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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Atezolizumab | Experimental | Participants will receive Glofitamab in combination with Atezolizumab up to the maximum tolerated dose (MTD). |
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| Polatuzumab Vedotin | Experimental | Participants will receive Glofitamab in combination with polatuzumab vedotin up to the MTD. |
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| Imaging Sub-study | Experimental | 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. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
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Main Inclusion Criteria
Inclusion Criteria Specific to Imaging Substudy
Main Exclusion Criteria
Exclusion Criteria Specific to Imaging Substudy
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| Name | Affiliation | Role |
|---|---|---|
| Clinical Trials | Hoffmann-La Roche | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| UZ Gent | Ghent | 9000 | Belgium | |||
| Aarhus Universitetshospital Skejby |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 41115257 | Derived | Hutchings M, Sureda A, Bosch F, Larsen TS, Corradini P, Avigdor A, Terol MJ, Dominguez AR, Pinto A, Skarbnik A, Cordoba R, Jorgensen JM, Zinzani PL, Leung W, Bottos A, Li D, Relf J, Tandon M, Sellam G, Gritti G. Efficacy and Safety of Glofitamab Plus Polatuzumab Vedotin in Relapsed/Refractory Large B-Cell Lymphoma Including High-Grade B-Cell Lymphoma: Results From a Phase Ib/II Trial. J Clin Oncol. 2025 Dec 20;43(36):3788-3798. doi: 10.1200/JCO-25-00992. Epub 2025 Oct 20. |
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For eligible studies, qualified researchers may request access to individual patient level clinical data. See Roche's commitment to transparency of clinical study information here: https://go.roche.com/data\_sharing
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| 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). |
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| Obinutuzumab | Drug | Obinutuzumab will be administered once, through IV infusion, at a fixed dose 7 days before the first dose of Glofitamab. |
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| Tocilizumab | Drug | Tocilizumab will be administered as necessary to treat cytokine release syndrome (CRS). |
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| 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). |
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| 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. |
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| 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 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) |
| 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 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 |
| SUVpeak 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 |
| Aarhus N |
| 8200 |
| Denmark |
| Rigshospitalet | København Ø | 2100 | Denmark |
| Odense Universitetshospital | Odense C | 5000 | Denmark |
| Hadassah Ein Karem Hospital | Jerusalem | 9112001 | Israel |
| Rabin Medical Center-Beilinson Campus | Petah Tikva | 4941492 | Israel |
| Chaim Sheba Medical Center | Ramat Gan | 52621 | Israel |
| Istituto Nazionale Tumori Irccs Fondazione g. Pascale | Naples | Campania | 80131 | Italy |
| Policlinico S.Orsola-Malpighi | Bologna | Emilia-Romagna | 40138 | Italy |
| Asst Papa Giovanni Xxiii | Bergamo | Lombardy | 24127 | Italy |
| Fond. IRCCS Istituto Nazionale Tumori | Milan | Lombardy | 20133 | Italy |
| Hospital Universitari Vall d'Hebron | Barcelona | 08035 | Spain |
| Hospital Duran i Reynals | Barcelona | 08907 | Spain |
| START Madrid-FJD, Hospital Fundacion Jimenez Diaz | Madrid | 28040 | Spain |
| Hospital Clinico Universitario Virgen de la Victoria | Málaga | 29010 | Spain |
| Hospital Clinico Universitario de Valencia | Valencia | 46010 | Spain |
| The HOPE Clinical Trials Unit | Leicester | LE1 5WW | United Kingdom |
| University College London Hospitals NHS Foundation Trust | London | W1T 7HA | United Kingdom |
| The Newcastle upon Tyne Hospitals NHS Foundation Trust | Newcastle upon Tyne | NE1 4LP | United Kingdom |
| ID | Term |
|---|---|
| D008228 | Lymphoma, Non-Hodgkin |
| ID | Term |
|---|---|
| D008223 | Lymphoma |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D008232 | Lymphoproliferative Disorders |
| D008206 | Lymphatic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D007160 | Immunoproliferative Disorders |
| D007154 | Immune System Diseases |
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| ID | Term |
|---|---|
| C000720108 | glofitamab |
| C000594389 | atezolizumab |
| C543332 | obinutuzumab |
| C502936 | tocilizumab |
| C000600736 | polatuzumab vedotin |
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