Multiple Myeloma (MM)
Conditions
Keywords
Multiple Myeloma, phase 1
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.
Interventions
BIOLOGICALWVT078
WVT078 will be administered IV (intravenously) in a dose escalation schedule
DRUGWHG626
WHG626 will be administered orally in a dose escalation schedule
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 99 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| 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 |
| 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | — |
| Best Overall Response (BOR) | Up to 36 months | Response assessment per International Myeloma Working Group (IMWG) criteria |
| 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 | — |
| Tmax of WHG626 derived from plasma concentrations | 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 |
| AUC of WVT078 derived from serum concentrations | Up to 28 months | — |
| Cmax of WVT078 derived from serum concentrations | Up to 28 months | — |
Countries
Australia, Germany, Israel, Italy, Japan, Norway, Spain, United States
Outcome results
None listed