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

Lymphoma Clinical Trial

Official title:

A Phase I, Open-Label, Multicenter Study to Evaluate the Pharmacokinetics, Safety, Tolerability, and Efficacy of Glofitamab as Single Agent Administered After a Fixed, Single Dose Pretreatment of Obinutuzumab in Chinese Patients With Relapsed/Refractory Diffuse Large B-Cell Lymphoma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04657302
• Other study ID #: YO42610
• Status: Completed
• Phase: Phase 1
• Start date: January 8, 2021
• Est. completion date: January 12, 2024

Study information

• Verified date: January 2024
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 30
• Est. completion date: January 12, 2024
• Est. primary completion date: October 25, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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)

• Current or past history of CNS lymphoma

• Current or past history of central nervous system (CNS) disease, such as stroke, epilepsy, CNS vasculitis, or neurodegenerative disease

• Evidence of significant, uncontrolled concomitant diseases that could affect compliance with the protocol or interpretation of results, including diabetes mellitus, history of relevant pulmonary disorders, and known autoimmune diseases

• Major surgery or significant traumatic injury < 28 days prior to obinutuzumab infusion (excluding biopsies) or anticipation of the need for major surgery during study treatment

• Another invasive malignancy in the last 2 years

• Significant cardiovascular disease

• Administration of a live, attenuated vaccine within 4 weeks before obinutizumab infusion, or anticipation that one will be required during the study

• Systemic immunosuppresive medications

Related Conditions & MeSH terms

• Lymphoma
• Lymphoma, Large B-Cell, Diffuse

Intervention

Drug:
• Obinutuzumab
Participants will receive 1000 mg of intravenous (IV) obinutuzumab on Cycle 1 Day 1.
• Glofitamab
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).
• Tocilizumab
Participants will receive tocilizumab as needed to manage cytokine release syndrome (CRS).

Locations

Country	Name	City	State
China	Beijing Cancer Hospital	Beijing
China	Peking University Third Hospital	Beijing
China	Cancer Center, Sun Yat-sen University of Medical Sciences; Department of Medical Oncology	Guangzhou City
China	Harbin Medical University Cancer Hospital	Harbin
China	Jiangsu Province Hospital	Nanjing
China	Tianjin Cancer Hospital	Tianjin

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants with Adverse Events (AEs)		Up to 3.5 years
Primary	Serum Concentration of Glofitamab		At pre-defined intervals up to 3.5 years
Primary	Total Exposure (AUC) of Glofitamab		At pre-defined intervals up to 3.5 years
Primary	Maximum Serum Concentration (Cmax) of Glofitamab		At pre-defined intervals up to 3.5 years
Primary	Minimum Serum Concentration (Cmin) of Glofitamab		At pre-defined intervals up to 3.5 years
Primary	Clearance of Glofitamab		At pre-defined intervals up to 3.5 years
Primary	Volume of Distribution at Steady State (Vss) of Glofitamab		At pre-defined intervals up to 3.5 years
Primary	Half-life (T1/2) of Glofitamab		At pre-defined intervals up to 3.5 years
Primary	Complete Response Rate (CRR) as Assessed by an Independent Review Committee (IRC)		Up to 3.5 years
Primary	Percentage of Participants with Anti-Drug Antibodies (ADA)		Up to 3.5 years
Secondary	Investigator-Assessed CRR		Up to 3.5 years
Secondary	Objective Response Rate (ORR) as Assessed by IRC		Up to 3.5 years
Secondary	ORR as Assessed by Investigator		Up to 3.5 years
Secondary	Duration of Objective Response (DOR) as Assessed by IRC and Investigator		Up to 3.5 years
Secondary	Duration of Complete Response (CR) as Assessed by IRC and Investigator		Up to 3.5 years
Secondary	Progression-Free Survival (PFS) as Determined by IRC and Investigator		Up to 3.5 years
Secondary	Overall Survival (OS)		Up to 3.5 years
Secondary	Time to First Overall Response (TFOR) as Assessed by IRC and Investigator		Up to 3.5 years
Secondary	Time to First Complete Response (TFCR) as Assessed by IRC and Investigator		Up to 3.5 years