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

Sponsor
Hoffmann-La Roche
Study ID
NCT03533283
Phase
PHASE1/PHASE2
Status
Active Not Recruiting

Conditions

  • Non-Hodgkins Lymphoma

Eligibility Criteria

Sex
ALL
Age
18 Years - N/A
Healthy Volunteers
Not accepted

Interventions

  • Glofitamab — DRUG
    Glofitamab will be administered through IV infusion every 3 weeks (Q3W) beginning Cycle 1, Day 1, for up to 17 cycles (Cycle = 21 days). Step-up dosing, in which an initial lower dose will be followed by a higher dose 1 week later, will be considered for the initial treatment phase and for Cycle 9 of the re-treatment phase.
  • Atezolizumab — DRUG
    Atezolizumab will be administered in combination with Glofitamab through IV infusion Q3W from Cycle 2, Day 1, for up to 16 cycles (Cycle = 21 days).
  • Obinutuzumab — DRUG
    Obinutuzumab will be administered once, through IV infusion, at a fixed dose 7 days before the first dose of Glofitamab.
  • Tocilizumab — DRUG
    Tocilizumab will be administered as necessary to treat cytokine release syndrome (CRS).
  • Polatuzumab Vedotin — DRUG
    Polatuzumab vedotin will be administered in combination with Glofitamab (on different days) Q3W from Cycle 1, Day 2, for up to 12 cycles (Cycle = 21 days).
  • 89Zr-Df-IAB22M2C — DRUG
    Participants will receive 89Zr-Df-IAB22M2C (Cycle 1 only) prior to obinutuzumab pre-treatment and again on Day 10 after dosing with glofitamab, followed by PET/CT.

Study Details

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. This study includes an additional open-label imaging feasibility sub-study using a tracer in adult participants with relpased/refractory B-cell non-Hodgkin's lymphoma to image CD8+T-cells at baseline and after treatment with glofitamab, including pre-treatment with obinutuzumab.

Key Dates

Start date
May 8, 2018
Status verified
Apr 2026
Primary completion
Oct 16, 2026
Completion
Oct 16, 2026

Study Design

Enrollment
211 participants (actual)
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT

Arms

  • Experimental: Atezolizumab
    Participants will receive Glofitamab in combination with Atezolizumab up to the maximum tolerated dose (MTD).
  • Experimental: Polatuzumab Vedotin
    Participants will receive Glofitamab in combination with polatuzumab vedotin up to the MTD.
  • Experimental: Imaging Sub-study
    Participants will undergo positive-emission tomography/computed tomography (PET/CT) at screening, followed by an "Imaging Cycle," to replace Cycle 1 of the main study. Eligible participants will have the option roll-over to the atezolizumab arm of the main study from Cycle 2 onwards.

Primary Outcome Measure

Best Objective Response Rate (ORR) as Measured by Independent Review Committee (IRC) [ Time Frame: Baseline until the end of treatment (13 to 14 months), then ever 3 months until end of study visit (to occur within 4 weeks of disease progression) ]

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