A Dose Escalation Study of Glofitamab (RO7082859) as a Single Agent and in Combination With Obinutuzumab, Administered After a Fixed, Single Pre-Treatment Dose of Obinutuzumab in Participants With Relapsed/Refractory B-Cell Non-Hodgkin's Lymphoma

• Register: ClinicalTrials.gov
• Last refreshed on: 22 April 2024
• Main ID: NCT03075696
• Date of registration: 07/03/2017
• Prospective Registration: No
• Primary sponsor: Hoffmann-La Roche
• Public title: A Dose Escalation Study of Glofitamab (RO7082859) as a Single Agent and in Combination With Obinutuzumab, Administered After a Fixed, Single Pre-Treatment Dose of Obinutuzumab in Participants With Relapsed/Refractory B-Cell Non-Hodgkin's Lymphoma
• Scientific title: A Multicenter, Open-Label, Phase I/II Study to Evaluate the Safety, Efficacy, Tolerability and Pharmacokinetics of Escalating Doses of Glofitamab (RO7082859) as a Single Agent and in Combination With Obinutuzumab Administered After a Fixed, Single Dose Pre-Treatment of Obinutuzumab (Gazyva®/Gazyvaro™) in Patients With Relapsed/Refractory B-Cell Non-Hodgkin's Lymphoma
• Date of first enrolment: February 21, 2017
• Target sample size: 860
• Recruitment status: Recruiting
• URL: https://clinicaltrials.gov/ct2/show/NCT03075696
• Study type: Interventional
• Study design: Allocation: Non-Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 1/Phase 2

Countries of recruitment

Australia, Belgium, Canada, Czechia, Denmark, Finland, France, Italy, New Zealand, Poland, Spain, Taiwan, United States

Contacts

• Name: Clinical Trials
• Affiliation: Hoffmann-La Roche

• Name: Reference Study ID Number: NP30179 https://forpatients.roche.com/

Key inclusion & exclusion criteria

Inclusion Criteria:

- Depending upon study part, a history or status of: 1) a histologically-confirmed
hematological malignancy that is expected to express cluster of differentiation
(CD)20; 2) relapse after or failure to respond to at least one prior treatment
regimen; and 3) no available treatment options that are expected to prolong survival
(e.g., standard chemotherapy or autologous stem cell transplant [ASCT])

- Measurable disease, defined as at lease one bi-dimensionally measurable nodal lesion,
defined as > 1.5 cm in its longest dimension, or at least one bi-dimensionally
measureable extranodal lesion, defined as > 1.0 cm in its longest dimension

- Able to provide a fresh biopsy from a safely accessible site, per investigator
determination, providing the patient has more than one measurable target lesion

- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

- Life expectancy of >/=12 weeks

- AEs from prior anti-cancer therapy must have resolved to Grade less than or equal to
(
- Adequate liver, hematological and renal function

- Negative serologic or polymerase chain reaction (PCR) test results for acute or
chronic Hepatitis B virus (HBV) infection

- Negative test results for Hepatitis C virus (HCV) and human immunodeficiency virus
(HIV)

- Negative serum pregnancy test within 7 days prior to study treatment in women of
childbearing potential. Women who are not of childbearing potential who are considered
to be post-menopausal (at least 12 months of non-therapy amenorrhea) or surgically
sterile (absence of ovaries and/or uterus) are not required to have a pregnancy test

Exclusion Criteria:

- Inability to comply with protocol mandated hospitalizations and restrictions

- Participants with chronic lymphocytic leukemia (CLL), Burkitt lymphoma and
lymphoplasmacytic lymphoma

- Participants with a known or suspected history of hemophagocytic lymphohistiocytosis
(HLH)

- Participants with acute bacterial, viral, or fungal infection at baseline, confirmed
by a positive blood culture within 72 hours prior to obinutuzumab infusion or by
clinical judgment in the absence of a positive blood culture

- Participants 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 of dosing

- Prior treatment with systemic immunotherapeutic agents, including, but not limited to,
radio-immunoconjugates, antibody-drug conjugates, immune/cytokines and monoclonal
antibodies (e.g., anti-cytotoxic T-lymphocyte-associated protein 4 [anti-CTLA4],
anti-programmed death 1 [anti-PD1] and anti-programmed death ligand 1 [anti-PDL1])
within 4 weeks or five half-lives of the drug, whichever is shorter, before
obinutuzumab infusion on Cycle 1 Day -7

- History of treatment-emergent immune-related AEs associated with prior
immunotherapeutic agents

- Documented refractoriness to an obinutuzumab-containing regimen

- Treatment with standard radiotherapy, any chemotherapeutic agent, or treatment with
any other investigational anti-cancer agent, including chimeric antigen receptor
therapy (CAR-T) within 4 weeks prior to obinutuzumab infusion

- Prior solid organ transplantation

- Prior allogeneic SCT

- Autologous SCT within 100 days prior to obinutuzumab infusion

- Participant with history of confirmed progressive multifocal leukoencephalopathy (PML)

- Current or past history of central nervous system (CNS) lymphoma

- Current or past history of CNS disease, such as stroke, epilepsy, CNS vasculitis, or
neurodegenerative disease. Participants with a past history of stroke that have not
experienced a stroke or transient ischemic attack in the past 2 years and have no
residual neurologic deficits are allowed.

- 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

- Participants with another invasive malignancy in the last 2 years (with the exception
of basal cell carcinoma and tumors deemed by the Investigator to be of low likelihood
for recurrence)

- Significant or extensive history of cardiovascular disease such as New York Heart
Association Class III or IV or Objective Class C or D cardiac disease, myocardial
infarction within the last 6 months, unstable arrhythmias, or unstable angina

- Administration of a live, attenuated vaccine within 4 weeks before obinutuzumab
infusion or anticipation that such a live attenuated vaccine will be required during
the study

- Received systemic immunosuppressive medications (including but not limited to
cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis
factor agents) within two weeks prior to obinutuzumab infusion. Treatment with
corticosteroid steroids are permitted.

- Any other diseases, metabolic dysfunction, physical examination finding, or clinical
laboratory finding giving reasonable suspicion of a disease or condition that would
contraindicate the use of an investigational drug

- History of autoimmune disease, including but not limited to myocarditis, pneumonitis,
myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus, erythematosus,
rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with
antiphospholipid syndrome, Wegener's granulomatosis, Sjögren's syndrome,
Guillain-Barré syndrome, multiple sclerosis, vasculitis, or glomerulonephritis.
Participants with a remote history of, or well controlled autoimmune disease, may be
eligible to enroll after consultation with the Medical Monitor

- In Part III DLBCL dexamethasone cohort, patients with a history of hypersensitivity to
dexamethasone or systemic corticosteroids will be excluded



Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Non-Hodgkin's Lymphoma

Intervention(s)

Drug: Glofitamab

Drug: Obinutuzumab

Drug: Tocilizumab

Primary Outcome(s)

Part I, II and III: Clearance (CL) of Glofitamab [Time Frame: At pre-defined intervals from Cycle 1 Day 1 to Day 71]

Part III: Complete Response (CR) Rate as Assessed by Independent Review Committee (IRC) According to Standard Non-Hodgkin's Lymphoma (NHL) Response Criteria (Lugano Classification) [Time Frame: From treatment start up to 5 years]

Part I, II and III: Half-Life (t1/2) of Glofitamab [Time Frame: At pre-defined intervals from Cycle 1 Day 1 to Day 71]

Part I, II and III: Percentage of Participants With Adverse Events (AEs) [Time Frame: From Baseline up to 90 days after last dose of study drug or until study completion or participant withdrawal (up to 5 years)]

Part I, II and III: Volume of Distribution at Steady-State (Vss) of Glofitamab [Time Frame: At pre-defined intervals from Cycle 1 Day 1 to Day 71]

Part I and II: Percentage of Participants With Dose Limiting Toxicities (DLTs) [Time Frame: From Baseline up to 4 weeks]

Part I, II and III: Minimum Serum Concentration (Cmin) of Glofitamab [Time Frame: At pre-defined intervals from Cycle 1 Day 1 up to Day 198]

Part II: Recommended Phase II Dose (RP2D) of Glofitamab [Time Frame: From Baseline up to 5 years]

Part I, II and III: Area Under the Serum Concentration Versus Time Curve (AUC) of Glofitamab [Time Frame: At pre-defined intervals from Cycle 1 Day 1 to Day 71]

Part I, II and III: Maximum Serum Concentration (Cmax) of Glofitamab [Time Frame: At pre-defined intervals from Cycle 1 Day 1 to Day 198]

Part II: MTD or OBD of Glofitamab [Time Frame: From Baseline up to 4 weeks]

Secondary Outcome(s)

Part I, II and III: Progression-Free Survival (PFS) as Determined by the Lugano Classification [Time Frame: From first study treatment to the first occurrence of disease progression or death due to any cause (up to 5 years)]

Parts I and II: Percentage of Participants With Overall Response (Partial Response [PR] or Complete Response [CR]) as Determined by the Lugano Classification [Time Frame: From Baseline up to end of study or discontinuation due to disease progression (up to 5 years)]

Time to First Overall Response (TFOR) [Time Frame: From time of treatment start to first documented response (up to 5 years)]

Part I, II and III: Anti-Drug Antibodies (ADA) to Glofitamab [Time Frame: Pre-dose of obinutuzumab on Day -7; pre-dose (Hr 0) of glofitamab on Day 1 of each cycle from Cycle 2 onwards for a maximum of 8-12 cycles, and at EOT/follow-up visit (up to 5 years)]

Overall Survival (OS) [Time Frame: From the time of first study treatment to death from any cause (up to 5 years)]

Health Related Quality of Life (HRQoL) as Assessed by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) [Time Frame: From baseline through follow-up or until disease progression (up to 5 years)]

HRQoL as Assessed by the Functional Assessment of Cancer Therapy-Lymphoma (FACT-Lym) Lymphoma Scale [Time Frame: From baseline through follow-up or until disease progression (up to 5 years)]

Part I, II and III: Cmax of Obinutuzumab [Time Frame: Pre-dose of obinutuzumab on Day -7; pre-dose (Hr 0) of glofitamab on Day 1 of Cycle 1]

Part I, II and III: Percentage of Participants With PR or CR (Overall Response Rate) as Determined by the Lugano Classifications [Time Frame: From Baseline up to end of study or discontinuation due to disease progression (up to 5 years)]

Part I, II and III: Cmin of Obinutuzumab [Time Frame: Pre-dose of obinutuzumab on Day -7; pre-dose (Hr 0) of glofitamab on Day 1 of Cycle 1]

Time to First Complete Response (TFCR) [Time Frame: From treatment start to first documented complete response (up to 5 years)]

Part I, II and III: Duration of Complete Response (DOCR) as Determined by the Lugano Classification [Time Frame: From the first occurrence of a documented, complete response, until the time of relapse or death from any cause (up to 5 years)]

Part I, II and III: Duration of Response (DOR) as Determined by the Lugano Classification [Time Frame: From first occurrence of documented objective response until disease progression, relapse or death due to any cause (up to 5 years)]

Secondary ID(s)

2016-001185-28

NP30179

Source(s) of Monetary Support

Please refer to primary and secondary sponsors