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

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.

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.