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| ID | Type | Description | Link |
|---|---|---|---|
| VLS-101-0001 | Other Identifier | VelosBio |
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The purpose of this study is to evaluate the safety, pharmacokinetics, immunogenicity, and efficacy of zilovertamab vedotin given intravenously (IV) across a range of dose levels in participants with previously treated hematological cancers including acute lymphocytic leukemia (ALL), acute myeloid leukemia (AML), Burkitt lymphoma (BL), chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), lymphoplasmacytoid lymphoma/Waldenström macroglobulinemia (LPL/WM), mantle cell lymphoma (MCL), marginal zone lymphoma (MZL), Richter transformation lymphoma (RTL), and T-cell non-Hodgkin lymphoma (NHL).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Zilovertamab vedotin Schedule 1: Q1/3W | Experimental | Participants will be administered escalating doses of zilovertamab vedotin at 0.50, 1.00, 1.50, 2.25, 2.50, 2.75, and 3.00 mg/kg IV on Day 1 of repeated 21-day cycles (Q1/3W). |
|
| Zilovertamab vedotin Schedule 2: Q2/3W | Experimental | Participants will be administered escalating doses of zilovertamab vedotin at 0.75, 1.00, 1.25, 1.50, 1.75, 2.00, and 2.25 mg/kg IV on Day 1 and 8 of repeated 21-day cycles (Q2/3W). |
|
| Zilovertamab vedotin Schedule 3: Q3/4W | Experimental | Participants will be administered escalating doses of zilovertamab vedotin at 0.75, 1.00, 1.25, 1.50, 1.75, 2.00, and 2.25 mg/kg IV on Day 1, 8, and 15 of repeated 21-day cycles (Q3/4W). |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Zilovertamab vedotin | Drug | Zilovertamab vedotin administered via IV infusion per Schedule 1, 2, or 3 according to participant allocation. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Maximum tolerated dose (MTD) of zilovertamab vedotin | Participants will receive zilovertamab vedotin according to Schedule 1, 2, or 3. The MTD will be determined by the number of participants who experience a dose limiting toxicity (DLT). The MTD will be defined as the highest tested dose level at which ≥6 participants have been treated and which is associated with a Cycle 1 DLT in ≤17% of the participants. | Cycle 1 (Up to 21 Days) |
| Recommended Dosing Regimen (RDR) | Selection of the RDR will be based on consideration of short- and long-term safety information together with available pharmacokinetic, pharmacodynamic, and efficacy data. The RDR may be the MTD or may be a lower dose within the tolerable dose range. | Cycle 1 (Up to 21 Days) |
| Measure | Description | Time Frame |
|---|---|---|
| Average number of zilovertamab vedotin infusions administered | Zilovertamab vedotin drug administration will be assessed by prescribing records and the average number of zilovertamab vedotin infusions administered will be determined. | Up to 5 months |
| Number of participants with a treatment-emergent adverse event (TEAE) |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Medical Director | Merck Sharp & Dohme LLC | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| City of Hope ( Site 0010) | Duarte | California | 91010 | United States | ||
| University of California - San Diego ( Site 0003) |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 38319241 | Result | Wang ML, Barrientos JC, Furman RR, Mei M, Barr PM, Choi MY, de Vos S, Kallam A, Patel K, Kipps TJ, Rule S, Flanders K, Jessen KA, Ren H, Riebling PC, Graham P, King L, Thurston AW, Sun M, Schmidt EM, Lannutti BJ, Johnson DM, Miller LL, Spurgeon SE. Zilovertamab Vedotin Targeting of ROR1 as Therapy for Lymphoid Cancers. NEJM Evid. 2022 Jan;1(1):EVIDoa2100001. doi: 10.1056/EVIDoa2100001. Epub 2021 Oct 12. | |
| 34398557 |
| Label | URL |
|---|---|
| Merck Clinical Trials Information | View source |
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Cohorts of 3 to 6 subjects will be sequentially enrolled at progressively higher dose levels within each dose schedule of zilovertamab vedotin using a 3+3 dose-escalation design.
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An AE is any untoward medical occurrence in a participant administered a medicinal product; the event does not necessarily have a causal relationship with study drug administration or usage. Laboratory abnormalities, vital sign/oxygen saturation abnormalities, and adverse electrocardiogram (ECG) findings will also be recorded as AEs. A TEAE is defined as an AE that occurs or worsens in the period from the first dose of study drug administration to 30 days after the final dose of study drug administration. The number of participants with a TEAE will be reported for each arm. |
| Up to approximately 3.5 years |
| Number of participants with a DLT | A DLT is defined as a protocol pre-specified TEAE that occurs in Cycle 1 of zilovertamab vedotin therapy and is considered drug-related. Failure to recover to baseline by ≥21 days from the last dose of study drug in the current cycle due to a drug-related TEAE is also considered a DLT. The number of participants with a DLT will be reported for each arm. | Cycle 1 (Up to 21 Days) |
| Number of participants with a serious adverse event (SAE) | An SAE is defined as an untoward medical occurrence that results in any of the following outcomes: death, life-threatening situation, in-patient hospitalization or prolongation of existing hospitalization, persistent or significant disability/incapacity, congenital anomaly/birth defect, or other medically significant event. | Up to approximately 3.5 years |
| Number of participants with an adverse event of special interest (AESI) | Prespecified AESIs for this study will include: Grade ≥3 infusion reactions, tumor lysis syndrome (TLS) of any grade, and Grade ≥3 peripheral neuropathy. The number of participants with an AESI will be reported for each arm. | Up to approximately 3.5 years |
| Number of participants that discontinue study treatment due to an AE | An AE is any untoward medical occurrence in a participant administered a medicinal product; the event does not necessarily have a causal relationship with study drug administration or usage. The number of participants that discontinue study treatment due to an AE will be reported for each arm. | Up to approximately 3.5 years |
| Number of participants that use supportive care or concomitant medications | The number of participants that use supportive care or concomitant medications will be reported for each arm. | Up to approximately 3.5 years |
| Plasma concentration of zilovertamab vedotin | Plasma concentration of zilovertamab vedotin will be reported for each arm. | Cycle 1 Day 1, 2, 3, 8, 15: predose, end of infusion (up to 4 hours); Day 1, Day 8 (Schedule 2, 3), Day 15 (Schedule 3) of Cycles 2 through end of therapy (up to ~3.5 years): predose, end of infusion |
| Plasma concentration of total UC-961 antibody | Plasma concentration of total UC-961 antibody will be reported for each arm. | Cycle 1 Day 1, 2, 3, 8, 15: predose, end of infusion (up to 4 hours); Day 1, Day 8 (Schedule 2, 3), Day 15 (Schedule 3) of Cycles 2 through end of therapy (up to ~3.5 years): predose, end of infusion |
| Plasma concentration of monomethyl auristatin E (MMAE) | Plasma concentration of MMAE will be reported for each arm. | Cycle 1 Day 1, 2, 3, 8, 15: predose, end of infusion (up to 4 hours); Day 1, Day 8 (Schedule 2, 3), Day 15 (Schedule 3) of Cycles 2 through end of therapy (up to ~3.5 years): predose, end of infusion |
| Maximum plasma concentration (Cmax) of zilovertamab vedotin | Blood samples collected predose and at multiple timepoints postdose will be used to determine Cmax of zilovertamab vedotin. | Cycle 1 Day 1, 2, 3, 8, 15: predose, end of infusion (up to 4 hours); Day 1, Day 8 (Schedule 2, 3), Day 15 (Schedule 3) of Cycles 2 through end of therapy (up to ~3.5 years): predose, end of infusion |
| Time to maximum plasma concentration (Tmax) of zilovertamab vedotin | Blood samples collected predose and at multiple timepoints postdose will be used to determine Tmax of zilovertamab vedotin. | Cycle 1 Day 1, 2, 3, 8, 15: predose, end of infusion (up to 4 hours); Day 1, Day 8 (Schedule 2, 3), Day 15 (Schedule 3) of Cycles 2 through end of therapy (up to ~3.5 years): predose, end of infusion |
| Area under the plasma concentration time curve (AUC) of zilovertamab vedotin | Blood samples collected predose and at multiple timepoints postdose will be used to determine AUC of zilovertamab vedotin. | Cycle 1 Day 1, 2, 3, 8, 15: predose, end of infusion (up to 4 hours); Day 1, Day 8 (Schedule 2, 3), Day 15 (Schedule 3) of Cycles 2 through end of therapy (up to ~3.5 years): predose, end of infusion |
| Volume of distribution (Vd) of zilovertamab vedotin | Blood samples collected predose and at multiple timepoints postdose will be used to determine Vd of zilovertamab vedotin. | Cycle 1 Day 1, 2, 3, 8, 15: predose, end of infusion (up to 4 hours); Day 1, Day 8 (Schedule 2, 3), Day 15 (Schedule 3) of Cycles 2 through end of therapy (up to ~3.5 years): predose, end of infusion |
| Clearance (CL) of zilovertamab vedotin | Blood samples collected predose and at multiple timepoints postdose will be used to determine CL of zilovertamab vedotin. | Cycle 1 Day 1, 2, 3, 8, 15: predose, end of infusion (up to 4 hours); Day 1, Day 8 (Schedule 2, 3), Day 15 (Schedule 3) of Cycles 2 through end of therapy (up to ~3.5 years): predose, end of infusion |
| Apparent terminal half-life (t½) of plasma concentration of zilovertamab vedotin | Blood samples collected predose and at multiple timepoints postdose will be used to determine t1/2 of plasma concentration of zilovertamab vedotin. | Cycle 1 Day 1, 2, 3, 8, 15: predose, end of infusion (up to 4 hours); Day 1, Day 8 (Schedule 2, 3), Day 15 (Schedule 3) of Cycles 2 through end of therapy (up to ~3.5 years): predose, end of infusion |
| Cmax of total UC-961 antibody | Blood samples collected predose and at multiple timepoints postdose will be used to determine Cmax of total UC-961 antibody. | Cycle 1 Day 1, 2, 3, 8, 15: predose, end of infusion (up to 4 hours); Day 1, Day 8 (Schedule 2, 3), Day 15 (Schedule 3) of Cycles 2 through end of therapy (up to ~3.5 years): predose, end of infusion |
| Tmax of total UC-961 antibody | Blood samples collected predose and at multiple timepoints postdose will be used to determine Tmax of total UC-961 antibody. | Cycle 1 Day 1, 2, 3, 8, 15: predose, end of infusion (up to 4 hours); Day 1, Day 8 (Schedule 2, 3), Day 15 (Schedule 3) of Cycles 2 through end of therapy (up to ~3.5 years): predose, end of infusion |
| AUC of total UC-961 antibody | Blood samples collected predose and at multiple timepoints postdose will be used to determine AUC of total UC-961 antibody. | Cycle 1 Day 1, 2, 3, 8, 15: predose, end of infusion (up to 4 hours); Day 1, Day 8 (Schedule 2, 3), Day 15 (Schedule 3) of Cycles 2 through end of therapy (up to ~3.5 years): predose, end of infusion |
| Vd of total UC-961 antibody | Blood samples collected predose and at multiple timepoints postdose will be used to determine Vd of total UC-961 antibody. | Cycle 1 Day 1, 2, 3, 8, 15: predose, end of infusion (up to 4 hours); Day 1, Day 8 (Schedule 2, 3), Day 15 (Schedule 3) of Cycles 2 through end of therapy (up to ~3.5 years): predose, end of infusion |
| CL of total UC-961 antibody | Blood samples collected predose and at multiple timepoints postdose will be used to determine CL of total UC-961 antibody. | Cycle 1 Day 1, 2, 3, 8, 15: predose, end of infusion (up to 4 hours); Day 1, Day 8 (Schedule 2, 3), Day 15 (Schedule 3) of Cycles 2 through end of therapy (up to ~3.5 years): predose, end of infusion |
| t1/2 of plasma concentration of total UC-961 antibody | Blood samples collected predose and at multiple timepoints postdose will be used to determine t1/2 of plasma concentration of total UC-961 antibody. | Cycle 1 Day 1, 2, 3, 8, 15: predose, end of infusion (up to 4 hours); Day 1, Day 8 (Schedule 2, 3), Day 15 (Schedule 3) of Cycles 2 through end of therapy (up to ~3.5 years): predose, end of infusion |
| Cmax of MMAE | Blood samples collected predose and at multiple timepoints postdose will be used to determine Cmax of MMAE. | Cycle 1 Day 1, 2, 3, 8, 15: predose, end of infusion (up to 4 hours); Day 1, Day 8 (Schedule 2, 3), Day 15 (Schedule 3) of Cycles 2 through end of therapy (up to ~3.5 years): predose, end of infusion |
| Tmax of MMAE | Blood samples collected predose and at multiple timepoints postdose will be used to determine Tmax of MMAE. | Cycle 1 Day 1, 2, 3, 8, 15: predose, end of infusion (up to 4 hours); Day 1, Day 8 (Schedule 2, 3), Day 15 (Schedule 3) of Cycles 2 through end of therapy (up to ~3.5 years): predose, end of infusion |
| AUC of MMAE | Blood samples collected predose and at multiple timepoints postdose will be used to determine AUC of MMAE. | Cycle 1 Day 1, 2, 3, 8, 15: predose, end of infusion (up to 4 hours); Day 1, Day 8 (Schedule 2, 3), Day 15 (Schedule 3) of Cycles 2 through end of therapy (up to ~3.5 years): predose, end of infusion |
| Vd of MMAE | Blood samples collected predose and at multiple timepoints postdose will be used to determine Vd of MMAE. | Cycle 1 Day 1, 2, 3, 8, 15: predose, end of infusion (up to 4 hours); Day 1, Day 8 (Schedule 2, 3), Day 15 (Schedule 3) of Cycles 2 through end of therapy (up to ~3.5 years): predose, end of infusion |
| CL of MMAE | Blood samples collected predose and at multiple timepoints postdose will be used to determine CL of MMAE. | Cycle 1 Day 1, 2, 3, 8, 15: predose, end of infusion (up to 4 hours); Day 1, Day 8 (Schedule 2, 3), Day 15 (Schedule 3) of Cycles 2 through end of therapy (up to ~3.5 years): predose, end of infusion |
| t1/2 of plasma concentration of MMAE | Blood samples collected predose and at multiple timepoints postdose will be used to determine t1/2 of plasma concentration of MMAE. | Cycle 1 Day 1, 2, 3, 8, 15: predose, end of infusion (up to 4 hours); Day 1, Day 8 (Schedule 2, 3), Day 15 (Schedule 3) of Cycles 2 through end of therapy (up to ~3.5 years): predose, end of infusion |
| Number of participants with zilovertamab vedotin-reactive antibodies | Number of participants with zilovertamab vedotin-reactive antibodies will be assessed. | Day 1 of Cycles 1 through end of therapy (up to approximately 3.5 years): predose and end of infusion (up to ~30 minutes) |
| Overall Response (OR) | OR will be defined by achievement of the following outcomes as indicated by disease type: CLL/SLL: Complete response (CR: disappearance of detectable disease per Cheson 2012 criteria), CR with incomplete blood count recovery (CRi: CR with ≥1 additional change in absolute neutrophil count, platelet count, or hemoglobin), partial response (PR: no evidence of new disease per Cheson 2012 criteria), or PR with lymphocytosis (PR except lack of decrease in peripheral blood absolute lymphocyte count); NHL: CR (disappearance of all detectable disease per Cheson 2014 criteria) or PR (≥50% decrease in the sum of the product of diameters of the index nodal and extranodal lesions); LPL/WM: CR, very good PR (CR with ≥90% decrease in M protein), PR, or minor response (criteria for PR or stable disease met per Cheson 2014); ALL: (CR, CRi, unconfirmed CR, or PR per National Comprehensive Cancer Network criteria); AML (CR, CRi, morphologic leukemia-free state [MLFS], or PR per Cheson 2003 criteria). | Up to approximately 3.5 years |
| Complete Response without measurable residual disease (CRMRD-) | CRMRD- is defined as the achievement of ≤1 × 10^-4 malignant cells in bone marrow (as assessed by flow cytometry) in a participant who meets all other criteria for CR. | Up to approximately 3.5 years |
| Percent change from baseline in tumor dimension | Percent change in tumor dimensions is defined as the percent change from baseline in the sum of the products of the diameters (SPD) of index lesions. | Up to approximately 3.5 years |
| Time to Response (TTR) | TTR is defined as the interval from the start of study therapy to the first documentation of an objective response. | Up to approximately 3.5 years |
| Duration of Response (DOR) | DOR is defined as the interval from the first documentation of objective response to the earlier of the first documentation of disease progression/relapse or death from any cause. | Up to approximately 3.5 years |
| Progression free survival (PFS) | PFS is defined as the interval from the start of study therapy to the earlier of the first documentation of disease progression/relapse or death from any cause. | Up to approximately 3.5 years |
| Time to Treatment Failure (TTF) | TTF failure is defined as the interval from start of study therapy to the earliest of the first documentation of disease progression/relapse, treatment failure (for participants with ALL or AML), the permanent cessation of study drug due to an AE, or death from any cause. | Up to approximately 3.5 years |
| Overall Survival (OS) | OS is defined as the interval from the start of study therapy to death from any cause. | Up to approximately 3.5 years |
| La Jolla |
| California |
| 92093 |
| United States |
| UCLA Hematology & Oncology ( Site 0007) | Los Angeles | California | 90095 | United States |
| University of Nebraska Medical Center ( Site 0006) | Omaha | Nebraska | 68198-5331 | United States |
| Northwell Health ( Site 0009) | New Hyde Park | New York | 11042 | United States |
| Weill Cornell Medical College ( Site 0005) | New York | New York | 10021 | United States |
| Memorial Sloan Kettering Cancer Center ( Site 0014) | New York | New York | 10065 | United States |
| University of Rochester ( Site 0008) | Rochester | New York | 14642 | United States |
| Memorial Sloan-Kettering Cancer Center ( Site 0019) | Uniondale | New York | 11553 | United States |
| Oregon Health & Science University ( Site 0004) | Portland | Oregon | 97239 | United States |
| MD Anderson Cancer Center ( Site 0001) | Houston | Texas | 77030 | United States |
| MD Anderson Cancer Center ( Site 0011) | Houston | Texas | 77030 | United States |
| University of Virginia Cancer Center ( Site 0012) | Charlottesville | Virginia | 22908 | United States |
| Swedish Medical Center ( Site 0002) | Seattle | Washington | 98104 | United States |
| Derived |
| Kipps TJ. Mining the Microenvironment for Therapeutic Targets in Chronic Lymphocytic Leukemia. Cancer J. 2021 Jul-Aug 01;27(4):306-313. doi: 10.1097/PPO.0000000000000536. |
| ID | Term |
|---|---|
| D015451 | Leukemia, Lymphocytic, Chronic, B-Cell |
| D020522 | Lymphoma, Mantle-Cell |
| D008224 | Lymphoma, Follicular |
| D018442 | Lymphoma, B-Cell, Marginal Zone |
| D016403 | Lymphoma, Large B-Cell, Diffuse |
| D002051 | Burkitt Lymphoma |
| D008258 | Waldenstrom Macroglobulinemia |
| D016399 | Lymphoma, T-Cell |
| D054198 | Precursor Cell Lymphoblastic Leukemia-Lymphoma |
| D015470 | Leukemia, Myeloid, Acute |
| D008223 | Lymphoma |
| D008228 | Lymphoma, Non-Hodgkin |
| D015448 | Leukemia, B-Cell |
| D007945 | Leukemia, Lymphoid |
| D007938 | Leukemia |
| ID | Term |
|---|---|
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D008232 | Lymphoproliferative Disorders |
| D008206 | Lymphatic Diseases |
| D007160 | Immunoproliferative Disorders |
| D007154 | Immune System Diseases |
| D002908 | Chronic Disease |
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D016393 | Lymphoma, B-Cell |
| D020031 | Epstein-Barr Virus Infections |
| D006566 | Herpesviridae Infections |
| D004266 | DNA Virus Infections |
| D014777 | Virus Diseases |
| D007239 | Infections |
| D014412 | Tumor Virus Infections |
| D054219 | Neoplasms, Plasma Cell |
| D020141 | Hemostatic Disorders |
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
| D010265 | Paraproteinemias |
| D001796 | Blood Protein Disorders |
| D006474 | Hemorrhagic Disorders |
| D007951 | Leukemia, Myeloid |
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