Informations générales (source: ClinicalTrials.gov)
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
Interventional
Phase 1/Phase 2
Hoffmann-La Roche (Voir sur ClinicalTrials)
février 2017
août 2027
15 juillet 2025
This is a Phase I/II, multicenter, open-label, dose-escalation study designed to evaluate
the efficacy, safety, tolerability and pharmacokinetics (PK) of a novel T-Cell bispecific
(TCB), glofitamab, administered by intravenous (IV) infusion as a single agent and in
combination with obinutuzumab, following pre-treatment with a one-time, fixed dose of
obinutuzumab. This entry-into-human (EIH) study is divided in 3 parts: dose escalation
(Parts I and II) and dose expansion (Part III). Single-participant dose-escalation
cohorts will be used in Part I, followed by conversion to multiple participant
dose-escalation cohorts (Part II), in order to define a tentative maximum tolerated dose
(MTD) or optimal biological dose (OBD). The expansion cohorts (Part III) will be
initiated when the tentative MTD/OBD is defined, to further evaluate the safety, PK and
therapeutic activity of glofitamab.
Etablissements
| Les établissements d'Île-de-France dont les données sont issues de ClinicalTrials.gov Origine et niveau de fiabilité des données | |||||
|---|---|---|---|---|---|
| AP-HP - Hôpital Henri Mondor-Albert Chenevier | Contact (sur clinicalTrials) | ||||
| Les établissements sans correspondance certaine dans le répertoire FINESS dont les données sont issues de ClinicalTrials.gov Origine et niveau de fiabilité des données | |||||
| Ch Lyon Sud - 69495 - Pierre Benite - France | Contact (sur clinicalTrials) | ||||
| CHU DE RENNES - CHU Pontchaillou - 35033 - Rennes - France | Contact (sur clinicalTrials) | ||||
| CHU Saint Eloi - 34295 - Montpellier - France | Contact (sur clinicalTrials) | ||||
| Hopital Claude Huriez - 59037 - Lille - France | Contact (sur clinicalTrials) | ||||
Critères
Tous
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 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
- Able to provide a tumor tissue pretreatment biopsy at last relapse or during
screening 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
(</=) 1
- 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
- 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 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
- Able to provide a tumor tissue pretreatment biopsy at last relapse or during
screening 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
(</=) 1
- 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
- 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 stem cell transplantation (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 </= 25 mg/day prednisone or equivalent is allowed. Inhaled and
topical 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 diffuse large B-cell lymphoma (DLBCL) dexamethasone cohort, participants
with a history of hypersensitivity to dexamethasone or systemic corticosteroids will
be excluded