SHS_492452 PATK CROC 18226

A Multicenter, Open-Label, Phase I Study to Evaluate the Safety, Tolerability and Pharmacokinetics of Escalating Doses of RO7082859 as a Single Agent and in Combination With Obinutuzumab, Administered After a Fixed, Single Pre-Treatment Dose of Obinutuzumab (Gazyva®/Gazyvaro™) in Patients With Relapsed/Refractory B-Cell Non-Hodgkin's Lymphoma

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 [SCT])
Participant must have at least one measureable target lesion (>/=1.5 centimeters [cm]) in its largest dimension by computerized tomography [CT] scan)
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)
Exclusion Criteria:

Participants with chronic lymphocytic leukemia (CLL), Burkitt lymphoma and lymphoplasmacytic lymphoma
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 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
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)
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) with the exception of corticosteroid treatment 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
Phase I
Krish Patel, M.D.
Roche Holding AG (Hoffman-LaRoche)
Ngan Trinh
  • Swedish Medical Center