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

Overview

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, and to expand on the dose determined as the Recommended Phase 2 Dose (RP2D).

Cohort 1 will consist of 10 subjects dosed at 400 mcg/d. Cohort 2 will consist of 10 subjects dosed at 600 mcg/d. Cohort 3 (Phase 2) will consist of 100 subjects dosed at 400 mcg/d. If the 600 mcg/d dose is determined to be superior, Phase 2 subjects may potentially receive this dose. 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.

SparkCures ID 990
Trial Phase Phase 1
Enrollment 120 Patients
Treatments
Trial Sponsors
  • Amgen
NCT Identifier

NCT03836053

Am I Eligible?

The following criteria is a partial list of reasons why patients may or may not be eligible to participate in this clinical trial. Further evaluation with a medical professional will be required to determine full eligibility.

The following criteria is provided for health care professionals.

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:
    • 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 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
  3. ECOG performance status of less than or equal to 2
  4. Life expectancy of at least 3 months per PI judgement at screening
  5. 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)
  6. 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
  7. 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.

US Trial Locations

Accepting Patients

The following is a listing of trial locations that are open and accepting patients.

Not Currently Accepting Patients

The following is a listing of trial locations that are not currently open and accepting patients.

Massachusetts
New York
North Carolina

Resources

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