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

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

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)

Study Overview

• Status: Active, not recruiting
• Conditions: Multiple Myeloma (MM)
• Intervention / Treatment: Biological: WVT078; Drug: WHG626

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 Type: Interventional
• Enrollment (Actual): 56
• Phase: Phase 1

Contacts and Locations

Study Locations

• Australia
  • Victoria
    • Prahran, Victoria, Australia, 3181
      • Novartis Investigative Site
• Germany
  • Dresden, Germany, 01307
    • Novartis Investigative Site
  • Heidelberg, Germany, 69120
    • Novartis Investigative Site
• Israel
  • Tel Aviv, Israel, 6423906
    • Novartis Investigative Site
• Italy
  • MI
    • Milano, MI, Italy, 20162
      • Novartis Investigative Site
• Japan
  • Tokyo
    • Bunkyo ku, Tokyo, Japan, 113-8677
      • Novartis Investigative Site
• Norway
  • Oslo, Norway, NO 0450
    • Novartis Investigative Site
• Spain
  • Barcelona, Spain, 08041
    • Novartis Investigative Site
  • Cantabria
    • Santander, Cantabria, Spain, 39008
      • Novartis Investigative Site
• United States
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University School of Medicine/Winship Cancer Institute .
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
      • University of Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Medical College of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 99 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: WVT078 in Multiple Myeloma (MM) patients; 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; WVT078 will be administered IV (intravenously) in a dose escalation schedule
Experimental: WVT078 in combination with WHG626 in Multiple Myeloma (MM) patients; 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; WVT078 will be administered IV (intravenously) in a dose escalation schedule; Drug: WHG626; WHG626 will be administered orally in a dose escalation schedule

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): December 5, 2019
• Primary Completion (Estimated): November 29, 2024
• Study Completion (Estimated): December 2, 2024

Study Registration Dates

• First Submitted: October 2, 2019
• First Submitted That Met QC Criteria: October 9, 2019
• First Posted (Actual): October 10, 2019

Study Record Updates

• Last Update Posted (Actual): March 15, 2024
• Last Update Submitted That Met QC Criteria: March 14, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Multiple Myeloma, phase 1
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Immunoproliferative Disorders; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Multiple Myeloma; Neoplasms, Plasma Cell
• Other Study ID Numbers: CWVT078A12101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No