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The study was terminated due to sponsor portfolio re-alignment.
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This is a first-in human, open-label, Phase 1 dose-escalation study in order to determine the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D) for intravenous (IV) and/or subcutaneous (SC) dosing schemes of this combination treatment, and to evaluate the safety, tolerability, pharmacokinetics, and preliminary anti-tumor activity of this combination treatment in participants with relapsed/refractory B-cell non Hodgkin lymphoma (r/r NHL).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Parts I-III: Dose-escalation of RO7443904 | Experimental | The dose-escalation of RO7443904 and glofitamab will take place every three weeks (Q3W) with obinutuzumab pre-treatment. |
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| Part IV: Dose-expansion of RO7443904 | Experimental | Part IV of this study will evaluate selected dose levels of RO7443904 in combination with glofitamab from Parts I-III in a Q3W regimen with obinutuzumab pre-treatment. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| RO7443904 | Drug | RO7443904 will be administered by subcutaneous (SC) or IV infusion on Cycle (C) 1 Day (D) 10, C2D3, and C2D8. From C3 onward, RO7443904 will be given every 3 weeks (Q3W), for up to 12 cycles (C = 21 days). |
| Measure | Description | Time Frame |
|---|---|---|
| Nature and frequency of dose-limiting toxicities (DLTs) | From 3 weeks (21 days) from the first administration of RO7443904 (Cycle 2 Day 8) to 1 week after the second administration of RO7443904 (Cycle 3 Day 8) | |
| Incidence, nature, and severity of AEs | graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0 and for cytokine-release syndrome (CRS) and neurotoxicity (immune effector cell-associated neurotoxicity syndrome; ICANS) according to the American Society for Transplantation and Cellular Therapy (ASTCT) consensus grading | Up to 4 weeks after the last study treatment dose |
| Measure | Description | Time Frame |
|---|---|---|
| Maximum concentration (Cmax) of RO7443904 | Up to 9 months | |
| Area under the curve (AUC) of RO7443904 | Up to 9 months | |
| Clearance (CL) of RO7443904 |
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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 |
|---|---|---|---|---|---|---|
| MSKCC | New York | New York | 10065 | United States | ||
| Cleveland Clinic Foundation; Hematology and Oncology |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 38437725 | Derived | Sam J, Hofer T, Kuettel C, Claus C, Thom J, Herter S, Georges G, Korfi K, Lechmann M, Eigenmann MJ, Marbach D, Jamois C, Lechner K, Krishnan SM, Gaillard B, Marinho J, Kronenberg S, Kunz L, Wilson S, Briner S, Gebhardt S, Varol A, Appelt B, Nicolini V, Speziale D, Bez M, Bommer E, Eckmann J, Hage C, Limani F, Jenni S, Schoenle A, Le Clech M, Vallier JP, Colombetti S, Bacac M, Gasser S, Klein C, Umana P. CD19-CD28: an affinity-optimized CD28 agonist for combination with glofitamab (CD20-TCB) as off-the-shelf immunotherapy. Blood. 2024 May 23;143(21):2152-2165. doi: 10.1182/blood.2023023381. |
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Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.clinicalstudydatarequest.com). Further details on Roche's criteria for eligible studies are available here (https://clinicalstudydatarequest.com/Study-Sponsors/Study-Sponsors-Roche.aspx). For further details on Roche's Global Policy on Sharing of Clinical Study Information and how to request access to related clinical study documents, see here (https://www.roche.com/research\_and\_development/who\_we\_are\_how\_we\_work/clinical\_trials/our\_commitment\_to\_data\_sharing.htm)
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| Glofitamab | Drug | Glofitamab will be administered through IV infusion starting with step-up dosing (2.5 mg/10 mg/30 mg) on C1D1, C1D8, and C2D1. Starting in Cycle 3, glofitamab will be given in 30 mg doses every three weeks (Q3W) with RO7443904, for up to 12 cycles (Cycle = 21 days). |
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| Obinutuzumab | Drug | Obinutuzumab will be administered once through IV infusion, at a 1 g dose in Cycle 1, on either Day -7, -4, or -3 (C1D-7, C1D-4, C1D-3). |
|
| Tocilizumab | Drug | Tocilizumab will be administered as necessary to treat cytokine release syndrome (CRS). |
|
|
| Up to 9 months |
| Volume of distribution (Vd) of RO7443904 | Up to 9 months |
| Half-life (t1/2) of RO7443904 | Up to 9 months |
| Percentage of Participants with RO7443904 anti-drug antibodies (ADAs) during the study relative to the prevalence of ADA at baseline | Up to 9 months |
| Time to maximum concentration (Tmax) of RO7443904 | Up to 9 months |
| Cleveland |
| Ohio |
| 44195 |
| United States |
| University of Pennsylvania | Philadelphia | Pennsylvania | 19104 | United States |
| Peter MacCallum Cancer Centre; Department of Haematology | Melbourne | Victoria | 3002 | Australia |
| Rigshospitalet; Hæmatologisk Klinik, Klinisk Afprøvnings Team KAT | København Ø | 2100 | Denmark |
| CHRU Lille - Hôpital Claude Huriez; Service des Maladies du Sang | Lille | 59037 | France |
| ASST PAPA GIOVANNI XXIII; Ematologia | Bergamo | Lombardy | 24127 | Italy |
| Istituto Clinico Humanitas;U.O. Oncologia Medica Ed Ematologia | Rozzano | Lombardy | 20089 | Italy |
| Leicester Royal Infirmary; Dept of Haematology | Leicester | LE1 5WW | 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 |
| C543332 | obinutuzumab |
| C502936 | tocilizumab |
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