Subjects with pathologically documented relapsed/ refractory multiple myeloma MedDRA version: 21.0 Level: LLT Classification code 10028228 Term: Multiple myeloma System Organ Class: 100000004864
Conditions
Interventions
Product Code: AMG-701
Pharmaceutical Form: Lyophilisate for solution for infusion
INN or Proposed INN: pavurutamab
Other descriptive name: AMG 701
Concentration unit: mg milligram(s)
Concentration typ
Sponsors
Amgen Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Subject has provided informed consent/assent prior to initiation of any study specific activities/procedures. - Age = 18 years at the time of signing the informed consent. - Multiple myeloma meeting the following criteria: - Pathologically-documented diagnosis of multiple myeloma that is relapsed or is refractory as defined by the following: - Relapsed after = 3 lines of prior therapy that must include all approved and available therapies deemed eligible by the investigator, including at a minimum of a proteasome inhibitor (PI), an immunomodulatory drug (IMiD), and a CD38-directed antibody in combination in the same line or separate lines of treatment OR refractory to PI, IMiD and CD38-directed antibody - Note: Subjects enrolled in the phase 1b AMG 701 monotherapy dose confirmation part group 2 must be relapsed or intolerant to BCMA targeting agent - Measurable disease, defined by 1 or more of the following at time of screening - a serum M protein = 0.5 g/dL measured by serum protein electrophoresis (SPEP) - urinary M protein excretion = 200 mg/24 hours - involved sFLC measurement > 10 mg/dL, provided that the sFLC ratio is abnormal as per IMWG response criteria - Eastern Cooperative Oncology Group (ECOG) Performance Status of = 2 - Life expectancy of at least 3 months as per investigator`s judgment at time of screening - Hematological function without transfusion support as follows: - absolute neutrophil count (ANC) = 1.0 x 109/L (without growth factor support) - platelet count = 50 x 109/L (without transfusions within 7 days from screening assessment) - hemoglobin = 8.0 g/dL (transfusions permitted no later than 48 hours before screening) Renal function as follows: - calculated or measured creatinine clearance = 30 mL/min using: - the Cockcroft-Gault equation OR - via 24-hour urine collection with plasma and urine creatinine concentrations Hepatic function as follows: - aspartate aminotransferase (AST) and alanine aminotransferase (ALT) = 2.5 mg/dL (>= 0.8 mmol/L) within 7 days of day 1 - A subject who does not meet this inclusion criteria may be treated with phosphate replacement therapy and re-screened up to 2 times at the discretion of the investigator - Echocardiogram or multiple-gated acquisition (MUGA) scan with LVEF > 50% - Subjects with a history of COVID-19 infection must be discussed with the medical monitor prior to enrollment. Subjects with a history of COVID-19 infection must have a negative qPCR test prior to enrollment. - Subjects with a history of coronary artery disease, heart failure, cardiac arrythmia, or prior COVID-19 infection must have a cardiology consultation during screening, to include advice on appropriate management of subjects during episodes of CRS. - Serum sodium, potassium, calcium, and magnesium must be normal. If abnormal, must be have resolved to CTCAE Grade <= 1 within 7 days of day 1. Subjects not meeting these inclusion criteria may be treated with replacement therapy and re-screened up to 2 times at the discretion of the investigator. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adult
Exclusion criteria
Exclusion criteria: •Known extramedullary relapse in the absence of any measurable medullary involvement (exception: this exclusion criteria only applies to phase 1a (dose escalation) study. •Known central nervous system involvement by multiple myeloma •Previously received an allogeneic stem cell transplant and the occurrence of 1 or more of the following: - received the transplant within 6 months prior to study day 1 - received immunosuppressive therapy within the last 3 months prior to study day 1 - any active acute graft versus host disease (GvHD) requiring systemic therapy within the last 4 weeks prior to start of study treatment - any systemic therapy against GvHD within 4 weeks prior to start of investigational product treatment •Autologous stem cell transplantation less than 90 days prior to study day 1 •Recent history of primary plasma cell leukemia (within last 6 months prior to enrollment) or evidence of primary or secondary plasma cell leukemia at the time of screening •Waldenstrom's macroglobulinemia •Prior amyloidosis (patients with multiple myeloma with asymptomatic deposition of amyloid plaques found on biopsy would be eligible if all other criteria are met) •Treatment with systemic immune modulators including, but not limited to, non-topical systemic corticosteroids •Last anticancer treatment (chemotherapy, IMiD, PI, molecular targeted therapy) 470
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Phase 1 – dose-exploration as monotherapy -Evaluate the safety and tolerability of AMG 701 in subjects with relapsed/refractory multiple myeloma (RRMM) to determine the maximum tolerated dose (MTD) and/or recommended phase 2 dose [RP2D]). Phase 1b – AMG 701 dose-confirmation as monotherapy -Establish the safety and tolerability of AMG 701 at the RP2D Phase 1/1b -– AMG 701 in combination with Pomalidomide, with and without Dexamethasone (AMG 701-P ± d) -Evaluate the safety and tolerability of AMG 701 and determine the AMG 701 RP3D in combination with pomalidomide (P), with and without dexamethasone (± d) in subjects with RRMM Phase 2 - AMG 701 monotherapy dose - expansion -Estimate ORR per IMWG response criteria (sCR, CR, VGPR, PR);Secondary Objective: Phase 1 –dose-exploration as monotherapy -Characterize the pharmacokinetics (PK) of AMG 701 when administered by intravenous infusion -Estimate anti-myeloma activity of AMG 701 -Estimate duration of response (DOR) of AMG 701 -Estimate other measures of anti myeloma activity of AMG 701 Phase 1b –AMG701 dose-confirmation as monotherapy - Estimate anti-myeloma activity of AMG 701: - Evaluate the rate of minimum residual disease negative CR (MRD[-]CR) - Characterize the PK of AMG 701 by IV infusion - Evaluate other measures of anti-myeloma activity of AMG 701 Phase 1/1b -– AMG701 in combination with Pomalidomide, with and without Dexamethasone (AMG 701-P ± d) - Characterize the PK of AMG701 when administered by intravenous (IV) infusion -Estimate anti-myeloma activity of: •AMG 701-P±d in each treatment group •AMG 701-P±d in each treatment group at the RP3D - Estimate the rate of MRD[-]CR For all secondary objectives please check protocol;Primary end point(s): Phase 1 – dose-exploration as monotherapy: -Dose limiting toxicities (DLTs), treatment-emergent adverse events, treatment-related adverse events -Clinically-significant changes in vital signs, physical examinations, electrocardiogram (ECG)s, and | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Phase 1 – AMG 701 dose exploration as monotherapy: - AMG 701 PK parameters including, but not limited to, maximum concentration (Cmax), time of maximum concentration (Tmax) area under the concentration-time curve (AUC), and steady state concentration (Css) for extended IV o Efficacy parameters: - overall response (OR) according to International Myeloma Working Group (IMWG) response criteria (BOR of stringent CR [sCR],complete response [CR],very good partial response [VGPR], or Partial [PR]) - BOR by category (sCR, CR, VGPR, PR), MR, stable disease [SD], progressive disease [PD] -DOR (defined as time from the first PR or better to disease progression or death) -Time to response - Progression free survival (PFS), defined as time from start of treatment until disease progression or death - Overall survival (OS), defined as time from start of treatment until death due to any cause. Phase 1b – AMG 701 dose confirmation as monotherapy: o Efficacy parameters: - OR according to IMWG response criteria (best overall response of stringent CR, CR, VGPR, or PR) - Duration of response (DOR) - BOR by category (sCR, CR, VGPR, PR, MR, SD, PD) o MRD[-]negativity at the time of CR rate at level of <10^5 - AMG 701 PK parameters including, but not limited to, Cmax, Tmax, AUC, and Css for extended IV - Efficacy parameters according to IMWG response criteria: - time to response - progression-free survival (PFS) - overall survival (OS) Phase 1/1b -– AMG701 in combination with Pomalidomide, with and without Dexamethasone (AMG 701-P ± d): o AMG 701 PK parameters including, but not limited to: Cmax, Tmax, AUC, and Css for extended IV o ORR per IMWG response criteria (sCR, CR, VGPR, PR) -BOR by category (sCR, CR, VGPR, PR, MR, SD, PD) -DOR -Time to response -PFS -OS o MRD[-]CR rate at level of 10-5 o Pomalidomide PK parameters including, but not limited to: Cmax and trough concentration (Ctrough) Phase 2 – AMG 701 monotherapy dose-expansion: o DOR o MRD[-]n | — |
Countries
Australia, Belgium, Canada, France, Germany, Japan, Netherlands, Spain, United States
Contacts
Public ContactMedical Information The Netherlands
Amgen Nederland
Outcome results
None listed