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

Phase 1

Terminated

• Conditions: Multiple Myeloma (MM)
• Interventions: Biological: WVT078; Drug: WHG626

• Registration Number: NCT04123418
• Lead Sponsor: Novartis Pharmaceuticals

Brief Summary

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

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.

Study Timeline

• Study First Submitted: 2019-10-02
• Study First Submitted QC: 2019-10-09
• Study First Posted: 2019-10-10
• Study Start: 2019-12-05
• Primary Completion: 2024-12-02
• Study Completion: 2024-12-02
• Status Verified: 2025-01
• Last Update Submitted: 2025-01-07
• Last Update Posted: 2025-01-09

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 56

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)

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
WVT078 in Multiple Myeloma (MM) patients	WVT078	Dose escalation study to determine Maximum Tolerated Dose (MTD)/ Recommended Dose (RD) in adult patients with relapsed and/or refractory Multiple Myeloma (MM)
WVT078 in combination with WHG626 in Multiple Myeloma (MM) patients	WHG626	Dose escalation study to determine Maximum Tolerated Dose (MTD)/ Recommended Dose (RD) in adult patients with relapsed and/or refractory Multiple Myeloma (MM)
WVT078 in combination with WHG626 in Multiple Myeloma (MM) patients	WVT078	Dose escalation study to determine Maximum Tolerated Dose (MTD)/ Recommended Dose (RD) in adult patients with relapsed and/or refractory Multiple Myeloma (MM)

Primary Outcome Measures

Name	Time	Method
Incidence of dose limiting toxicity (DLTs) in Cycle 1	28 days (first cycle)	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
Frequency of dose interruptions	Up to 28 months	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
Frequency of discontinuations	up to 28 months	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
Incidence and severity of AEs and SAEs, including changes in laboratory values, vital signs, ECGs, and CRS/immune-mediated reactions	Up to 31 months	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
Frequency of dose reductions	up to 28 months	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

Secondary Outcome Measures

Name	Time	Method
Tmax of WVT078 derived from serum concentrations	Up to 28 months
AUC of WVT078 derived from serum concentrations	Up to 28 months
Cmin 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
Duration of Response (DOR)	Up to 36 months	Response assessment per International Myeloma Working Group (IMWG) criteria
Progresson Free Survival (PFS)	Up to 36 months	Response assessment per International Myeloma Working Group (IMWG) criteria
Cmax of WVT078 derived from serum concentrations	Up to 28 months
AUC 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
Best Overall Response (BOR)	Up to 36 months	Response assessment per International Myeloma Working Group (IMWG) criteria
T1/2 of WVT078 derived from serum concentrations	Up to 28 months
AUC 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
Tmax of WHG626 derived from plasma concentrations	Up to 28 months
Cmax of WHG626 derived from plasma concentrations	Up to 28 months
T1/2 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 WHG626 derived from plasma concentrations	Up to 28 months
Tmax of GWQ573 (the active metabolite of WHG626) derived from plasma concentrations	Up to 28 months

Trial Locations

Locations (4)

Emory University School of Medicine-Winship Cancer Institute; 🇺🇸 Atlanta, Georgia, United States

University Of Wisconsin; 🇺🇸 Madison, Wisconsin, United States

Medical College of Wisconsin; 🇺🇸 Milwaukee, Wisconsin, United States

Novartis Investigative Site; 🇪🇸 Barcelona, Spain