Clinical Trials /

An Open-Label Phase lB Study of RO7082859 and Atezolizumab in Adult Patients With Relapsed/Refractory B-Cell Non-Hodgkin's Lymphoma

NCT03533283

Description:

This is an open-label, single arm, multicenter, dose finding, Phase Ib study in order to assess the maximum tolerated dose (MTD) and/or recommended Phase II dose (RP2D) for this combination treatment and to evaluate the general safety, tolerability, pharmacokinetic (PK), pharmacodynamic, and preliminary anti-tumor activity of this combination treatment in adult patients.

Related Conditions:
  • B-Cell Non-Hodgkin Lymphoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: An Open-Label Phase lB Study of RO7082859 and Atezolizumab in Adult Patients With Relapsed/Refractory B-Cell Non-Hodgkin's Lymphoma
  • Official Title: An Open-Label, Multi-Center, Phase IB Study of RO7082859 and Atezolizumab (Plus a Single Pre-Treatment Dose of Obinutuzumab) in Adult Patients With Relapsed/Refractory B-Cell Non-Hodgkin's Lymphoma

Clinical Trial IDs

  • ORG STUDY ID: NP39488
  • NCT ID: NCT03533283

Conditions

  • Non-Hodgkins Lymphoma

Interventions

DrugSynonymsArms
RO7082859Dose Escalation and Expansion
AtezolizumabDose Escalation and Expansion
ObinutuzumabDose Escalation and Expansion

Purpose

This is an open-label, single arm, multicenter, dose finding, Phase Ib study in order to assess the maximum tolerated dose (MTD) and/or recommended Phase II dose (RP2D) for this combination treatment and to evaluate the general safety, tolerability, pharmacokinetic (PK), pharmacodynamic, and preliminary anti-tumor activity of this combination treatment in adult patients.

Trial Arms

NameTypeDescriptionInterventions
Dose Escalation and ExpansionExperimentalParticipants will receive RO7082859 in combination with Atezolizumab up to the maximum tolerated dose (MTD).
  • RO7082859
  • Atezolizumab
  • Obinutuzumab

Eligibility Criteria

        Main Inclusion Criteria

          -  Histologically-confirmed hematologic malignancy that is expected to express CD20
             (Relapsed after or failed to respond to at least one prior treatment regiment; no
             available treatment options that are expected to prolong survival or patients refusing
             chemotherapy or autologous stem cell transplant (SCT). Note: The expansion part is
             restricted to relapsed/refractory follicular lymphoma (r/r FL) and relapsed/refractory
             diffuse large B cell lymphoma (r/r DLBCL))

          -  At least one measurable target lesion

          -  Fresh pre-treatment biopsy, but if this cannot be taken, a previous archived biopsy
             from metastatic lesion can be taken as replacement if it is not older than 6 months
             and not confounded by major events (progression, treatment)

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

          -  Adequate organ function (liver, hematological, renal)

          -  Negative test results for hepatitis B virus (HBV), hepatitis C virus (HCV), and human
             immunodeficiency virus (HIV)

        Main Exclusion Criteria

          -  Patients with Chronic Lymphocytic Leukemia (CLL), CD20-positive Acute Lymphoblastic
             Leukemia (ALL), Burkitt lymphoma, or lymphoplasmacytic lymphoma

          -  Patients with known active infection, or reactivation of a latent infection within 4
             weeks prior to Obinutuzumab (Gpt) infusion

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

          -  History of leptomeningeal disease

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

          -  Current or past history of CNS disease

          -  Major surgery or significant traumatic injury </=28 days prior to Gpt infusion

          -  Significant cardiovascular disease or significant pulmonary disease

          -  Active or history of autoimmune disease or immune deficiency (with exceptions, e.g.
             hypothyroidism and Diabetes mellitus Type 1)

          -  History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g. bronchiolitis
             obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of
             active pneumonitis on screening chest computed tomography (CT) scan

          -  Treatment with any other standard anti-cancer radiotherapy / chemotherapy including
             investigational therapy within 4 weeks prior to Gpt infusion

          -  Prior solid organ transplantation

          -  Prior allogenic stem cell transplant (SCT)

          -  Autologous SCT within 100 days prior to Gpt infusion

          -  Documented refractoriness to an obinutuzumab-monotherapy regimen

          -  Prior treatment with targeted therapies and systemic
             immunotherapeutic/immunostimulating agents within 4 weeks or 5 half-lives of the drug,
             whichever is shorter, prior to Gpt infusion

          -  Any history of immune related >/= Grade 3 adverse events (AE) with the exception of
             endocrinopathy managed with replacement therapy

          -  Ongoing corticosteroid use >25 milligrams/day of prednisone or equivalent within 4
             weeks prior to and during study treatment

          -  Treatment with systemic immunosuppressive medication

          -  Administration of a live, attenuated vaccine within 4 weeks prior to Gpt infusion or
             anticipation that such a live attenuated vaccine will be required during the study or
             within 5 months after last dose of study treatment
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Dose Limiting Toxicities (DLTs)
Time Frame:During DLT period of 21 days (or up to 42 days in the case of cycle delay), starting on Day 1 of Cycle 2
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Percentage of Participants with Adverse Events (AEs)
Time Frame:Baseline until end of treatment (13 to 14 months), then every 3 months until end of study visit (to occur within 4 weeks of disease progression)
Safety Issue:
Description:
Measure:Anti-Drug Antibody (ADA) Formation
Time Frame:Baseline until end of treatment (13 to 14 months), then every 3 months until end of study visit (to occur within 4 weeks of disease progression)
Safety Issue:
Description:
Measure:Complete Response (CR) Rate, as Assessed by Fluorodeoxyglucose-Positron Emission Tomography/Computed Tomography (FDG-PET/CT) Scan
Time Frame:Baseline until end of treatment (13 to 14 months), then every 3 months until end of study visit (to occur within 4 weeks of disease progression)
Safety Issue:
Description:
Measure:Objective Response Rate (ORR)
Time Frame:Baseline until end of treatment (13 to 14 months), then every 3 months until end of study visit (to occur within 4 weeks of disease progression)
Safety Issue:
Description:
Measure:Disease Control Rate (DCR)
Time Frame:Baseline until end of treatment (13 to 14 months), then every 3 months until end of study visit (to occur within 4 weeks of disease progression)
Safety Issue:
Description:
Measure:Duration of Response (DOR)
Time Frame:Baseline until end of treatment (13 to 14 months), then every 3 months until end of study visit (to occur within 4 weeks of disease progression)
Safety Issue:
Description:
Measure:Progression-Free Survival (PFS)
Time Frame:Baseline until end of treatment (13 to 14 months), then every 3 months until end of study visit (to occur within 4 weeks of disease progression)
Safety Issue:
Description:
Measure:Overall Survival (OS)
Time Frame:Baseline through end of survival follow-up phase (survival follow-up is every 3 months until death, lost to follow-up, withdrawal of consent, or study termination)
Safety Issue:
Description:
Measure:Elimination Half-Life (T1/2) of RO7082859 Administered in Combination with Atezolizumab
Time Frame:At pre-defined intervals through the end of study (EoS) visit (to occur within 4 weeks of disease progression)
Safety Issue:
Description:
Measure:Area Under the Concentration-Time Curve (AUC) for RO7082859 Administered in Combination with Atezolizumab
Time Frame:At pre-defined intervals through the end of study (EoS) visit (to occur within 4 weeks of disease progression)
Safety Issue:
Description:
Measure:Time to Maximum Observed Serum Concentration (Tmax) of RO7082859 Administered in Combination with Atezolizumab
Time Frame:At pre-defined intervals through the end of study (EoS) visit (to occur within 4 weeks of disease progression)
Safety Issue:
Description:
Measure:Maximum Observed Serum Concentration (Cmax) of RO7082859 Administered in Combination with Atezolizumab
Time Frame:At pre-defined intervals through the end of study (EoS) visit (to occur within 4 weeks of disease progression)
Safety Issue:
Description:
Measure:Minimum Serum Concentration (Cmin) of RO7082859 Administered in Combination with Atezolizumab
Time Frame:At pre-defined intervals through the end of study (EoS) visit (to occur within 4 weeks of disease progression)
Safety Issue:
Description:
Measure:Clearance (CL) of RO7082859 Administered in Combination with Atezolizumab
Time Frame:At pre-defined intervals through the end of study (EoS) visit (to occur within 4 weeks of disease progression)
Safety Issue:
Description:
Measure:Volume of Distribution at Steady-State (Vss) of RO7082859 Administered in Combination with Atezolizumab
Time Frame:At pre-defined intervals through the end of study (EoS) visit (to occur within 4 weeks of disease progression)
Safety Issue:
Description:
Measure:CD8-Positive T Cell Proliferation
Time Frame:At pre-defined intervals during the study treatment period (up to 17 cycles; Cycle = 21 days)
Safety Issue:
Description:
Measure:CD20-Positive B-Cell Reduction
Time Frame:At pre-defined intervals during the study treatment period (up to 17 cycles; Cycle = 21 days)
Safety Issue:
Description:

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Hoffmann-La Roche

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