Assessment of AMG 420 in Subjects With Relapsed and/or Refractory Multiple Myeloma

NCT03836053 | Terminated Phase 1 Results FDA Drug

• 2 other identifiers: 201603702018-002879-17
• Study Type: interventional
• Target: 23
• Locations: 5 countries
• Sites: 10

Brief Summary

To confirm the maximum tolerated dose (MTD) from the BI 836909 trial of 400 mcg/d, given as 28-day continuous intravenous infusion in patients with relapsed and/or refractory multiple myeloma, to test the 600 mcg/d dose, given as a 28-day continuous iV infusion.

Conditions

Relapsed and/or Refractory Multiple Myeloma

Outcome Measures

Primary Outcomes (3)

• Number of Participants With Dose-limiting Toxicities (DLTs)

  DLTs were graded using Common Terminology Criteria for Adverse Events (CTCAE) v5.0, with the exception of cytokine release syndrome (CRS) and tumor lysis syndrome (TLS), which graded using the criteria referenced in the publication by Lee et al, 2014 and the Cairo Bishop criteria referenced in the publication by Coiffier et al, 2008 respectively. A participant was non-DLT evaluable if they dropped out before completion of the DLT-evaluable period for reasons other than a DLT.

  Day 1 to Week 4

• Number of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)

  The severity of TEAEs were graded using the CTCAE version 5.0 with the exception of CRS and TLS, which graded using the criteria referenced in the publication by Lee et al, 2014 and the Cairo Bishop criteria referenced in the publication by Coiffier et al, 2008. Any clinically significant changes in vital signs, electrocardiograms (ECGs) and clinical laboratory tests were recorded as TEAEs.

  Up to approximately 3 years

• Number of Participants Who Experienced a Treatment-related TEAE

  The severity of treatment-related TEAEs were graded using the CTCAE version 5.0 with the exception of CRS and TLS, which graded using the criteria referenced in the publication by Lee et al, 2014 and the Cairo Bishop criteria referenced in the publication by Coiffier et al, 2008. Treatment-related TEAEs were those that were considered related to the study treatment by the investigator.

  Up to approximately 3 years

Secondary Outcomes (4)

• Overall Response Rate (ORR)

  Up to approximately 3 years

• Duration of Response (DOR)

  Up to approximately 3 years

• Percentage of Participants With Minimal Residual Disease (MRD) Negativity Response at CR

  Up to approximately 3 years

• Number of Participants With Minimal Residual Disease (MRD) Negativity Response at CR

  Up to approximately 3 years

Study Arms (1)

AMG 420

EXPERIMENTAL

Single Arm Design

Drug: AMG 420

Interventions

AMG 420 DRUG

28 day continuous Intravenous infusion of either 400 mcg/d or 600 mcg/d followed by 2 treatment free weeks

AMG 420

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subject has provided informed consent prior to initiation of any study specific activities/procedures
• 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 or more lines of prior therapy that must include a proteasome inhibitors (PI), an immunomodulators (IMiD), and a CD38-directed monoclonal antibody in any order during the course of treatment OR refractory to a PI, IMiD, and CD38-directed monoclonal antibody.
• Measurable disease, defined by 1 or more of the following at time of screening: 1) serum M-protein \> 0.5 g/dL measured by serum protein electrophoresis (SPEP); 2) urinary M-protein excretion \> 200 mg/24 hours; 3) 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 less than or equal to 2
• Life expectancy of at least 3 months per PI judgement at screening
• Hematological function without transfusion support (within 7 days from screening assessment) as follows:
• ANC ≥ 1.0 x 10\^9/L (without growth factor support)
• platelet count ≥ 25 x 10\^9/L (without transfusions)
• hemoglobin ≥ 7.0 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, respectively
• Hepatic function as follows: AST and ALT \< 3x upper limit of normal (ULN); TBIL \<1.5 x ULN (unless considered due to Gilbert's syndrome)

You may not qualify if:

• Known central nervous system involvement by multiple myeloma
• Evidence of primary or secondary plasma cell leukemia at the time of screening
• Waldenstrom's macroglobulinemia
• Known history of amyloidosis
• Current or known history of autoimmune diseases requiring systemic treatment in past 5 years except vitiligo, resolved childhood asthma/atopy, or subjects with history of hypothyroidism after completing treatment for autoimmune thyroid disease, stable on hormone replacement therapy.
• Clinically not-controlled chronic or ongoing infectious disease requiring treatment at the time of study day 1 or within the 14 days before study day 1
• Symptomatic peripheral sensory or motor neuropathy of grade ≥3
• History or presence of clinically relevant central nervous system (CNS) pathology as uncontrolled epilepsy or seizure disorder, paresis, aphasia, stroke, severe brain injuries, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome, and psychosis
• Active hepatitis B and C based on the following results: a) Positive for HepBsAg; b) Negative HepBsAg and positive for hepatitis B core antibody; c) Positive Hepatitis C virus antibody (HepCAb)
• Known or suspected HIV infection or subjects who are HIV seropositive
• Baseline ECG QTc \> 470 msec (applying Fridericia correction)
• Previously received an allogeneic stem cell transplant and the occurrence of 1 or more of the following: a) received the transplant within 6 months prior to study day 1; b) received immunosuppressive therapy within the last 3 months prior to study day 1; c) any active acute graft versus host disease (GvHD), grade 2 to 4, according to the Glucksberg criteria or active chronic GvHD requiring systemic treatment; d) any systemic therapy against GvHD within 2 weeks prior to start of investigational product treatment
• Autologous stem cell transplantation \< 90 days prior to study day 1
• Treatment with systemic immune modulators including, but not limited to, nontopical systemic corticosteroids (unless the dose is ≤ 10 mg/day prednisone or equivalent), cyclosporine, and tacrolimus within 2 weeks before study day 1
• Last anticancer treatment \< 2 weeks prior to study day 1

Sponsors & Collaborators

• Amgen: lead

Study Sites (10)

Advocate Lutheran General Hospital

Park Ridge, Illinois, 60068, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10021, United States

Location

Wake Forest Baptist Health

Winston-Salem, North Carolina, 27157, United States

Location

St Vincents Hospital Sydney

Darlinghurst, New South Wales, 2010, Australia

Location

St Vincents Hospital Melbourne

Fitzroy, VIC, Victoria, 3065, Australia

Location

Centres Hospitaliers Jolimont - Hopital de Jolimont

Haine Saint Paul - La Louviere, 7100, Belgium

Location

Centre Hospitalier Universitaire Dinant Godinne - Universite Catholique de Louvain Namur

Yvoir, 5530, Belgium

Location

National Hospital Organization Okayama Medical Center

Okayama, Okayama-ken, 701-1192, Japan

Location

Kantonsspital St Gallen

Sankt Gallen, 9007, Switzerland

Location

Related Publications (1)

• Rodriguez C, Rodriguez T, Kentos A, Driessen C, Sunami K, Lesokhin AM, Yee AJ, Minella AC, Maraboina R, Upreti VV, Zhou D, Shabooti M, Stieglmaier J, Quach H. BCMA-targeting BiTE molecule AMG 420 in relapsed or refractory multiple myeloma: a phase 1b open-label expansion study. Leuk Lymphoma. 2025 Nov;66(11):2108-2117. doi: 10.1080/10428194.2025.2528115. Epub 2025 Jul 21.

  PMID: 40690374 BACKGROUND

Related Links

• AmgenTrials clinical trials website

Limitations and Caveats

The study was terminated early due to sponsor decision and long-term follow-up was cancelled.

Results Point of Contact

• Title: Study Director
• Organization: Amgen Inc.

medinfo@amgen.com

866-572-6436

Study Officials

• MD

  Amgen

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Phase 1b Primary objective Establish the safety and tolerability of AMG 420 at dose levels of 400 mcg/day and 600 mcg/day in subjects with relapsed and/or refractory multiple myeloma (RRMM) Phase 1b Key Secondary/Secondary objectives: Estimate overall response rate (ORR) and duration of response (DOR) Evaluate the rate of minimal residual disease (MRD)-negativity at the time of CR Establish the safety and tolerability of AMG 420 in subjects with extramedullary relapsed MM Characterize the PK of AMG 420 when administered as 4-week continuous IV infusion Evaluate other measures of anti-myeloma activity of AMG 420: Time to response, PFS, OS, TFI, BOR

Study Record Dates

• First Submitted: February 5, 2019
• First Posted: February 11, 2019
• Study Start: March 4, 2019
• Primary Completion: April 21, 2022
• Study Completion: April 21, 2022
• Last Updated: September 11, 2025
• Results First Posted: January 5, 2024

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: Data sharing requests relating to this study will be considered beginning 18 months after the study has ended and either 1) the product and indication (or other new use) have been granted marketing authorization in both the US and Europe or 2) clinical development for the product and/or indication discontinues and the data will not be submitted to regulatory authorities. There is no end date for eligibility to submit a data sharing request for this study.
• Access Criteria: Qualified researchers may submit a request containing the research objectives, the Amgen product(s) and Amgen study/studies in scope, endpoints/outcomes of interest, statistical analysis plan, data requirements, publication plan, and qualifications of the researcher(s). In general, Amgen does not grant external requests for individual patient data for the purpose of re-evaluating safety and efficacy issues already addressed in the product labelling. Requests are reviewed by a committee of internal advisors, and if not approved, may be further arbitrated by a Data Sharing Independent Review Panel. Upon approval, information necessary to address the research question will be provided under the terms of a data sharing agreement. This may include anonymized individual patient data and/or available supporting documents, containing fragments of analysis code where provided in analysis specifications. Further details are available at the link below.

Locations

US (4); AU (2); BE (2); CH (1); JP (1)