A Phase 1/2 Open-label Study Evaluating the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Efficacy of AMG 701 Monotherapy, or in Combination with Pomalidomide, with and without Dexamethasone in Subjects with Relapsed or Refractory Multiple Myeloma (ParadigMM-1B)

Completed

• Conditions: plasma cel myeloom; Ziekte van Kahler; 10018865

• Registration Number: NL-OMON52671
• Lead Sponsor: Amgen

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Last Update Posted: 15 April 2024

Recruitment & Eligibility

• Status: Completed
• Sex: Not specified
• Target Recruitment: 20

Inclusion Criteria

• Age >= 18 years at the time of signing the informed consent
• Multiple Myeloma meeting the following criteria:
- Pathologically-documented diagnosis of multiple myeloma that has is relapsed
after or is refractory (see section
12.14) as defined by the following:
o 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 where approved and available, a CD38-directed cytolytic
antibody in combination in the same line or separate
lines of treatment OR refractory to PI, IMiD and CD38-directed
cytolytic antibody.
o 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 one or more of the following at time of
screening:
o a serum M protein > 0.5 g/dl measured by serum protein electrophoresis
o urinary M protein excretion > 200 mg/24 hours
o involved serum free light chain (sFLC) measurement > 10 mg/dl, provided that
the sFLC ratio is abnormal (< 0.26 or
> 1.65) as per IMWG response criteria
• ECOG Performance Status of <= 2
• 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); platelet count between
25 and 50 x 109/L at time of enrollment requires agreement by both the
Investigator and Amgen Medical Monitor of
acceptability before enrollment can be approved
- hemoglobin > 8 g/dL
• 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)

Refer to section 6.1 of the protocol.

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
one 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 IP
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
othercriteria are met)
• Treatment with systemic immune modulators including, but not limited to,
nontopical systemic corticosteroids (unless the dose is <= 10 mg/day
prednisolone or equivalent), cyclosporine, and tacrolismus within 2 weeks
before study day 1
• Last anticancer treatment (*) < 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.
• 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
• Baseline ECG QTc > 470 msec (applying Fridericia correction), defined as the
average of individual baseline ECGs
• History of malignancy other than multiple myeloma within the past 3 years
with exceptions listed in the protocol
section 6.2.
• Current or known history of autoimmune diseases requiring systemic treatment
in past 5 years, excluding
autoimmune thyroid disease, for which treatment should be completed 6
months prior to enrollment.

Refer to section 6.2 of the protocol.

Study & Design

• Study Type: Interventional
• Study Design: Not specified