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| ID | Type | Description | Link |
|---|---|---|---|
| 2018-001041-13 | EudraCT Number | ||
| 2022-502053-34-00 | Other Identifier | EU CT Number |
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This is a phase I, multicenter, open-label, dose-escalation study of cevostamab administered as a single agent by IV infusion to participants with relapsed or refractory multiple myeloma (R/R MM).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Arm A: Single Step Dose Escalation for Cevostamab | Experimental | Study drug will be administered intravenously on a 21-day cycle. The step-up dose will be given on Cycle 1 Day 1 and the target dose will be given on C1D8. Subsequently the target dose will be administered on Day 1 of each 21-day cycle. |
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| Arm B: Double Step Dose Escalation for Cevostamab | Experimental | In Cycle 1, participants will receive 2 step-up doses and a target dose. The step-up dose will be given on Cycle 1 Day 1 and C1D8. The target dose will be given on C1D15. Subsequently the target dose will be administered on Day 1 of each 21-day cycle. |
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| Arm C: Single Step Dose Expansion for Cevostamab | Experimental | The single step dose expansion stage of the study may use the dosing and assessment schedule from the single dose escalation arm in Cycle 1, based on data from Arm A. |
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| Arm D: Double Step Dose Expansion for Cevostamab | Experimental | The double step dose expansion stage of the study may use the dosing and assessment schedule from the double step dose escalation arm in Cycle 1, based on data from Arm B. |
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| Arm E: Expansion Phase for Tocilizumab Pretreatment |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Cevostamab | Drug | Cevostamab will be administered intravenously on a 21-day cycle, up to a total of 17 cycles. |
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| Measure | Description | Time Frame |
|---|---|---|
| Percentage of Participants with Adverse Events (AEs) | An AE is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure. | Up to approximately 8 years |
| Percentage of Participants With Dose-Limiting Toxicities (DLTs) | Dose-Limiting Toxicities (DLTs) will be reported according to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI CTCAE v4.0), except for Cytokine release syndrome (CRS), which will be graded according to the American Society of Transplantation and Cellular Therapy (ASTCT) Consensus Grading for Cytokine Release Syndrome. | Up to approximately 8 years |
| Arms E and J Only: Incidence and Severity of Cytokine-release Syndrome (CRS) Following Tocilizumab Premedication Followed by Treatment with Cevostamab | Cytokine release syndrome was recorded as an AE that generally occurs >30 minutes after the start of Cevostamab administration and at any time afterward in a given cycle. | Up to approximately 8 years |
| Measure | Description | Time Frame |
|---|---|---|
| Area Under the Concentration-Time Curve (AUC) of Cevostamab | Defined as the total exposure of study drug. | Up to approximately 8 years |
| AUC of Tocilizumab | Defined as the total exposure of study drug. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Clinical Trials | Genentech, Inc. | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Alabama at Birmingham | Birmingham | Alabama | 35249 | United States | ||
| Mayo Clinic Hospital - Arizona |
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All participants will receive a single dose of tocilizumab intravenously. An additional dose of tocilizumab may be instituted as premedication for subsequent Cycle 1 dose(s) of cevostamab and Cycle 1 cevostamab doses for other treatment arms. |
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| Arm F: Single Step Dose Expansion for Cevostamab | Experimental | The single step dose expansion stage of the study may use the dosing and assessment schedule from the single dose escalation arm in Cycle 1, based on data from Arm A. |
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| Arm G: Double Step Dose Expansion for Cevostamab | Experimental | The double step dose expansion stage of the study may use the dosing and assessment schedule from the double step dose escalation arm in Cycle 1, based on data from Arm B. |
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| Arm H: Triple Step Dose Escalation for Cevostamab | Experimental | In Cycle 1, participants will receive 3 step-up doses and a target dose. The doses will be given on Cycle 1 Days 1, 2-4, 8, and 9-11. Subsequently the target dose will be administered on Day 1 of each 21-day cycle. |
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| Arm I: Triple Step Dose Expansion for Cevostamab | Experimental | The triple step dose expansion stage of the study may use the dosing and assessment schedule from the triple step dose escalation arm in Cycle 1, based on data from Arm H. |
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| Arm J: Expansion Phase for Tocilizumab Pretreatment | Experimental | All participants will receive a single dose of tocilizumab intravenously. An additional dose of tocilizumab may be instituted as premedication for subsequent Cycle 1 dose(s) of cevostamab and Cycle 1 cevostamab doses for other treatment arms. |
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| Arm K: Compressed Double Step Dose Expansion for Cevostamab | Experimental | In Cycle 1, participants will receive 2 step-up doses and a target dose. The doses will be given on Cycle 1 Days 1, 4, and 8. Subsequently the target dose will be administered on Day 1 of each 21-day cycle. |
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| Tocilizumab | Drug | Tocilizumab will be administered as premedication during Cycle 1. |
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| Up to approximately 8 years |
| Maximum Observed Serum Concentration (Cmax) of Cevostamab | Defined as the maximum observed serum concentration of study drug. | Up to approximately 8 years |
| Cmax of Tocilizumab | Defined as the maximum observed serum concentration of study drug. | Up to approximately 8 years |
| Minimum Observed Serum Concentration (Cmin) of Cevostamab | Defined as the minimum observed serum concentration of study drug. | Up to approximately 8 years |
| Cmin of Tocilizumab | Defined as the minimum observed serum concentration of study drug. | Up to approximately 8 years |
| Clearance (CL) of Cevostamab | Defined as the volume of plasma cleared of the drug per unit time. | Up to approximately 8 years |
| CL of Tocilizumab | Defined as the volume of plasma cleared of the drug per unit time. | Up to approximately 8 years |
| Volume of Distribution at Steady State (Vdss) of Cevostamab | Defined as the actual blood and tissue volume into which a drug is distributed and the relative binding of drug to protein in these spaces. | Up to approximately 8 years |
| Vdss of Tocilizumab | Defined as the actual blood and tissue volume into which a drug is distributed and the relative binding of drug to protein in these spaces. | Up to approximately 8 years |
| Serum Concentration of Cevostamab | Up to approximately 8 years |
| Serum Concentration of Tocilizumab | Up to approximately 8 years |
| Objective Response Rate (ORR) | ORR is defined as percentage of participants with stringent complete response (sCR), complete response (CR), very good partial response (VGPR) or partial response (PR) . sCR is defined as CR (as defined below), plus: Normal FLC ratio and absence of clonal cells in bone marrow (BM) by immunohistochemistry (kappa/lambda ratio </=4:1 or >/=1:2 for kappa and lambda participants, respectively after counting >/=100 plasma cells). CR is defined as no evidence of initial monoclonal protein isotype(s) on immunofixation of the serum and urine, disappearance of any soft tissue plasmacytomas, and </= 5% plasma cells in BM. VGPR is defined as Serum and urine M-protein detectable by immunofixation but not on electrophoresis; or >/=90% reduction in serum M-protein plus urine M-protein level <100 milligrams (mg)/24 hr. PR is defined as >/= 50% reduction of serum M-protein and reduction in 24-hour urine M-protein by >/= 90% or to < 200 mg/24 hours. | Up to approximately 8 years |
| Duration of Response | Time from first occurrence of ORR (defined previously) to disease progression (PD) or death from any cause. PD: increase of >/=25% from lowest response value in one of the following: serum M-protein (absolute increase >/=0.5 grams per deciliter (g/dL); serum M-protein increase >/=1g/dL, if lowest M component was >/=5g/dL; urine M-protein (absolute increase >/=200 mg/24 hours); no measurable serum and urine M-protein levels: difference between involved and uninvolved free light chain (FLC) levels (absolute increase >10 mg/dL); no measurable serum and urine M-protein levels and no measurable disease by FLC: BM plasma cell % irrespective of baseline status (absolute % >/=10%); new lesion(s) >/=50% increase from lowest point in sum of the products of diameters of > 1 lesion, or >/=50% increase in longest diameter of a previous lesion >1 centimeter (cm) in short axis; >/=50% increase in circulating plasma cells (minimum 200 cells per microliter) if only measure of disease. | Up to approximately 8 years |
| Change from Baseline in the Presence Anti-Drug Antibodies (ADAs) | To evaluate the immune response to the study drug. | Up to approximately 8 years |
| Scottsdale |
| Arizona |
| 85259 |
| United States |
| City of Hope | Duarte | California | 91010 | United States |
| University of Colorado Denver | Aurora | Colorado | 80045 | United States |
| Dana Farber Cancer Institute | Boston | Massachusetts | 02215 | United States |
| Memorial Sloan Kettering | New York | New York | 10065 | United States |
| Mount Sinai Hospital | New York | New York | 10128 | United States |
| University of Pennsylvania | Philadelphia | Pennsylvania | 19104 | United States |
| Tennessee Oncology - Nashville | Nashville | Tennessee | 37203 | United States |
| The University of Texas MD Anderson Cancer Center | Houston | Texas | 77030-4009 | United States |
| Peter MacCallum Cancer Center | East Melbourne | Victoria | 3022 | Australia |
| Alfred Hospital | Melbourne | Victoria | 3004 | Australia |
| University of Calgary Cumming School of Medicine | Calgary | Alberta | T2N 4N2 | Canada |
| Princess Margaret Cancer Center | Toronto | Ontario | M5G 2M9 | Canada |
| Jewish General Hospital | Montreal | Quebec | H3T 1E2 | Canada |
| Clinica Universidad de Navarra | Pamplona/iruña | Navarre | 31008 | Spain |
| Hospital Clinico Universitario de Salamanca | Salamanca | 37007 | Spain |
| ID | Term |
|---|---|
| D009101 | Multiple Myeloma |
| ID | Term |
|---|---|
| D054219 | Neoplasms, Plasma Cell |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D020141 | Hemostatic Disorders |
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
| D010265 | Paraproteinemias |
| D001796 | Blood Protein Disorders |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D006474 | Hemorrhagic Disorders |
| D008232 | Lymphoproliferative Disorders |
| D007160 | Immunoproliferative Disorders |
| D007154 | Immune System Diseases |
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| ID | Term |
|---|---|
| C502936 | tocilizumab |
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