glofitamab for Relapsed/refractory B-cell non-Hodgkin lymphoma | Diffuse large B-cell lymphoma | High-grade B-cell lymphoma | Primary mediastinal large B-cell lymphoma | Transformed follicular lymphoma

Inclusion criteria

• {"criterion_text":"- Eastern Cooperative Oncology Group performance status of 0, 1, or 2"}
• {"criterion_text":"- Life expectancy of >= 12 weeks"}
• {"criterion_text":"- Adequate liver function, hematological function, renal function"}
• {"criterion_text":"- Negative serologic and/or polymerase chain reaction test results for acute or chronic hepatitis B virus (HBV) infection"}
• {"criterion_text":"- Negative test results for hepatitis C virus (HCV) and Human immunodeficiency virus (HIV)"}
• {"criterion_text":"- Negative HIV test at screening, with the following exception: - Individuals with a positive HIV test at screening are eligible provided they are stable on antiretroviral therapy for at least 4 weeks, have a CD4 count = 200/mL, have an undetectable viral load, and have not had a history of opportunistic infection attributable to AIDS within the last 12 months - Patients with positive HIV at screening should be monitored while receiving study treatment. HIV viral load will be performed every 3 months (± 4 weeks) in the first 6 months and subsequently every 6 months (± 4 weeks) until end of study treatment. If HIV viral load is detected (positive), the patient should be treated per local institutional standards,and the Medical Monitor should be notified. Testing may be performed at the local institution. If local laboratory assessments are not available for testing, local laboratory collections may be waived only if samples are collected for central laboratory assessments of viral infections"}

Exclusion criteria

• {"criterion_text":"- Patients with chronic lymphocytic leukemia, acute lymphoblastic leukemia (ALL) (including CD20+ ALL), lymphoblastic lymphoma, Richter’s transformation, Burkitt lymphoma or lymphoplasmacytic lymphoma"}
• {"criterion_text":"- Patients with known active infection, or reactivation of a latent infection, whether bacterial, viral, fungal, mycobacterial, or other pathogens or any major episode of infection requiring hospitalization or treatment with IV antibiotics within 4 weeks prior to obinutuzumab (Gazyva, Gazyvaro) pretreatment (Gpt) infusion. Note: Exclusion of patients with mycobacterial infections on the basis of chest X-ray or CT or on the basis of a positive Quantiferon or Mantoux test"}
• {"criterion_text":"- Current Grade > 1 peripheral neuropathy (only for patients being treated in the polatuzumab vedotin arm)"}
• {"criterion_text":"- Patient with history of confirmed progressive multifocal leukoencephalopathy (PML)"}
• {"criterion_text":"- History of leptomeningeal disease, current or past history of central nervous system (CNS) lymphoma and CNS disease, such as stroke, epilepsy, CNS vasculitis, or neurodegenerative disease"}
• {"criterion_text":"- Major surgery or significant traumatic injury <= 28 days prior to Gpt infusion or anticipation of the need for major surgery during study treatment"}

Primary endpoints

• {"endpoint_text":"- 1. Best ORR (CR or PR) based on PET-CT and/or CT scan as determined by the IRC using Lugano 2014 criteria","definition_or_measurement_approach":"Assessed by IRC using PET-CT and/or CT scan according to Lugano 2014 criteria"}
• {"endpoint_text":"- 2. Incidence and nature of dose-limiting toxicities (DLTs) during the DLT observation period","definition_or_measurement_approach":"Recorded during the DLT observation period; incidence and nature of DLTs assessed"}

Secondary endpoints

• {"endpoint_text":"- 1. Best ORR (CR or PR at any time in the study) based on PET-CT and/or CT scan, as determined by the investigator","definition_or_measurement_approach":"Assessed by investigator using PET-CT and/or CT scan"}
• {"endpoint_text":"- 2. Best CR rate on study based on PET-CT and/or CT scan, as determined by the investigator and IRC","definition_or_measurement_approach":"Determined by investigator and IRC using PET-CT and/or CT scan"}
• {"endpoint_text":"- 3. DOCR, defined as the time 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 and IRC","definition_or_measurement_approach":"Time from first documented complete response to disease progression or death, per investigator and IRC"}
• {"endpoint_text":"- 4. DOR, defined as the time from the first occurrence of a documented objective response to disease progression as determined by the investigator and IRC","definition_or_measurement_approach":"Time from first documented objective response to disease progression, per investigator and IRC"}
• {"endpoint_text":"- 5. PFS, defined as the time from first study treatment to the first occurrence of disease progression, or death from any cause, whichever occurs first as determined by the investigator and IRC","definition_or_measurement_approach":"Time from first study treatment to disease progression or death, per investigator and IRC"}
• {"endpoint_text":"- 6. EFS, defined as the time from first study treatment to the first occurrence of disease progression, or relapse initiation of NALT, or death from any cause, whichever occurs first, determined by the investigator and IRC","definition_or_measurement_approach":"Time from first study treatment to progression, relapse/initiation of NALT, or death, per investigator and IRC"}
• {"endpoint_text":"- 7. Time to first complete response (TFCR), defined as time from the start of treatment to the first CR among complete responders, determined by the investigator and IRC","definition_or_measurement_approach":"Time from treatment start to first complete response, per investigator and IRC"}
• {"endpoint_text":"- 8. Time to first overall response (TFOR), defined as the first treatment to first response among responders, determined by the investigator and IRC","definition_or_measurement_approach":"Time from treatment start to first overall response, per investigator and IRC"}
• {"endpoint_text":"- 9. OS, defined as the time from first study treatment to death from any cause","definition_or_measurement_approach":"Time from first study treatment to death from any cause"}
• {"endpoint_text":"- 10. Incidence, nature, frequency, severity, and timing of AEs and serious adverse events (SAEs) graded according to National Cancer Institute Common Terminology Criteria for Adverse Events version 4","definition_or_measurement_approach":"AEs and SAEs graded per NCI CTCAE v4; incidence, nature, frequency, severity, timing recorded"}
• {"endpoint_text":"- 11. Incidence and severity of CRS following glofitamab administration, with severity determined according to ASTCT criteria (Lee et al. 2019; Appendix 6)","definition_or_measurement_approach":"CRS incidence and severity assessed using ASTCT criteria (Lee et al. 2019)"}
• {"endpoint_text":"- 12. Changes in vital signs, electrocardiograms, and clinical laboratory results during and following study treatment administration","definition_or_measurement_approach":"Monitoring of vital signs, ECGs, and clinical laboratory results during and after treatment"}
• {"endpoint_text":"- 13. Incidence of anti-drug antibody formation","definition_or_measurement_approach":"Measurement of anti-drug antibodies (ADA) incidence"}
• {"endpoint_text":"- 14. Elimination half-life","definition_or_measurement_approach":"Pharmacokinetic measurement of elimination half-life"}
• {"endpoint_text":"- 15. Total serum exposure - Area under the concentration-time curve","definition_or_measurement_approach":"AUC measurement of serum exposure"}
• {"endpoint_text":"- 16. Time to maximum observed serum concentration","definition_or_measurement_approach":"PK measurement: time to Cmax"}
• {"endpoint_text":"- 17. Maximum serum concentration observed","definition_or_measurement_approach":"PK measurement: Cmax observed"}
• {"endpoint_text":"- 18. Minimum serum concentration under steady-state conditions within a dosing interval","definition_or_measurement_approach":"PK measurement: trough concentration at steady state"}
• {"endpoint_text":"- 19. Other PK parameters such as clearance (CL), and volume of distribution at steady state (Vss), may also be calculated as data allow.","definition_or_measurement_approach":"PK calculations as data permit (CL, Vss, etc.)"}
• {"endpoint_text":"- 20. CD8-positive T-cell proliferation in tumor tissue and blood","definition_or_measurement_approach":"Biomarker assessment of CD8+ T-cell proliferation in tumor tissue and blood"}
• {"endpoint_text":"- 21. B-cell reduction in blood and tumor tissue","definition_or_measurement_approach":"Biomarker assessment of B-cell reduction in blood and tumor tissue"}

Denmark

Earliest CTIS Part Ii Submission Date

27-02-2024

Latest Decision Or Authorization Date

06-03-2026

Processing Time Days

739

Number Of Sites

3

Number Of Participants

42

Belgium

Earliest CTIS Part Ii Submission Date

27-02-2024

Latest Decision Or Authorization Date

09-03-2026

Processing Time Days

742

Number Of Sites

1

Number Of Participants

15

Italy

Earliest CTIS Part Ii Submission Date

27-02-2024

Latest Decision Or Authorization Date

20-03-2026

Processing Time Days

753

Number Of Sites

4

Number Of Participants

52

Spain

Earliest CTIS Part Ii Submission Date

27-02-2024

Latest Decision Or Authorization Date

31-03-2026

Processing Time Days

764

Number Of Sites

5

Number Of Participants

64

Primary sponsor

Full Name

F. Hoffmann-La Roche AG

Organisation Type

Pharmaceutical company

Country Of Registered Address

Switzerland

Contract research organisations

Name

Icon Development Solutions LLC

Responsibilities

code: 4

Name

IQVIA Limited

Responsibilities

Site management provider

Name

PPD Development LP

Responsibilities

code: 4

Name

QPS Netherlands B.V.

Responsibilities

code: 4

Name

Endpoint Clinical Inc.

Responsibilities

IxRS Provider

Third parties

• {"country":"United States","full_name":"Icon Development Solutions LLC","duties_or_roles":"code: 4","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Q Squared Solutions Holdings LLC","duties_or_roles":"code: 4","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"Germany","full_name":"MicroCoat Biotechnologie GmbH","duties_or_roles":"code: 4","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"IQVIA Limited","duties_or_roles":"Site management provider (code: 15)","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Imaging Endpoints II LLC","duties_or_roles":"code: 4","organisation_type":"Pharmaceutical company"}
• {"country":"Belgium","full_name":"CellCarta","duties_or_roles":"code: 4","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"Germany","full_name":"Discovery Life Sciences Biomarker Services GmbH","duties_or_roles":"code: 4","organisation_type":"Pharmaceutical company"}
• {"country":"France","full_name":"Median Technologies","duties_or_roles":"code: 4","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"Q Squared Solutions Limited","duties_or_roles":"code: 4","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"Iqvia Laboratories Limited","duties_or_roles":"code: 4","organisation_type":"Non-Pharmaceutical company"}
• {"country":"Netherlands","full_name":"QPS Netherlands B.V.","duties_or_roles":"code: 4","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"PPD Development LP","duties_or_roles":"code: 4","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Endpoint Clinical Inc.","duties_or_roles":"IxRS Provider (code: 15)","organisation_type":"Pharmaceutical company"}