A Phase 1/2 Study to Assess AMG 701 Monotherapy, or in Combination with Pomalidomide with or without Dexamethasone in Subjects with Relapsed or Refractory Multiple Myeloma

Phase 1

• Conditions: Subjects with pathologically documented relapsed/ refractory multiple myeloma; MedDRA version: 21.0Level: LLTClassification code 10028228Term: Multiple myelomaSystem Organ Class: 100000004864; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2017-001997-41-DE
• Lead Sponsor: Amgen Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2017-09-22
• Last Update Posted: 3 May 2021

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 408

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) < 3 x upper limit of normal (ULN)
- total bilirubin < 1.5 x the ULN, unless subject has Gilbert’s syndrome (see below)
- In patients with Gilberts syndrome, enrollment will be allowed if the level of total bilirubin (TBIL) falls within the CTCAE grade 2 (ie, < 3 x ULN, which is < 3.6 mg/dL if the upper limit of normal is 1.2 mg)
Serum phosphate as follows:
- Serum phosphorus >= 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

•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) < 2 weeks prior to study day 1
•Last treatment with a therapeutic antibody less than 4 weeks prior to study day 1
•Radiation therapy to multiple anatomic sites within 28 days prior to study day 1. Focal radiotherapy within 14 days prior to study day 1.
•Major surgery defined as surgery requiring general anesthesia with endotracheal intubation within 28 days prior to study day 1, unless discussed with and eligibility approved by Amgen medical monitor
•Prior treatment with any drug or construct that targets BCMA on tumor cells (eg, other bispecific antibody constructs, antibody drug conjugates, or CAR-T cells), other than group 2 where prior treatment with BCMA targeting agent is required.
•Currently receiving treatment in another investigational device or drug study, or less than 30 days since ending treatment on another investigational device or drug study. Other investigational procedures while participating in this study are excluded.
•Treatment with medications known to cause QTc interval prolongation within the washout periods described in Section 12.9 of the protocol unless approved by the Amgen medical monitor
•Unresolved toxicities from prior anticancer therapy, defined as not having resolved to CTCAE version 4.0 grade 1 or to levels dictated in the eligibility criteria with the exception of grade 2 peripheral neuropathy, alopecia or toxicities from prior anticancer therapy that are considered irreversible
•Clinically-not controlled chronic or ongoing bacterial, fungal, viral or other infectious disease requiring treatment at the time of study day 1 or within the 14 days before study day 1
•Active hepatitis B and C based on the following results:
- Positive for hepatitis B surface antigen (HepBsAg) (indicative of chronic hepatitis B or recent acute hepatitis B)
- Negative HepBsAg and positive for hepatitis B core antibody: Negative hepatitis B virus DNA by polymerase chain reaction (PCR) result is necessary.
- Positive Hepatitis C virus antibody (HepCAb): Negative hepatitis C virus RNA by PCR result is necessary.
•Positive results for human immunodeficiency virus (HIV)
•Baseline ECG QTc > 470

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified