NCT03836053 · REGISTRY CONDITION SEARCH

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

Found through the registry condition index, not selected as a treatment recommendation. This discovery collection was restricted to studies with posted results.

Phase: PHASE1
Status at capture: TERMINATED
Registry last update: 2025-09-11

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.

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

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baseline

Baseline characteristics

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outcome · POSTED

Number of Participants With Dose-limiting Toxicities (DLTs)

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outcome · POSTED

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

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outcome · POSTED

Overall Response Rate (ORR)

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outcome · POSTED

Duration of Response (DOR)

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outcome · POSTED

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

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outcome · POSTED

Number of Participants Who Experienced a Treatment-related TEAE

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outcome · POSTED

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

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adverse events

Adverse events

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more info

Limitations, agreements, and source contact

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Who could take part

eligibility Criteria: Key Inclusion Criteria: 1. Subject has provided informed consent prior to initiation of any study specific activities/procedures 2. Multiple myeloma meeting the following criteria: 3. 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 4. . ECOG performance status of less than or equal to 2 5. Life expectancy of at least 3 months per PI judgement at screening 6. 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) 7. 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 8. 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) Key Exclusion Criteria: 1. Known central nervous system involvement by multiple myeloma 2. Evidence of primary or secondary plasma cell leukemia at the time of screening 3. Waldenstrom's macroglobulinemia 4. Unresolved toxicities from prior anticancer therapy, defined as not having resolved to CTCAE version 5.0 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 (defined as having been present and stable for \> 4 weeks) which may be allowed if they are not otherwise described in the exclusion criteria and there is agreement to allow by the PI and Amgen medical monitor 5. History of other malignancy within the past 3 years, with the following exceptions: 1. malignancy treated with curative intent and with no known active disease present for ≥ 1 year before enrollment and felt to be at low risk for recurrence by the treating physician; 2. adequately-treated non-melanoma skin cancer or lentigo maligna without evidence of disease; 3. adequately-treated cervical carcinoma in situ without evidence of disease; 4. breast ductal carcinoma in situ with full surgical resection (ie, negative margins) and without evidence of disease; 5. prostate cancer with a Gleason score \< 6 with undetectable PSA over 12 months; 6. treated medullary or papillary thyroid cancer; 7. adequately-treated urothelial papillary noninvasive carcinoma or carcinoma in situ; similar neoplastic conditions with an expectation of \> 95% five-year disease-free survival; 8. see exclusion criterion # 2 for exclusion of subjects with evidence of primary or secondary plasma cell leukemia at the time of screening 6. Known history of amyloidosis 7. 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. 8. 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 9. Symptomatic peripheral sensory or motor neuropathy of grade ≥3 10. 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 11. 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) 12. Known or suspected HIV infection or subjects who are HIV seropositive 13. Baseline ECG QTc \> 470 msec (applying Fridericia correction) 14. 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 15. Autologous stem cell transplantation \< 90 days prior to study day 1 16. 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 17. Last anticancer treatment \< 2 weeks prior to study day 1 18. Last treatment with a therapeutic antibody less than 4 weeks prior to study day 1 19. Systemic radiation therapy within 28 days prior to study day 1. Focal radiotherapy within 14 days prior to study day 1. 20. 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 21. Prior treatment with any drug that specifically targets BCMA on tumor cells (eg, other bi-specific antibody constructs, antibody drug conjugates, or CAR T-cells, except for subjects who were previously treated with AMG 420 in this study and who are candidates for second-course treatment 22. Treatment with medications known to cause QTc interval prolongation within the washout periods described in Section 12.10 unless approved by the Amgen medical monitor 23. 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(ies). Other investigational procedures while participating in this study are excluded. 24. History or evidence of any other clinically-significant disorder, condition, or disease (eg, symptomatic congestive heart failure, unstable angina pectoris,cardiac arrhythmia requiring therapy at time of screening) with the exception of those outlined above that, in the opinion of the investigator or Amgen medical monitor, if consulted, would pose a risk to subject safety or interfere with the study evaluation, procedures, or completion.
healthy Volunteers: false
minimum Age: 18 Years
sex: ALL
std Ages: ADULT
OLDER_ADULT

Treatment arms and interventions

arm Groups

description
Single Arm Design
intervention Names
Drug: AMG 420
label
AMG 420
type
EXPERIMENTAL

interventions

arm Group Labels
AMG 420
description
28 day continuous Intravenous infusion of either 400 mcg/d or 600 mcg/d followed by 2 treatment free weeks
name
AMG 420
type
DRUG

Study design

allocation

intervention Model

SINGLE_GROUP

intervention Model Description

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

masking Info

masking: NONE

primary Purpose

TREATMENT

Enrollment

count: 23
type: ACTUAL

Registered outcome plans (not posted results)

primary Outcomes

description
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.
measure
Number of Participants With Dose-limiting Toxicities (DLTs)
time Frame
Day 1 to Week 4
description
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.
measure
Number of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)
time Frame
Up to approximately 3 years
description
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.
measure
Number of Participants Who Experienced a Treatment-related TEAE
time Frame
Up to approximately 3 years

secondary Outcomes

description
ORR was defined as the percentage of participants for whom the best overall response was a stringent complete response (CR), CR, very good partial response (PR), or partial response as determined by the IMWG Uniform Response Criteria. The ORR along with the associated 95% exact binomial confidence interval (Clopper Pearson Method) was determined.
measure
Overall Response Rate (ORR)
time Frame
Up to approximately 3 years
description
DOR was defined as number of months between first objective response to progressive disease or death (due to any cause), whichever occurred first. Kaplan-Meier methods were used to estimate the distribution of DOR. The median and corresponding two-sided 95% confidence intervals were calculated.
measure
Duration of Response (DOR)
time Frame
Up to approximately 3 years
description
MRD negativity at CR or better assessed by using the IMWG criteria. Percentage of MRD negative responders at CR along with exact 2- sided 95% were provided by using the Clopper Pearson method.
measure
Percentage of Participants With Minimal Residual Disease (MRD) Negativity Response at CR
time Frame
Up to approximately 3 years
description
Number of participants with MRD negativity at CR or better assessed by using the IMWG criteria.
measure
Number of Participants With Minimal Residual Disease (MRD) Negativity Response at CR
time Frame
Up to approximately 3 years

Full study description

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.
detailed Description: Cohort 1 will consist of 10 subjects dosed at 400 mcg/d. Cohort 2 will consist of 10 subjects dosed at 600 mcg/d. All doses will be given as a 28-day continuous IV infusion, followed by a 2 week treatment-free interval, until subject experiences disease progression as per International Myeloma Working Group (IMWG) criteria.

Source references

references

citation
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
type
BACKGROUND