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| ID | Type | Description | Link |
|---|---|---|---|
| 2019-000416-28 | EudraCT Number | ||
| 2022-502616-37-00 | Registry Identifier | EU CT Number |
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This is a phase I/II, open-label, dose-escalation study designed to evaluate the safety, tolerability, and efficacy of englumafusp alfa (RO7227166) in participants with relapsed/refractory Non-Hodgkin's Lymphoma (r/r NHL). Englumafusp alfa will be administered by intravenous (IV) infusion in combination with obinutuzumab and in combination with glofitamab. A fixed dose of obinutuzumab (Gpt; pre-treatment) will be administered up to seven days prior to the first administration of englumafusp alfa and seven days prior to the first administration of glofitamab. This entry-into-human study is divided into a dose-escalation stage (Part I and Part II) and a dose expansion stage (Part III).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Part I | Experimental | Combination Dose-Escalation: Mixed r/r NHL participants will receive a fixed dose of obinutuzumab up to seven days prior to first administration of englumafusp alfa. Englumafusp alfa will be administered by intravenous (IV) infusion in combination with obinutuzumab in a three-weekly schedule (Q3W). |
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| Part II | Experimental | Combination Dose-Escalation: Mixed r/r participants and participants with mixed r/r mantle cell lymphoma (MCL) and Richters transformation will receive a fixed dose of obinutuzumab seven days prior to first administration of englumafusp alfa. Englumafusp alfa will be administered by IV infusion in combination with glofitamab in a three-weekly schedule (Q3W). |
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| Part III | Experimental | Dose-Expansion Stage: Participants with r/r diffuse large B-cell lymphoma not otherwise specified (DLBCL NOS), high-grade B-cell lymphoma (HGBCL), primary mediastinal B-cell lymphoma (PMBCL), and DLBCL arising from FL (transformed FL) will receive englumafusp alfa administered by IV infusion in combination with glofitamab in a three-weekly schedule (Q3W). |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Englumafusp alfa | Drug | Englumafusp alfa will be administered by intravenous (IV) infusion three-weekly (Q3W) in combination with a fixed dose of obinutuzumab (Part I) and in combination with a fixed dose of glofitamab (Part II and Part III). |
| Measure | Description | Time Frame |
|---|---|---|
| Nature and frequency of dose-limiting toxicities (DLTs) | 28 days in Part I and Part II | |
| Proportion of Participants with Adverse Event (AE) | Incidence, nature, and severity of AEs graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0 | Part I: Up to 24 months; Part II: Up to 18 months; Part III: Up to 9 months or up to 18 months |
| Overall Response Rate (ORR) | Part I: Up to 24 months; Part II: Up to 18 months; Part III: Up to 9 months or up to 18 months | |
| Disease Control Rate (DCR) | Part I: Up to 24 months; Part II: Up to 18 months; Part III: Up to 9 months or up to 18 months | |
| Duration of Response (DOR) | After end of Study approximately every 3 months until death, loss to follow-up or study termination | |
| Progression-free Survival (PFS) | After end of Study approximately every 3 months until death, loss to follow-up or study termination | |
| Overall Survival (OS) | After end of Study approximately every 3 months until death, loss to follow-up or study termination | |
| Complete Response (CR) | Part III: Up to 9 months or up to 18 months |
| Measure | Description | Time Frame |
|---|---|---|
| Total exposure (area under the concentration time curve [AUC]) of englumafusp alfa in combination with obinutuzumab and glofitamab | Part I: Up to 24 months; Part II: Up to 18 months; Part III: Up to 9 months or up to 18 months | |
| Maximum serum concentration (peak concentration, Cmax) of englumafusp alfa in combination with obinutuzumab and glofitamab |
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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 |
|---|---|---|---|---|---|---|
| City of Hope Medical Center | Pasadena | California | 91105 | United States | ||
| University of California San Francisco |
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 | A fixed dose of obinutuzumab will be administered up to 7 days prior to the first dose of englumafusp alfa, then in combination with obinutuzumab Q3W (Part I). A fixed dose of obinutuzumab will be administered up to 7 days prior to the first dose of englumafusp alfa or between Day -3 and -7 (Part II and Part III). |
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| Glofitamab | Drug | A fixed dose of glofitamab will be administered Q3W in combination with englumafusp alfa in Part II and Part III |
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| Tocilizumab | Drug | Participants will receive IV tocilizumab as needed to treat cytokine release syndrome (CRS). |
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| Part I: Up to 24 months; Part II: Up to 18 months; Part III: Up to 9 months or up to 18 months |
| Minimum serum concentration (trough concentration, Cmin) of englumafusp alfa in combination with obinutuzumab and glofitamab | Part I: Up to 24 months; Part II: Up to 18 months; Part III: Up to 9 months or up to 18 months |
| Clearance (CL) of englumafusp alfa in combination with obinutuzumab and glofitamab | Part I: Up to 24 months; Part II: Up to 18 months; Part III: Up to 9 months or up to 18 months |
| Volume of distribution of steady state (Vss) and half-life (t1/2) of englumafusp alfa in combination with obinutuzumab and glofitamab | Part I: Up to 24 months; Part II: Up to 18 months; Part III: Up to 9 months or up to 18 months |
| ORR | Part I: Up to 24 months; Part II: Up to 18 months; Part III: Up to 9 months or up to 18 months |
| DCR | Part I: Up to 24 months; Part II: Up to 18 months; Part III: Up to 9 months or up to 18 months |
| DOR | After end of Study approximately every 3 months until death, loss to follow-up or study termination |
| PFS | After end of Study approximately every 3 months until death, loss to follow-up or study termination |
| OS | After end of Study approximately every 3 months until death, loss to follow-up or study termination |
| Proportion of Participants with Adverse Event (AE) | Incidence, nature, and severity of AEs graded according to the NCI CTCAE v5.0 | After end of Study approximately every 3 months until death, loss to follow-up or study termination |
| Total exposure (area under the concentration time curve [AUC]) of englumafusp alfa in combination with glofitamab | Part III: Up to 9 months or up to 18 months |
| Maximum serum concentration (peak concentration, Cmax) of englumafusp alfa in combination with glofitamab | Part III: Up to 9 months or up to 18 months |
| Minimum serum concentration (trough concentration, Cmin) of englumafusp alfa in combination with glofitamab | Part III: Up to 9 months or up to 18 months |
| Clearance (CL) of englumafusp alfa in combination with glofitamab | Part III: Up to 9 months or up to 18 months |
| Volume of distribution of steady state (Vss) and half-life (t1/2) of englumafusp alfa in combination with glofitamab Part I/II/III | Part III: Up to 9 months or up to 18 months |
| T-cell and Natural killer (NK)-cell status in blood, using markers of T and NK-cell lineage, function and activation including, but not limited to, CD3, CD8, 41BB, and Ki67 expression | Part I: Up to 24 months; Part II: Up to 18 months; Part III: Up to 9 months or up to 18 months |
| B-cell reduction in blood and tumor tissue | Part I: Up to 24 months; Part II: Up to 18 months; Part III: Up to 9 months or up to 18 months |
| Change from Baseline in englumafusp alfa Anti-Drug Antibody (ADA) Titer | Part 1: Up to 24 months; Part ll/lll: Up to 18 months |
| Time to First Complete Response (TFCR) | Up to 18 months |
| Time to First Overall Response (TFOR) | Up to 18 months |
| Duration of Complete Response (DOCR) | Part III: Up to 9 months or up to 18 months |
| Change from Baseline in Physical Function, Role Function, and Health-Related Quality of Life (HRQoL) Based on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) | Part III: Up to 9 months or up to 18 months |
| Change from Baseline in Physical Function, Role Function, and HRQoL According to the Functional Assessment of Cancer Therapy-Lymphoma (FACT-Lym) Lymphoma Scale | Part III: Up to 9 months or up to 18 months |
| San Francisco |
| California |
| 94158 |
| United States |
| Washington University School of Medicine | St Louis | Missouri | 63110 | United States |
| The University of Texas MD Anderson Cancer Center | Houston | Texas | 77030-4009 | United States |
| Peter Maccallum Cancer Centre | Melbourne | Victoria | 3000 | Australia |
| The Alfred Hospital | Melbourne | Victoria | 3004 | Australia |
| UZ Gent | Ghent | 9000 | Belgium |
| Queen Elizabeth II Health Sciences Centre | Halifax | Nova Scotia | B3H 2Y9 | Canada |
| Jewish General Hospital | Montreal | Quebec | H3T 1E2 | Canada |
| Beijing Cancer Hospital | Beijing | 100142 | China |
| Shandong Cancer Hospital | Jinan | 250117 | China |
| Fudan University Shanghai Cancer Center | Shanghai | 201315 | China |
| The First Affiliated Hospital of Xiamen University | Xiamen | 361003 | China |
| Aarhus Universitetshospital Skejby | Aarhus N | 8200 | Denmark |
| Rigshospitalet | København Ø | 2100 | Denmark |
| Odense Universitetshospital | Odense C | 5000 | Denmark |
| CHRU de Lille | Lille | 59037 | France |
| CHU Montpellier - Saint ELOI | Montpellier | 34295 | France |
| Centre Hospitalier Lyon Sud | Pierre-Bénite | 69495 | France |
| CHU DE RENNES - CHU Pontchaillou | Rennes | 35033 | France |
| Istituto Nazionale Tumori Irccs Fondazione g. Pascale | Naples | Campania | 80131 | Italy |
| Asst Papa Giovanni Xxiii | Bergamo | Lombardy | 24127 | Italy |
| Irccs Istituto Europeo Di Oncologia (IEO) | Milan | Lombardy | 20141 | Italy |
| Istituto Clinico Humanitas | Rozzano | Lombardy | 20089 | Italy |
| Auckland City Hospital, Cancer and Blood Research | Auckland | 1023 | New Zealand |
| Waikato Hospital - Cancer and Blood Research Trials Unit | Hamilton | 3204 | New Zealand |
| Pusan National University Hospital | Busan | 49241 | South Korea |
| Seoul National University Hospital | Seoul | 03080 | South Korea |
| Asan Medical Center | Seoul | 05505 | South Korea |
| Samsung Medical Center | Seoul | 06351 | South Korea |
| Hospital Universitari Vall d'Hebron | Barcelona | 08035 | Spain |
| Hospital Univ. 12 de Octubre | Madrid | 28041 | Spain |
| Hospital Clinico Universitario Virgen de la Victoria | Málaga | 29010 | Spain |
| The HOPE Clinical Trials Unit | Leicester | LE1 5WW | United Kingdom |
| University College London Hospitals NHS Foundation Trust | London | W1T 7HA | 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 |
|---|---|
| C543332 | obinutuzumab |
| D000410 | Alanine Transaminase |
| C000720108 | glofitamab |
| C502936 | tocilizumab |
| ID | Term |
|---|---|
| D000637 | Transaminases |
| D019884 | Nitrogenous Group Transferases |
| D014166 | Transferases |
| D004798 | Enzymes |
| D045762 | Enzymes and Coenzymes |
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