A Phase IV Study to Learn About the Study Medicine Called Elranatamab in People With Multiple Myeloma That is Not Responding to Four or More Standard Treatments or Has Come Back After Several Standard Treatments

Inclusion Criteria

Participants are eligible to be included in this study only if all of the following criteria apply:

Age and Sex:

1. 18 years of age or older (or the minimum age of consent in accordance with local regulations) at screening.

• Refer to Appendix 4 for reproductive criteria for male (Section 10.4.1) and female (Section 10.4.2) participants.

Disease Characteristics:

2. Prior diagnosis of MM as defined according to IMWG criteria and currently having at least 1 of the following
   • Serum M-protein ≥0.5 g/dL by SPEP
   • Urinary M-protein excretion ≥200 mg/24 hours by UPEP
   • Serum immunoglobulin FLC ≥10 mg/dL (≥100 mg/L) AND abnormal serum immunoglobulin kappa to lambda FLC ratio (<0.26 or >1.65).
3. Previously received at least four prior therapies, including an immunomodulatory agent, a proteasome inhibitor and an anti-CD38 antibody.

Other Inclusion criteria:

4. Must sign an informed consent form indicating that the participant understands the purpose and procedures required for the study treatment plan; required concomitant medications, laboratory test and are willing to participate.
5. ECOG PS 0 or 1 5.2. Exclusion Criteria

Participants are excluded from the study if any of the following criteria apply:

Medical Conditions:

1. Any of the conditions mentioned below:
   • Plasma cell leukemia (anytime prior study entry) , Smoldering MM (at study entry), Waldenström's macroglobulinemia (anytime prior study entry), Amyloidosis (anytime prior study entry).
   • POEMS Syndrome.
   • Known CNS involvement or clinical signs of myelomatous meningeal involvement.
   • History of stem cell transplant within 12 weeks prior to enrollment.
   • Active GVHD (other than Grade 1 skin involvement), or GVHD requiring treatment.
   • Participants with any other active malignancy within 3 years prior to enrollment, except for adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ of the cervix, Bowen's disease.
   • Ongoing Grade 2 or higher peripheral sensory or motor neuropathy.
   • History of GBS or GBS variants, or history of any Grade ≥3 peripheral motor polyneuropathy.
2. Known or suspected hypersensitivity to elranatamab or any other study interventions or any of their excipients.
3. Any medical or psychiatric condition including any active suicidal ideation in the past year or suicidal behavior in the past 5 years or laboratory abnormality that may increase the risk of study participation or, in the investigator's judgment, make the participant inappropriate for the study.

Prior/Concomitant Therapy:

4. Previous treatment with an anti-BCMA bispecific antibody or a CD3-redirecting therapy.
5. Cumulative dose of corticosteroids equivalent to ≥140 mg of prednisone within the 14-day period before the first dose of study intervention.
6. Any anti-myeloma drug therapy within 14 days of the first dose of study intervention (includes dexamethasone). Bisphosphonate use permitted.
7. Live attenuated vaccine must not be administered within 4 weeks of the first dose of study intervention.

Prior/Concurrent Clinical Study Experience:

8. Previous administration with an investigational product (drug or vaccine) within 30 days (or as determined by the local requirement) or 5 half-lives preceding the first dose of study intervention used in this study (whichever is longer). A participant may be eligible even if they are in the follow-up phase of an investigational study if they meet the criterion for time elapsed from previous administration of investigational product. Cases must be discussed with sponsor's medical monitor to judge eligibility.

Diagnostic Assessments:

9. Hepatic dysfunction defined as having any 1 of the following, which may be confirmed by a single repeat test, if necessary:
   • Total bilirubin >2 × ULN (except for Gilbert's syndrome, direct bilirubin >3 × ULN is exclusionary)
   • AST >2.5 × ULN
   • ALT >2.5 × ULN
10. Hematologic abnormalities defined as any 1 of the following,:
    • ANC <1000/mm3,(use of G-CSFs is permitted if completed at least 7 days prior to eligibility sample collection and at least 7 days prior to planned start of dosing)
    • Platelet count <75,000/μL if <50% of BM nucleated cells are plasma cells, or <50,000/μL if ≥50% of BM nucleated cells are plasma cells (transfusion support is permitted if completed at least 7 days prior to eligibility sample collection and at least 7 days prior to planned start of dosing); and
    • Hemoglobin <8 g/dL (transfusion support is permitted if completed at least 14 days prior to eligibility sample collection and at least 14 days prior to planned start of dosing).
    • NOTE: Hematologic parameters are also to be met on C1D1 prior to proceeding with study treatment.
11. Active HBV, HCV, SARS-CoV-2, known HIV or AIDS, or any active, uncontrolled bacterial, fungal, or viral infection. Active infections must be resolved at least 21 days prior to enrollment. Treatment with systemic anti-infective agents must be completed at least 28 days prior to enrollment. Prophylactic use of systemic anti-infective agents is permitted. Participants whose HIV or HCV status cannot be determined from their medical history must be screened for HIV and HCV up to 28 days prior to enrollment.

1. COVID-19/SARS-CoV-2: SARS-CoV-2 PCR testing is mandated within 5 days prior to enrollment. Participants with positive PCR test result for SARS-CoV-2 within 5 days prior to enrollment, or suspected of having SARS-CoV-2, are excluded.
2. HIV: In equivocal cases, participants whose viral load is negative may be eligible. HIV seropositive participants who are otherwise healthy and at low risk for AIDS-related outcomes could be considered eligible. Potential eligibility for a specific HIV positive protocol candidate should be evaluated and discussed with the sponsor prior to screening, considering current and past CD4+ and T-cell counts, history (if any) of AIDS defining conditions (eg, opportunistic infections), status of HIV treatment and the potential for drug-drug interactions.
3. HBV:
   • Participants with a positive HBsAg test (ie, either acute or chronic active hepatitis) are excluded.
   • Participants with HBV antibody positivity indicating immunity, either due to vaccination or prior natural infection, are eligible.
   • Participants with positive anti-HBcAb but negative HBsAg and negative anti-HBsAb profile are eligible if HBV DNA is not detected. See Appendix 15.
   • For additional details, refer to CDC website (https://www.cdc.gov/hepatitis/HBV/PDFs/SerologicChartv8.pdf).
4. HCV: Positive HCV antibody is indicative of infection but may not necessarily render a potential candidate ineligible, depending on clinical circumstances. If exposure to HCV is recent, HCV antibody may not have yet turned positive. In these circumstances it is recommended to test for HCV RNA. If HCV RNA is detected, the patient is not eligible. Refer to CDC website for further details (https://www.cdc.gov/hepatitis/hcv/pdfs/hcv\_graph.pdf).
5. Lung imaging is required within 7 days prior to enrollment. Participants with evidence of active respiratory infection are excluded

12. Any of the following in the previous 6 months: myocardial infarction, long QT syndrome, Torsade de Pointes, clinically important atrial or ventricular arrhythmias (including sustained ventricular tachyarrhythmia and ventricular fibrillation), serious conduction system abnormalities (eg, bifascicular block defined as right bundle branch and left anterior or posterior hemiblock, 3rd degree AV block), unstable angina, coronary/peripheral artery bypass graft, symptomatic CHF, New York Heart Association class III or IV, cerebrovascular accident, transient ischemic attack, symptomatic pulmonary embolism, and/or other clinical significant episode of thrombo-embolic disease. Ongoing cardiac dysrhythmias of NCI CTCAE ≥ Grade 2, atrial fibrillation of any grade (≥ Grade 2 in the case of asymptomatic lone atrial fibrillation). If a participant has a cardiac rhythm device/pacemaker placed and QTcF >470 ms, the participant may be considered eligible. Participants with cardiac rhythm device/pacemaker must be discussed in detail with the sponsor to judge eligibility.

Other Exclusion Criteria:

13. Investigator site staff directly involved in the conduct of the study and their family members, site staff otherwise supervised by the investigator, and sponsor and sponsor delegate employees directly involved in the conduct of the study and their family members.