A Study of WVT078 in Patients With Multiple Myeloma (MM)

Study Overview
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Brief Summary
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The design of a phase I, open-label, dose finding study was chosen in order to establish a safe and tolerated dose of single agent WVT078 alone and in combination with WHG626 in patients relapses and/or refractory Multiple Myeloma (MM)

Detailed Description
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This first-in-human trial with WVT078 is a dose escalation study whose primary purpose is to characterize the safety, tolerability, and determine recommended dose regimen(s) of WVT078 alone and in combination with WHG626 in subjects with MM who have received two or more standard of care lines of therapy including an IMID, a proteasome inhibitor, and an anti-CD38 agent (if available) and are relapsed and/or refractory to or intolerant of each regimen. In addition, this study will assess preliminary anti-MM response of and characterize the pharmacokinetics and immunogenicity of WVT078 alone and in combination with WHG626. The results of this study will inform the future development of WVT078 alone and in combination with WHG626 as a treatment for relapsed and/or refractory MM.

Official Title
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A Phase I, Open-label, Multicenter, Study of WVT078 in Subjects With Relapsed and/or Refractory Multiple Myeloma

Conditions
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Multiple Myeloma (MM)

Intervention / Treatment
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* Biological: WVT078
* Drug: WHG626


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects who are relapsed and/or refractory to two or more regimens including an IMID, proteasome inhibitor, and an anti-CD38 agent (if available) Exclusion Criteria: Use of systemic chronic steroid therapy (>or= 10mg/day prednisone or equivalent) or any immunosuppressive therapy within 7 days of first dose of study treatment Malignant disease other than being treated on this study Active known or suspected autoimmune disease Impaired cardiac function or clinically significant cardiac disease Treatment with cytotoxic or small molecule antineoplastics or any experimental therapy within 14 days or 5 half-lives whichever is shorter Active central nervous system involvement by malignancy or presence of symptomatic CNS metasteses

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 99 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: WVT078 in Multiple Myeloma (MM) patients<br>Dose escalation study to determine Maximum Tolerated Dose (MTD)/ Recommended Dose (RD) in adult patients with relapsed and/or refractory Multiple Myeloma (MM) | Biological: WVT078<br>* WVT078 will be administered IV (intravenously) in a dose escalation schedule<br>|
| Experimental: WVT078 in combination with WHG626 in Multiple Myeloma (MM) patients<br>Dose escalation study to determine Maximum Tolerated Dose (MTD)/ Recommended Dose (RD) in adult patients with relapsed and/or refractory Multiple Myeloma (MM) | Biological: WVT078<br>* WVT078 will be administered IV (intravenously) in a dose escalation schedule<br>Drug: WHG626<br>* WHG626 will be administered orally in a dose escalation schedule<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of dose limiting toxicity (DLTs) in Cycle 1 | To characterize the safety, tolerability, and determine the recommended dose regimen(s) of WVT078 alone and in combination with WHG626 in subjects with relapsed and/or refractory MM | 28 days (first cycle) | 
| Frequency of dose interruptions | To characterize the safety, tolerability, and determine the recommended dose regimen(s) of WVT078 alone and in combination with WHG626 in subjects with relapsed and/or refractory MM | Up to 28 months | 
| Frequency of discontinuations | To characterize the safety, tolerability, and determine the recommended dose regimen(s) of WVT078 alone and in combination with WHG626 in subjects with relapsed and/or refractory MM | up to 28 months | 
| Frequency of dose reductions | To characterize the safety, tolerability, and determine the recommended dose regimen(s) of WVT078 alone and in combination with WHG626 in subjects with relapsed and/or refractory MM | up to 28 months | 
| Incidence and severity of AEs and SAEs, including changes in laboratory values, vital signs, ECGs, and CRS/immune-mediated reactions | To characterize the safety, tolerability, and determine the recommended dose regimen(s) of WVT078 alone and in combination with WHG626 in subjects with relapsed and/or refractory MM | Up to 31 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Best Overall Response (BOR) | Response assessment per International Myeloma Working Group (IMWG) criteria | Up to 36 months | 
| Duration of Response (DOR) | Response assessment per International Myeloma Working Group (IMWG) criteria | Up to 36 months | 
| Progresson Free Survival (PFS) | Response assessment per International Myeloma Working Group (IMWG) criteria | Up to 36 months | 
| AUC of WVT078 derived from serum concentrations |  | Up to 28 months | 
| Cmax of WVT078 derived from serum concentrations |  | Up to 28 months | 
| Cmin of WVT078 derived from serum concentrations |  | Up to 28 months | 
| Tmax of WVT078 derived from serum concentrations |  | Up to 28 months | 
| T1/2 of WVT078 derived from serum concentrations |  | Up to 28 months | 
| Concentration of WVT078 Anti Drug Antibodies (ADA) as measured in serum |  | Up to 28 months | 
| AUC of WHG626 derived from plasma concentrations |  | Up to 28 months | 
| Cmax of WHG626 derived from plasma concentrations |  | Up to 28 months | 
| Cmin of WHG626 derived from plasma concentrations |  | Up to 28 months | 
| Tmax of WHG626 derived from plasma concentrations |  | Up to 28 months | 
| T1/2 of WHG626 derived from plasma concentrations |  | Up to 28 months | 
| AUC of GWQ573 (the active metabolite of WHG626) derived from plasma concentrations |  | Up to 28 months | 
| Cmax of GWQ573 (the active metabolite of WHG626) derived from plasma concentrations |  | Up to 28 months | 
| Cmin of GWQ573 (the active metabolite of WHG626) devived from plasma concentrations |  | Up to 28 months | 
| Tmax of GWQ573 (the active metabolite of WHG626) derived from plasma concentrations |  | Up to 28 months | 
| T1/2 of GWQ573 (the active metabolite of WHG626) derived from plasma concentrations |  | Up to 28 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Multiple Myeloma, phase 1