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| ID | Type | Description | Link |
|---|---|---|---|
| 2016-001185-28 | EudraCT Number | ||
| 2023-505625-14-00 | Registry Identifier | EU CT Number |
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This is a Phase I/II, multicenter, open-label, dose-escalation study designed to evaluate the efficacy, safety, tolerability and pharmacokinetics (PK) of a novel T-Cell bispecific (TCB), glofitamab, administered by intravenous (IV) infusion as a single agent and in combination with obinutuzumab, following pre-treatment with a one-time, fixed dose of obinutuzumab. This entry-into-human (EIH) study is divided in 3 parts: dose escalation (Parts I and II) and dose expansion (Part III). Single-participant dose-escalation cohorts will be used in Part I, followed by conversion to multiple participant dose-escalation cohorts (Part II), in order to define a tentative maximum tolerated dose (MTD) or optimal biological dose (OBD). The expansion cohorts (Part III) will be initiated when the tentative MTD/OBD is defined, to further evaluate the safety, PK and therapeutic activity of glofitamab.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Part I: Dose Escalation | Experimental | Participants (single participant cohorts) will receive obinutuzumab pretreatment (Gpt) 1000 milligrams (mg) single dose IV infusion on Day -7 followed by glofitamab IV infusion on Day 1 and Day 8 of Cycle 1. From Cycle 2 onwards, ascending doses of glofitamab will be administered on Day 1 of every 2 week (Q2W) cycle up to Cycle 12 (24 weeks) or until unacceptable toxicity or disease progression. Glofitamab dosing will be initiated at 5 micrograms (mcg) (flat dose) followed by doses of 15 mcg, 45 mcg, 135 mcg, 405 mcg and 810 mcg. |
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| Part II: Dose Escalation | Experimental | In each treatment regimen, participants will receive Gpt 1000 mg IV infusion on Day -7; or 2000 mg either administered on Day -7, or split into two 1000 mg doses on Days -1 and -7. The first glofitamab IV infusion will be given on Day 1 of Cycle 1 and a total of 12 cycles will be administered. Monotherapy, glofitamab as a single agent: ascending doses of glofitamab administered on Day 1 of Q2W or every 3 week (Q3W) cycle until either the MTD/OBD is defined. Combination Therapy: From Cycle 2 onwards, a fixed dose of 1000 mg obinutuzumab will be administered via IV infusion in combination with ascending doses of glofitamab on Day 1 of Q3W cycle until either the MTD/OBD is defined. Step-up dosing: Q3W, participants will receive an initial low dose of glofitamab on Cycle 1 Day 1, followed by a higher dose on Cycle 1 Day 8; the total dose in Cycle 1 will not exceed the previously determined MTD. Higher doses may be explored from Cycle 2 or later cycles. |
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| Part III: Dose Expansion | Experimental | Part III will start once MTD/OBD is defined. Participants will receive Gpt 1000 mg single dose IV infusion on Day -7, followed by glofitamab at a fixed dose regimen or step-up dose regimen on a Q2W or Q3W dosing schedule as determined in Part II. A total of 12 cycles will be administered. Combination Therapy: From Cycle 2 onwards, a fixed dose of 1000 mg obinutuzumab will be administered via IV infusion in combination with glofitamab at the dosing regimen determined in Part II. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Glofitamab | Drug | Glofitamab will be administered at a dose and as per the schedule specified in the respective arms. |
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| Measure | Description | Time Frame |
|---|---|---|
| Part I and II: Percentage of Participants With Dose Limiting Toxicities (DLTs) | From Baseline up to 4 weeks | |
| Part I, II and III: Percentage of Participants With Adverse Events (AEs) | From Baseline up to 90 days after last dose of study drug or until study completion or participant withdrawal (up to 5 years) | |
| Part II: MTD or OBD of Glofitamab | From Baseline up to 4 weeks | |
| Part II: Recommended Phase II Dose (RP2D) of Glofitamab | From Baseline up to 5 years | |
| Part III: Complete Response (CR) Rate as Assessed by Independent Review Committee (IRC) According to Standard Non-hodgkin's Lymphoma (NHL) Response Criteria (Lugano Classification) | From treatment start up to 5 years | |
| Part I, II and III: Area Under the Serum Concentration Versus Time Curve (AUC) of Glofitamab | At pre-defined intervals from Cycle 1 Day 1 to Day 71 | |
| Part I, II and III: Maximum Serum Concentration (Cmax) of Glofitamab | At pre-defined intervals from Cycle 1 Day 1 to Day 198 | |
| Part I, II and III: Minimum Serum Concentration (Cmin) of Glofitamab | At pre-defined intervals from Cycle 1 Day 1 up to Day 198 | |
| Part I, II and III: Clearance (CL) of Glofitamab | At pre-defined intervals from Cycle 1 Day 1 to Day 71 |
| Measure | Description | Time Frame |
|---|---|---|
| Part I, II and III: Cmax of Obinutuzumab | Pre-dose of obinutuzumab on Day -7; pre-dose (Hr 0) of glofitamab on Day 1 of Cycle 1 | |
| Part I, II and III: Cmin of Obinutuzumab | Pre-dose of obinutuzumab on Day -7; pre-dose (Hr 0) of glofitamab on Day 1 of Cycle 1 |
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Inclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Clinical Trials | Hoffmann-La Roche | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Michigan | Ann Arbor | Michigan | 48109-0934 | United States | ||
| Washington University |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 39365960 | Derived | Phillips TJ, Carlo-Stella C, Morschhauser F, Bachy E, Crump M, Trneny M, Bartlett NL, Zaucha J, Wrobel T, Offner F, Humphrey K, Relf J, Filezac de L'Etang A, Carlile DJ, Byrne B, Qayum N, Lundberg L, Dickinson M. Glofitamab in Relapsed/Refractory Mantle Cell Lymphoma: Results From a Phase I/II Study. J Clin Oncol. 2025 Jan 20;43(3):318-328. doi: 10.1200/JCO.23.02470. Epub 2024 Oct 4. | |
| 36507690 |
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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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| Obinutuzumab | Drug | Obinutuzumab 1000 mg single dose IV infusion on Day -7; or 2000 mg single dose administered on Day -7, or split into two 1000 mg doses administered on Days -1 and -7, and per the schedule specified in the respective arms. |
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| Tocilizumab | Drug | Tocilizumab will be administered as an IV infusion, if required, for the management of severe Cytokine Release Syndrome (CRS) occurring during or after any infusion of glofitamab, as per the methods described in the Summary of Product Characteristics (SmPC) or other similar local prescribing documents. |
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| Part I, II and III: Volume of Distribution at Steady-state (Vss) of Glofitamab | At pre-defined intervals from Cycle 1 Day 1 to Day 71 |
| Part I, II and III: Half-life (t1/2) of Glofitamab | At pre-defined intervals from Cycle 1 Day 1 to Day 71 |
| Part I, II and III: Anti-drug Antibodies (ADA) to Glofitamab | Pre-dose of obinutuzumab on Day -7; pre-dose (Hr 0) of glofitamab on Day 1 of each cycle from Cycle 2 onwards for a maximum of 8-12 cycles, and at EOT/follow-up visit (up to 5 years) |
| Parts I and II: Percentage of Participants With Overall Response (Partial Response [PR] or Complete Response [CR]) as Determined by the Lugano Classification | From Baseline up to end of study or discontinuation due to disease progression (up to 5 years) |
| Part I, II and III: Percentage of Participants With PR or CR (Overall Response Rate [ORR]) as Determined by the Lugano Classifications | From Baseline up to end of study or discontinuation due to disease progression (up to 5 years) |
| Part I, II and III: Duration of Response (DOR) as Determined by the Lugano Classification | From first occurrence of documented objective response until disease progression, relapse or death due to any cause (up to 5 years) |
| Part I, II and III: Duration of Complete Response (DOCR) as Determined by the Lugano Classification | From the first occurrence of a documented, complete response, until the time of relapse or death from any cause (up to 5 years) |
| Part I, II and III: Progression-Free Survival (PFS) as Determined by the Lugano Classification | From first study treatment to the first occurrence of disease progression or death due to any cause (up to 5 years) |
| Overall Survival (OS) | From the time of first study treatment to death from any cause (up to 5 years) |
| Time to First Overall Response (TFOR) | From time of treatment start to first documented response (up to 5 years) |
| Time to First Complete Response (TFCR) | From treatment start to first documented complete response (up to 5 years) |
| Part III: Health Related Quality of Life (HRQoL) as Assessed by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-core 30 (EORTC QLQ-C30) | From baseline through follow-up or until disease progression (up to 5 years) |
| Part III: HRQoL as Assessed by the Functional Assessment of Cancer Therapy-lymphoma (FACT-lym) Scale | From baseline through follow-up or until disease progression (up to 5 years) |
| St Louis |
| Missouri |
| 63110 |
| United States |
| Mount Sinai Medical Center | New York | New York | 10029 | United States |
| MSKCC | New York | New York | 10065 | United States |
| Allegheny Health Network (Pittsburg PA) | Pittsburgh | Pennsylvania | 15212 | United States |
| Swedish Cancer Inst. | Seattle | Washington | 98104 | United States |
| Prince of Wales Hospital | Randwick | New South Wales | 2031 | Australia |
| Peter Maccallum Cancer Centre | Melbourne | Victoria | 3000 | Australia |
| Cliniques Universitaires St-Luc | Brussels | 1200 | Belgium |
| UZ Gent | Ghent | 9000 | Belgium |
| Princess Margaret Cancer Center | Toronto | Ontario | M5G 1Z5 | Canada |
| Vseobecna Fakultni Nemocnice v Praze, I. Interni Klinika - Klinika Hematoonkologie VFN a 1. LF UK | Prague | 128 08 | Czechia |
| Rigshospitalet | København Ø | 2100 | Denmark |
| Helsinki University Central Hospital | Helsinki | 00029 | Finland |
| Hopital Henri Mondor | Créteil | 94010 | France |
| Hopital Claude Huriez | Lille | 59037 | France |
| CHU Saint Eloi | Montpellier | 34295 | France |
| Ch Lyon Sud | Pierre-Bénite | 69495 | France |
| CHU DE RENNES - CHU Pontchaillou | Rennes | 35033 | France |
| AUSL della Romagna | Ravenna | Emilia-Romagna | 48121 | Italy |
| Fond. IRCCS Istituto Nazionale Tumori | Milan | Lombardy | 20133 | Italy |
| Istituto Clinico Humanitas | Rozzano | Lombardy | 20089 | Italy |
| Auckland Cancer Trial Centre | Auckland | 1023 | New Zealand |
| Uniwersyteckie Centrum Kliniczne | Gda?sk | 80-214 | Poland |
| Uniwersytecki Szpital Kliniczny w Poznaniu | Późna | 60-569 | Poland |
| Uniwersytecki Szpital Kliniczny im. Jana Mikulicza-Radeckiego we Wroclawiu | Wroc?aw | 50-367 | Poland |
| Hospital Universitari Germans Trias i Pujol | Badalona | Barcelona | 08915 | Spain |
| Hospital Duran i Reynals L'Hospitalet | L'Hospitalet de Llobregat | Barcelona | 08908 | Spain |
| Hospital Universitario Marques de Valdecilla | Santander | Cantabria | 39008 | Spain |
| Hospital del Mar | Barcelona | 08003 | Spain |
| Hospital Universitari Vall d'Hebron | Barcelona | 08035 | Spain |
| Hospital Univ. 12 de Octubre | Madrid | 28041 | Spain |
| China Medical University Hospital | Taichung | 404 | Taiwan |
| National Taiwan Universtiy Hospital | Taipei | 100 | Taiwan |
| Derived |
| Dickinson MJ, Carlo-Stella C, Morschhauser F, Bachy E, Corradini P, Iacoboni G, Khan C, Wrobel T, Offner F, Trneny M, Wu SJ, Cartron G, Hertzberg M, Sureda A, Perez-Callejo D, Lundberg L, Relf J, Dixon M, Clark E, Humphrey K, Hutchings M. Glofitamab for Relapsed or Refractory Diffuse Large B-Cell Lymphoma. N Engl J Med. 2022 Dec 15;387(24):2220-2231. doi: 10.1056/NEJMoa2206913. Epub 2022 Dec 11. |
| 34953862 | Derived | Frances N, Bacac M, Bray-French K, Christen F, Hinton H, Husar E, Quackenbush E, Schafer M, Schick E, Vyver AV, Richter WF. Novel in Vivo and in Vitro Pharmacokinetic/Pharmacodynamic-Based Human Starting Dose Selection for Glofitamab. J Pharm Sci. 2022 Apr;111(4):1208-1218. doi: 10.1016/j.xphs.2021.12.019. Epub 2021 Dec 22. |
| 34941996 | Derived | Broske AE, Korfi K, Belousov A, Wilson S, Ooi CH, Bolen CR, Canamero M, Alcaide EG, James I, Piccione EC, Carlile DJ, Dimier N, Umana P, Bacac M, Weisser M, Dickinson M. Pharmacodynamics and molecular correlates of response to glofitamab in relapsed/refractory non-Hodgkin lymphoma. Blood Adv. 2022 Feb 8;6(3):1025-1037. doi: 10.1182/bloodadvances.2021005954. |
| 33739857 | Derived | Hutchings M, Morschhauser F, Iacoboni G, Carlo-Stella C, Offner FC, Sureda A, Salles G, Martinez-Lopez J, Crump M, Thomas DN, Morcos PN, Ferlini C, Broske AE, Belousov A, Bacac M, Dimier N, Carlile DJ, Lundberg L, Perez-Callejo D, Umana P, Moore T, Weisser M, Dickinson MJ. Glofitamab, a Novel, Bivalent CD20-Targeting T-Cell-Engaging Bispecific Antibody, Induces Durable Complete Remissions in Relapsed or Refractory B-Cell Lymphoma: A Phase I Trial. J Clin Oncol. 2021 Jun 20;39(18):1959-1970. doi: 10.1200/JCO.20.03175. Epub 2021 Mar 19. |
| 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 |
| C543332 | obinutuzumab |
| C502936 | tocilizumab |
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