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| ID | Type | Description | Link |
|---|---|---|---|
| 2017-003648-18 | EudraCT Number |
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This is a phase 1B, multi-center, dose-finding study of glofitamab administered in combination with obinutuzumab (Gazyva; [G]), rituximab (R) and standard doses of CHOP (G/R-CHOP or R-CHOP) in participants with r/r NHL and G/R CHOP or Pola-R-CHP in participants with untreated diffuse large B-cell lymphoma (DLBCL). Evaluating the safety, preliminary activity, pharmacokinetic (PK), and pharmacodynamic effects of this combination will be the main objectives of this study. The study is divided in two parts:
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Part 1: Dose Escalation r/r NHL | Experimental | Dose finding in participants with r/r NHL: the study will explore different doses of glofitamab in the induction period, starting at a dose of 70 mcg administered in combination with standard of care doses of G/R CHOP and R-CHOP every 3 weeks (Q3W). Participants with r/r NHL will receive 6 cycles of induction treatment (G/R-CHOP). Glofitamab will be administered using step-up dosing for Cycle 2 on Days 8 and 15, followed by single doses on Day 8 for Cycles 3-6. Participants who achieve a complete response (CR), partial response (PR), or stable disease (SD) at the end of induction (EOInd) may optionally receive post-induction treatment (referred to as maintenance) with glofitamab alone. The use of G versus R in Cycle 1 will be compared in parallel dose escalation cohorts. |
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| Part 2: DLBCL G/R-CHOP | Experimental | Participants with untreated DLBCL will receive G-CHOP or R-CHOP in Cycle 1, followed by G/R-CHOP + glofitamab for subsequent cycles. Glofitamab will be administered using step-up dosing for Cycle 2 on Days 8 and 15, followed by single doses on Day 8 for Cycles 3-6 (up to 8). The starting dose of glofitamab for each arm may be one or more levels below the MTD/OBD determined in Part I. |
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| Part 2: DLBCL Pola-R-CHP | Experimental | Participants with untreated DLBCL will receive Pola-R-CHP + glofitamab on Day 1 of each 21-day cycle for a maximum of 6 cycles. Glofitamab will be administered using step-up dosing for Cycle 2 on Days 8 and 15, followed by single doses on Day 8 for Cycles 3-6. The starting dose of glofitamab for each arm may be one or more levels below the MTD/OBD determined in Part I. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Glofitamab | Drug | Glofitamab will be administered intravenously (IV) as a step-up dose for Cycle 2 on Days 8 and 15, and as a single dose from Cycle 3 onwards. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Part I: Percentage of Participants with Dose Limiting Toxicities (DLTs) | Up to 29 months | |
| Part I and II: Percentage of Participants with Adverse Events | Up to 29 months |
| Measure | Description | Time Frame |
|---|---|---|
| Parts I and II: Percentage of Participants with a Complete Response (CR) as Assessed by the Investigator using Modified Lugano 2014 Criteria | Up to 29 months | |
| Parts I and II: Percentage of Participants with Overall Response (Partial Response [PR] or Complete Response [CR]) |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Clinical Trials | Hoffmann-La Roche | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Alabama Medical Center | Birmingham | Alabama | 35294 | United States | ||
| Levine Cancer Institute |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 40749164 | Derived | Sam J, Leclercq-Cohen G, Gebhardt S, Surowka M, Herter S, Lechner K, Relf J, Briner S, Varol A, Appelt B, Domocos I, Nicolini V, Bez M, Bommer E, Jenni S, Schoenle A, Le Clech M, Colombetti S, Klein C, Umana P, Lundberg P, Korfi K, Bottos A, Bacac M. Preclinical advances in glofitamab combinations: a new frontier for non-Hodgkin lymphoma. Blood. 2025 Oct 9;146(15):1824-1836. doi: 10.1182/blood.2025028863. |
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| Obinutuzumab (G) | Drug | Obinutuzumab 1000 mg single dose IV infusion on Day 1 of Cycle 1 only |
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| Rituximab (R) | Drug | Rituximab will be administered as an IV infusion at a dose of 375 mg/m^2 on Day 1 of each 21-day cycle starting from Cycle 1 to Cycle 6 (Part 1) or from Cycles 1-6 (up to 8) (Part 2: DLBCL R-CHOP). |
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| Tocilizumab | Drug | Tocilizumab will be administered as an IV infusion as per the methods described in the Summary of Product Characteristics (SmPC) or other similar local prescribing documents. Tocilizumab will be given as rescue medication. |
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| Cyclophosphamide | Drug | Cyclophosphamide 750 mg/m^2 administered IV on Day 1 of each 21-day cycle |
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| Doxorubicin | Drug | Doxorubicin 50 mg/m^2 administered IV on Day 1 of each 21-day cycle |
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| Vincristine | Drug | Vincristine 1.4 mg/m^2 administered by IV push on Day 1 of each 21-day cycle with a recommended cap of 2 mg |
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| Prednisone | Drug | Prednisone 100 mg/day orally on Days 1-5 (prednisone on Day 1 may be administered IV, with the remaining doses on Days 2-5 to be administered orally) of each 21-day cycle |
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| Polatuzumab vedotin | Drug | Polatuzumab vedotin 1.8 mg/kg administered IV on Day 1 of each 21-day cycle |
|
| Up to 29 months |
| Parts I and II: Duration of Response (DOR) | Up to 29 months |
| Duration of CR | Up to 29 months |
| Progression-Free Survival (PFS) | Up to 29 months |
| Overall Survival (OS) | Up to 29 months |
| Time to First Complete Response (TFCR) | Up to 29 months |
| Time to First Response (TFOR) | Up to 29 months |
| Parts I and II: Area Under the Serum Concentration Versus Time Curve (AUC) of Glofitamab | Cycle 1 Day 1 up to 29 months |
| Parts I and II: Time to Maximum Serum Concentration (tmax) of Glofitamab | Cycle 1 Day 1 up to 29 months |
| Parts I and II: Maximum Serum Concentration (Cmax) of Glofitamab | Cycle 1 Day 1 up to 29 months |
| Parts I and II: Minimum Serum Concentration (Cmin) of Glofitamab | Cycle 1 Day 1 up to 29 months |
| Change from Baseline in T-cell Activation Markers | Up to 29 months |
| Charlotte |
| North Carolina |
| 28204 |
| United States |
| Fox Chase-Temple Cancer Center | Philadelphia | Pennsylvania | 19111 | United States |
| Peter Maccallum Cancer Centre | Melbourne | Victoria | 3000 | Australia |
| Princess Margaret Cancer Center | Toronto | Ontario | M5G 1Z5 | Canada |
| Rigshospitalet | København Ø | 2100 | Denmark |
| Hopital Claude Huriez | Lille | 59037 | France |
| Hopital Hotel Dieu Et Hme | Nantes | 44093 | France |
| Centre Henri Becquerel | Rouen | 76038 | France |
| Universitätsklinikum Erlangen, Translational Research Center (TRC), Medizin 5 | Erlangen | 91054 | Germany |
| Universitätsklinikum Freiburg | Freiburg im Breisgau | 79106 | Germany |
| Universitätsklinikum Ulm | Ulm | 89081 | Germany |
| Universitätsklinikum Würzburg | Würzburg | 97080 | Germany |
| Istituto Nazionale Tumori Irccs Fondazione g. Pascale | Naples | Campania | 80131 | Italy |
| UO Ematologia, Ospedale S.Maria delle Croci | Ravenna | Emilia-Romagna | 48121 | Italy |
| Asst Papa Giovanni Xxiii | Bergamo | Lombardy | 24127 | Italy |
| Istituto Clinico Humanitas | Rozzano | Lombardy | 20089 | Italy |
| Hospital Universitari Vall d'Hebron | Barcelona | 08035 | Spain |
| Hospital Clínic i Provincial | Barcelona | 08036 | Spain |
| START Madrid-FJD, Hospital Fundacion Jimenez Diaz | Madrid | 28040 | Spain |
| University College London Hospitals NHS Foundation Trust | London | W1T 7HA | United Kingdom |
| Nottingham University Hospitals NHS Trust - City Hospital | Nottingham | NG5 1PB | United Kingdom |
| ID | Term |
|---|---|
| D016393 | Lymphoma, B-Cell |
| 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 |
| C543332 | obinutuzumab |
| D000069283 | Rituximab |
| C502936 | tocilizumab |
| D003520 | Cyclophosphamide |
| D004317 | Doxorubicin |
| D014750 | Vincristine |
| D011241 | Prednisone |
| C000600736 | polatuzumab vedotin |
| ID | Term |
|---|---|
| D058846 | Antibodies, Monoclonal, Murine-Derived |
| D000911 | Antibodies, Monoclonal |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
| D007162 | Immunoproteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |
| D010752 | Phosphoramide Mustards |
| D009588 | Nitrogen Mustard Compounds |
| D009150 | Mustard Compounds |
| D006846 | Hydrocarbons, Halogenated |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D063088 | Phosphoramides |
| D009943 | Organophosphorus Compounds |
| D003630 | Daunorubicin |
| D018943 | Anthracyclines |
| D009279 | Naphthacenes |
| D011084 | Polycyclic Aromatic Hydrocarbons |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D011083 | Polycyclic Compounds |
| D000617 | Aminoglycosides |
| D006027 | Glycosides |
| D002241 | Carbohydrates |
| D014748 | Vinca Alkaloids |
| D046948 | Secologanin Tryptamine Alkaloids |
| D026121 | Indole Alkaloids |
| D000470 | Alkaloids |
| D006571 | Heterocyclic Compounds |
| D007211 | Indoles |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D054836 | Indolizidines |
| D007212 | Indolizines |
| D011244 | Pregnadienediols |
| D011245 | Pregnadienes |
| D011278 | Pregnanes |
| D013256 | Steroids |
| D000072473 | Fused-Ring Compounds |
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