anti-cancer therapy must have resolved to Grade \</=1
• Adequate liver, hematological, and renal function
• Negative serum pregnancy test within 7 days prior to study treatment in women of childbearing potential
• Women of childbearing potential must agree to remain abstinent (refrain from heterosexual intercourse) or use contraception as defined by the protocol, and agree to refrain from donating eggs during the treatment period and for at least 18 months after the final dose of obinutuzumab, 2 months after the final dose of glofitamab, and 3 months after the final dose of tocilizumab (if applicable)
• Men must agree to remain abstinent (refrain from heterosexual intercourse) or use contraception as defined by the protocol, and agree to refrain from donating sperm during the treatment period and for at least 3 months after the final dose of obinutuzumab, 4 months after the final dose of glofitamab, and 2 months after the final dose of tocilizumab (if applicable)
• Reside in the People's Republic of China

You may not qualify if:

• Richter's transformation
• Known active bacterial, viral, fungal, mycobacterial, parasitic, or other infection (excluding fungal infections of nail beds) at study enrollment or any major episode of infection within 4 weeks prior to first study treatment
• Suspected or latent tuberculosis
• Positive for HIV, hepatitis C (HCV), or hepatitis B (HBV)
• Known or suspected chronic active Epstein-Barr virus infection
• Known or suspected history of hemaphagocytic lymphohistiocytosis (HLH)
• Prior treatment with systemic immunotherapeutic agents
• History of treatment-emergent immune-related adverse events associated with prior immunotherapeutic agents
• Documented refractoriness to an obinutuzumab monotherapy-containing regimen
• Treatment with standard radiotherapy, any chemotherapeutic agent, including CAR T therapy
• Prior solid organ or allogenic stem cell transplantation
• Autologous stem cell transplantation within 100 days prior to obinutuzumab infusion
• Active autoimmune disease requiring treatment
• History of severe allergic or anaphylactic reactions to monoclonal antibody therapy (or recombinant antibody-related fusion proteins)
• History of confirmed progressive multifocal leukoencephalopathy (PML)

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (6)

Beijing Cancer Hospital

Beijing, 100142, China

Location

Peking University Third Hospital

Beijing, 100191, China

Location

Cancer Center, Sun Yat-sen University of Medical Sciences; Department of Medical Oncology

Guangzhou, 510060, China

Location

Harbin Medical University Cancer Hospital

Harbin, 150081, China

Location

Jiangsu Province Hospital

Nanjing, 210008, China

Location

Tianjin Cancer Hospital

Tianjin, 300060, China

Location

MeSH Terms

Conditions

Lymphoma

Interventions

obinutuzumab; glofitamab; tocilizumab

Condition Hierarchy (Ancestors)

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: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 1, 2020
• First Posted: December 8, 2020
• Study Start: January 8, 2021
• Primary Completion: October 25, 2022
• Study Completion: January 12, 2024
• Last Updated: January 19, 2024

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will share

Locations

CN (6)