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
Phase 1
Active, not recruiting
- Conditions
- Non-Hodgkins Lymphoma
- Interventions
- Registration Number
- NCT03533283
- Lead Sponsor
- Hoffmann-La Roche
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 211
Inclusion Criteria
Not provided
Exclusion Criteria
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Polatuzumab Vedotin Obinutuzumab Participants will receive Glofitamab in combination with polatuzumab vedotin up to the MTD. Polatuzumab Vedotin Tocilizumab Participants will receive Glofitamab in combination with polatuzumab vedotin up to the MTD. Polatuzumab Vedotin Polatuzumab Vedotin Participants will receive Glofitamab in combination with polatuzumab vedotin up to the MTD. Imaging Sub-study Glofitamab 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. Imaging Sub-study Obinutuzumab 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. Imaging Sub-study 89Zr-Df-IAB22M2C 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. Atezolizumab Glofitamab Participants will receive Glofitamab in combination with Atezolizumab up to the maximum tolerated dose (MTD). Atezolizumab Atezolizumab Participants will receive Glofitamab in combination with Atezolizumab up to the maximum tolerated dose (MTD). Atezolizumab Obinutuzumab Participants will receive Glofitamab in combination with Atezolizumab up to the maximum tolerated dose (MTD). Atezolizumab Tocilizumab Participants will receive Glofitamab in combination with Atezolizumab up to the maximum tolerated dose (MTD). Polatuzumab Vedotin Glofitamab Participants will receive Glofitamab in combination with polatuzumab vedotin up to the MTD.
- Primary Outcome Measures
Name Time Method Best Objective Response Rate (ORR) as Measured by Independent Review Committee (IRC) 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) Dose Limiting Toxicities (DLTs) Atezolizumab Arm: During DLT period of 21 days (or up to 42 days in the case of cycle delay), starting on Day 1, Cycle 2; Polatuzumab Vedotin Arm: During 5-week DLT period starting Cycle 1, Day 8
- Secondary Outcome Measures
Name Time Method Elimination Half-Life (T1/2) of Glofitamab Administered in Combination with Atezolizumab or Polatuzumab Vedotin At pre-defined intervals through the end of study (EoS) visit (to occur within 4 weeks of disease progression) Area Under the Concentration-Time Curve (AUC) for Glofitamab Administered in Combination with Atezolizumab or Polatuzumab Vedotin At pre-defined intervals through the end of study (EoS) visit (to occur within 4 weeks of disease progression) Time to First Overall Response (TFOR) 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) Overall Survival (OS) 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) Percentage of Participants with Adverse Events (AEs) 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) Incidence and Severity of Cytokine Release Syndrome (CRS) Following Glofitamab Administration 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) Anti-Drug Antibody (ADA) Formation 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) SUVpeak of 89Zr-Df-IAB22M2C (Imaging Sub-study From baseline to Day 13 Best ORR as Measured by Investigator 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) Best Complete Response (CR) Rate, as Assessed by Fluorodeoxyglucose-Positron Emission Tomography/Computed Tomography (FDG-PET/CT) Scan 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) Duration of Complete Response (DOCR) 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) Duration of Response (DOR) 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) Progression-Free Survival (PFS) 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) Event-Free Survival (EFS) 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) Time to First Complete Response (TFCR) 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) Time to Maximum Observed Serum Concentration (Tmax) of Glofitamab Administered in Combination with Atezolizumab or Polatuzumab Vedotin At pre-defined intervals through the end of study (EoS) visit (to occur within 4 weeks of disease progression) Maximum Observed Serum Concentration (Cmax) of Glofitamab Administered in Combination with Atezolizumab or Polatuzumab Vedotin At pre-defined intervals through the end of study (EoS) visit (to occur within 4 weeks of disease progression) Minimum Serum Concentration (Cmin) of Glofitamab Administered in Combination with Atezolizumab or Polatuzumab Vedotin At pre-defined intervals through the end of study (EoS) visit (to occur within 4 weeks of disease progression) Clearance (CL) of Glofitamab Administered in Combination with Atezolizumab or Polatuzumab Vedotin At pre-defined intervals through the end of study (EoS) visit (to occur within 4 weeks of disease progression) Volume of Distribution at Steady-State (Vss) of Glofitamab Administered in Combination with Atezolizumab or Polatuzumab Vedotin At pre-defined intervals through the end of study (EoS) visit (to occur within 4 weeks of disease progression) CD8-Positive T Cell Proliferation At pre-defined intervals during the study treatment period (up to 17 cycles; Cycle = 21 days) CD20-Positive B-Cell Reduction At pre-defined intervals during the study treatment period (up to 17 cycles; Cycle = 21 days) SUVmax of 89Zr-Df-IAB22M2C (Imaging Sub-study) From baseline to Day 13 SUVmean of 89Zr-Df-IAB22M2C (Imaging Sub-study) From baseline to Day 13 Tumor Volume Based on 89Zr-Df-IAB22M2C PET-uptake (Imaging Sub-study) From baseline to Day 13 Quantitation of CD8+ Cells on Biopsy Samples (Imaging Sub-study) From baseline to Day 13
Trial Locations
- Locations (19)
Aarhus Universitetshospital Skejby
🇩🇰Aarhus N, Denmark
Rigshospitalet
🇩🇰København Ø, Denmark
Odense Universitetshospital
🇩🇰Odense C, Denmark
Hadassah Ein Karem Hospital
🇮🇱Jerusalem, Israel
Rabin Medical Center-Beilinson Campus
🇮🇱Petach Tikva, Israel
Chaim Sheba Medical Center
🇮🇱Ramat-Gan, Israel
Istituto Nazionale Tumori Irccs Fondazione g. Pascale
🇮🇹Napoli, Campania, Italy
Policlinico S.Orsola-Malpighi
🇮🇹Bologna, Emilia-Romagna, Italy
Asst Papa Giovanni Xxiii
🇮🇹Bergamo, Lombardia, Italy
Fond. IRCCS Istituto Nazionale Tumori
🇮🇹Milano, Lombardia, Italy
Hospital Clinico Universitario Virgen de la Victoria
🇪🇸Malaga, Spain
Hospital Universitari Vall d'Hebron
🇪🇸Barcelona, Spain
Hospital Duran i Reynals
🇪🇸Barcelona, Spain
Hospital Clinico Universitario de Valencia
🇪🇸Valencia, Spain
University College London Hospitals NHS Foundation Trust
🇬🇧London, United Kingdom
UZ Gent
🇧🇪Gent, Belgium
START Madrid-FJD, Hospital Fundacion Jimenez Diaz
🇪🇸Madrid, Spain
The HOPE Clinical Trials Unit
🇬🇧Leicester, United Kingdom
The Newcastle upon Tyne Hospitals NHS Foundation Trust
🇬🇧Newcastle upon Tyne, United Kingdom