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

Key Inclusion Criteria:

1. Subject has provided informed consent prior to initiation of any study specificactivities/procedures

2. Multiple myeloma meeting the following criteria:

3. Pathologically-documented diagnosis of multiple myeloma that is relapsed or isrefractory as defined by the following: Relapsed after 3 or more lines of priortherapy that must include a proteasome inhibitors (PI), an immunomodulators (IMiD),and a CD38-directed monoclonal antibody in any order during the course of treatmentOR 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 screeningassessment) 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 beforescreening)

7. Renal function as follows: calculated or measured creatinine clearance ≥30 mL/minusing the Cockcroft-Gault equation or via 24-hour urine collection with plasma andurine creatinine concentrations, respectively

8. Hepatic function as follows: AST and ALT < 3x upper limit of normal (ULN); TBIL <1.5x 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 resolvedto CTCAE version 5.0 grade 1 or to levels dictated in the eligibility criteria withthe exception of grade 2 peripheral neuropathy, alopecia, or toxicities from prioranticancer therapy that are considered irreversible (defined as having been presentand stable for > 4 weeks) which may be allowed if they are not otherwise describedin the exclusion criteria and there is agreement to allow by the PI and Amgenmedical monitor

5. History of other malignancy within the past 3 years, with the following exceptions:

6. malignancy treated with curative intent and with no known active disease presentfor ≥ 1 year before enrollment and felt to be at low risk for recurrence by thetreating physician; 2. adequately-treated non-melanoma skin cancer or lentigomaligna without evidence of disease; 3. adequately-treated cervical carcinoma insitu without evidence of disease; 4. breast ductal carcinoma in situ with fullsurgical 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 urothelialpapillary noninvasive carcinoma or carcinoma in situ; similar neoplastic conditionswith an expectation of > 95% five-year disease-free survival; 8. see exclusioncriterion # 2 for exclusion of subjects with evidence of primary or secondary plasmacell leukemia at the time of screening

7. Known history of amyloidosis

8. Current or known history of autoimmune diseases requiring systemic treatment in past 5 years except vitiligo, resolved childhood asthma/atopy, or subjects with historyof hypothyroidism after completing treatment for autoimmune thyroid disease, stableon hormone replacement therapy.

9. Clinically not-controlled chronic or ongoing infectious disease requiring treatmentat the time of study day 1 or within the 14 days before study day 1

10. Symptomatic peripheral sensory or motor neuropathy of grade ≥3

11. History or presence of clinically relevant central nervous system (CNS) pathology asuncontrolled epilepsy or seizure disorder, paresis, aphasia, stroke, severe braininjuries, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome,and psychosis

12. 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 Cvirus antibody (HepCAb)

13. Known or suspected HIV infection or subjects who are HIV seropositive

14. Baseline ECG QTc > 470 msec (applying Fridericia correction)

15. Previously received an allogeneic stem cell transplant and the occurrence of 1 ormore 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 tothe Glucksberg criteria or active chronic GvHD requiring systemic treatment; d) anysystemic therapy against GvHD within 2 weeks prior to start of investigationalproduct treatment

16. Autologous stem cell transplantation < 90 days prior to study day 1

17. Treatment with systemic immune modulators including, but not limited to, nontopicalsystemic corticosteroids (unless the dose is ≤ 10 mg/day prednisone or equivalent),cyclosporine, and tacrolimus within 2 weeks before study day 1

18. Last anticancer treatment < 2 weeks prior to study day 1

19. Last treatment with a therapeutic antibody less than 4 weeks prior to study day 1

20. Systemic radiation therapy within 28 days prior to study day 1. Focal radiotherapywithin 14 days prior to study day 1.

21. Major surgery defined as surgery requiring general anesthesia with endotrachealintubation within 28 days prior to study day 1, unless discussed with andeligibility approved by Amgen medical monitor

22. 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 whoare candidates for second-course treatment

23. Treatment with medications known to cause QTc interval prolongation within thewashout periods described in Section 12.10 unless approved by the Amgen medicalmonitor

24. Currently receiving treatment in another investigational device or drug study, orless than 30 days since ending treatment on another investigational device or drugstudy(ies). Other investigational procedures while participating in this study areexcluded.

25. History or evidence of any other clinically-significant disorder, condition, ordisease (eg, symptomatic congestive heart failure, unstable angina pectoris,cardiacarrhythmia requiring therapy at time of screening) with the exception of thoseoutlined above that, in the opinion of the investigator or Amgen medical monitor, ifconsulted, would pose a risk to subject safety or interfere with the studyevaluation, procedures, or completion.