A proof-of-concept study to learn whether linvoseltamab can eliminate abnormal plasma cells that may lead to multiple myeloma in adult patients with High-Risk Monoclonal Gammopathy of Undetermined Significance or Non-High-Risk Smoldering Multiple Myeloma
- Conditions
- High-Risk Monoclonal Gammopathy of Undetermined Significance; Non-High-Risk Smoldering Multiple Myeloma
- Interventions
- Registration Number
- 2023-505242-25-00
- Lead Sponsor
- Regeneron Pharmaceuticals Inc.
- Brief Summary
Safety Run-In (Part 1): To evaluate the safety and tolerability of linvoseltamab in ascending dose-level cohorts and select the highest dose level for investigation in the expansion part.
Expansion (Part 2): To evaluate the ability of linvoseltamab to induce complete responses (CR) by dosing regimen.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised, recruiting
- Sex
- Not specified
- Target Recruitment
- 82
HR-MGUS or NHR-SMM as defined in the protocol
Eastern Cooperative Oncology Group (ECOG) performance status ≤1
Adequate hematologic and hepatic function, as described in the protocol
Estimated glomerular filtration rate (GFR) ≥30 mL/min/1.73 m2 by the modification of diet in renal disease (MDRD) equation.
NOTE: Other protocol defined inclusion criteria apply
High-risk SMM according to risk stratification models as defined in the protocol.
Evidence of any of myeloma-defining events, as described in the protocol
Diagnosis of systemic light-chain amyloidosis, Waldenström macroglobulinemia (lymphoplasmacytic lymphoma), solitary plasmacytoma, or symptomatic MM
Clinically significant cardiac or vascular disease within 3 months of study enrollment, as described in the protocol
Any infection requiring hospitalization or treatment with IV anti-infectives within 28 days of the first dose of linvoseltamab
Uncontrolled human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV) infection; or other uncontrolled infection or unexplained signs of infection.
NOTE: Other protocol defined exclusion criteria apply
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- Not specified
- Arm && Interventions
Group Intervention Description Expansion (Part 2) - Dose regimen 1 Linvoseltamab Participants will be randomized in a 1:1:1:1 ratio across 4 dosing regimens Safety Run-In (Part 1) Linvoseltamab Sequential groups of participants will be enrolled to assess the initial safety and tolerability of the step-up regimen leading up to the start of different full doses of linvoseltamab. Expansion (Part 2) - Dose regimen 2 Linvoseltamab Participants will be randomized in a 1:1:1:1 ratio across 4 dosing regimens Expansion (Part 2) - Dose regimen 3 Linvoseltamab Participants will be randomized in a 1:1:1:1 ratio across 4 dosing regimens Expansion (Part 2) - Dose regimen 4 Linvoseltamab Participants will be randomized in a 1:1:1:1 ratio across 4 dosing regimens
- Primary Outcome Measures
Name Time Method Part 1: Frequency of adverse events of special interest (AESI) during the safety observation period Part 1: Frequency of adverse events of special interest (AESI) during the safety observation period
Part 1: Frequency of treatment-emergent adverse events (TEAEs) during the safety observation period Part 1: Frequency of treatment-emergent adverse events (TEAEs) during the safety observation period
Part 1: Severity of TEAEs during the safety observation period Part 1: Severity of TEAEs during the safety observation period
Part 2: Achievement of complete response (CR) as determined by the investigator Part 2: Achievement of complete response (CR) as determined by the investigator
- Secondary Outcome Measures
Name Time Method Incidence of anti-drug antibodies (ADAs) to linvoseltamab over time Incidence of anti-drug antibodies (ADAs) to linvoseltamab over time
Titer of ADAs to linvoseltamab over time Titer of ADAs to linvoseltamab over time
Frequency of TEAEs Frequency of TEAEs
Severity of TEAEs Severity of TEAEs
Frequency of serious adverse events (SAEs) Frequency of serious adverse events (SAEs)
Severity of SAEs Severity of SAEs
Frequency of laboratory abnormalities Frequency of laboratory abnormalities
Severity of laboratory abnormalities Severity of laboratory abnormalities
Minimal residual disease (MRD) negativity among participants that achieve a response of CR Minimal residual disease (MRD) negativity among participants that achieve a response of CR
Sustained MRD negativity on an annual basis Sustained MRD negativity on an annual basis
Overall response of partial response (PR) or better as determined by the investigator Overall response of partial response (PR) or better as determined by the investigator
Duration of response (DOR) as determined by the investigator Duration of response (DOR) as determined by the investigator
Biochemical progression-free survival (PFS) as determined by the investigator Biochemical progression-free survival (PFS) as determined by the investigator
Concentration of linvoseltamab in serum over time Concentration of linvoseltamab in serum over time
Trial Locations
- Locations (33)
Specjalistyczny Szpital Im. Dra Alfreda Sokolowskiego
🇵🇱Walbrzych, Poland
Wojewodzkie Wielospecjalistyczne Centrum Onkologii I Traumatologii Im M.Kopernika W Lodzi
🇵🇱Lodz, Poland
Pratia S.A.
🇵🇱Cracow, Poland
Wojewodzki Szpital Zespolony Im.L.Rydygiera W Toruniu
🇵🇱Torun, Poland
Swietokrzyskie Centrum Onkologii Samodzielny Publiczny Zaklad Opieki Zdrowotnej W Kielcach
🇵🇱Kielce, Poland
Uniwersyteckie Centrum Kliniczne
🇵🇱Gdansk, Poland
Cork University Hospital
🇮🇪Cork, Ireland
Mater Misericordiae University Hospital
🇮🇪Dublin 7, Ireland
University Hospital Galway
🇮🇪Galway, Ireland
IRCCS Ospedale Policlinico San Martino
🇮🇹Genoa, Italy
Scroll for more (23 remaining)Specjalistyczny Szpital Im. Dra Alfreda Sokolowskiego🇵🇱Walbrzych, PolandAleksandra ButrymSite contact+48746489736onkocwbk@zdrowie.walbrzych.pl