Each potential subject must satisfy all of the following criteria to be enrolled in the study: 1. e"18 years of age. 2. Criterion modified per Amendment 11 2.1. Documented initial diagnosis of multiple myeloma according to IMWG diagnostic a criteria. 3. Criterion modified per Amendment 1 3.1. Criterion modified per Amendment 11 Measurable disease Cohort A and Cohort B: Multiple myeloma must be measurable by central laboratory assessment: o Serum monoclonal paraprotein (M-protein) level e"1.0 g/dL or urine Mprotein level e"200 mg/24 hours, or o Light chain multiple myeloma without measurable disease in the serum or the urine: Serum immunoglobulin free light chain (FLC) e"10 mg/dL and abnormal serum immunoglobulin kappa lambda FLC ratio. If central laboratory assessments are not available, relevant local laboratory measurements must exceed the minimum required level by at least 25%. Prior treatment o Cohort A: have previously received e"3 prior lines of therapy that included at least one PI, one IMiD, and an anti-CD38 monoclonal antibody, and have not been exposed to T cell redirection therapies such as CAR-T or bispecific antibodies. o Cohort B: have previously received e"3 prior lines of therapy that included at least one PI, one IMiD, and an anti-CD38 monoclonal antibody, and have been exposed to T cell redirection therapies such as CAR-T or bispecific antibodies. Cohorts A and B: Undergone at least 1 complete cycle of treatment for each line of therapy, unless progressive disease was the best response to the line of therapy. Subject must have documented evidence of progressive disease based on investigator s determination of response by the IMWG 2016 criteria on or within 12 months of their last line of therapy. Also, subjects with documented evidence of progressive disease (as above) within the previous 6 months and who are refractory or non-responsive to their most recent line of therapy afterwards are eligible. Note: Refractory disease is defined as either <25% reduction in M-protein or confirmed progressive disease by IMWG criteria during previous treatment or 60 days after cessation of treatment. A single line of therapy may consist of 1 or more agents, and may include induction, hematopoietic stem cell transplantation, and maintenance therapy. Radiotherapy, bisphosphonate, or a single short course of corticosteroids (no more than the equivalent of dexamethasone 40 mg/day for 4 days) would not be considered prior lines of therapy. See Section 8.1 regarding prior treatment with anti CD38 therapies. 4. Criterion modified per Amendment 11 4.1. Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1. 5. Criterion modified per Amendment 1 5.1. Criterion modified per Amendment 9 5.2. Criterion modified per Amendment 11 5.3. Clinical laboratory values at screening: Hemoglobin e"8.0 g/dL (e"5 mmol/L) (must be without red blood cell [RBC] transfusion within 7 days prior to the laboratory test, recombinant human erythropoietin use is permitted) Platelets e"50×10^9/L (must be without transfusion support or platelet-stimulating factor in the 7 days prior to the laboratory test) Absolute Neutrophil Count (ANC) e"1.0×10^9/L (prior growth factor support is permitted but must be without support in the 7 days prior to the laboratory test) Aspartate Aminotransferase or Alanine Aminotransferase d"3.0 × upper limit of normal (ULN) Creatinine Clearance e"40 mL/min/1.73 m2 based upon Modified Diet in Renal Disease formula calculation. OR Serum creatinine: d"1.5 mg/dL Total bilirubin d"2.0 × ULN, except in subjects with congenital bilirubinemia, such as Gilbert syndrome (in which case direct bilirubin d"1.5 × ULN is required) Corrected serum calcium d"14 mg/dL (d"3.5 mmol/L) or free ionized calcium d"6.5 mg/dL (d"1.6 mmol/L). 6. Criterion modified per Amendment 10 6.1. Criterion modified per Amendment 11 6.2. Women of childbearing potential (WOCBP) (see Attachment 16) must have a negative pregnancy test at screening and prior to the first dose of study drug using a highly sensitive pregnancy test either serum (² human chorionic gonadotropin [²-hCG]) or urine. o a woman is considered of childbearing potential (WOCBP) (ie, fertile, following menarche and until becoming postmenopausal unless permanently sterile. Permanent sterilization methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy. 7. Criterion modified per Amendment 11: 7.1. Before the first dose of study drug: Women of childbearing potential and fertile men who are sexually active must agree to use a highly effective method of contraception (<1% / year failure rate) from the time of signing the informed consent form (ICF) during the study and for 100 days after the last dose of study drug. Contraception must be consistent with local regulations regarding the use of birth control methods for subjects participating in clinical trials. When a woman is of childbearing potential the following are required: o subject must agree to practice a highly effective method of contraception (failure rate of <1% per year when used consistently and correctly). Examples of highly effective contraceptives include: o user-independent methods: implantable progestogen-only hormone contraception associated with inhibition of ovulation, intrauterine device, intrauterine hormone-releasing system, vasectomized partner, o user-dependent methods: combined (estrogen- and progestogen-containing) hormonal contraception associated with inhibition of ovulation: oral, intravaginal, and transdermal, progestogen-only hormone contraception associated with inhibition of ovulation: oral and injectable ¨ð A woman using oral contraceptives must use an additional barrier method. In addition to the highly effective method of contraception, a man: o who is sexually active with a woman of childbearing potential must agree to use a barrier method of contraception (eg, condom with spermicidal foam/gel/film/cream/suppository) o who is sexually active with a woman who is pregnant must use a condom Women and men must agree not to donate eggs (ova, oocytes) or sperm, respectively, during the study and for 100 days after the last dose of study drug. Note: If the childbearing potential changes after start of the study or the risk of pregnancy changes, a woman must begin a highly effective method of contraception, as described throughout the inclusion criteria. If reproductive status is questionable, additional evaluation should be considered. It should be noted that interaction between hormonal contraception and talquetamab have not been studied. Therefore, it is unknown whether talquetamab may reduce the efficacy of the contraceptive method. 8. Sign an ICF indicating that he or she understands the purpose of and procedures required for the study and is willing to and able participate in the study. Consent is to be obtained prior to the initiation of any study-related tests or procedures that are not part of standard of care for the subject s disease. 9. Willing and able to adhere to the prohibitions and restrictions specified in this protocol.

Any potential subject who meets any of the following criteria will be excluded from participating in the study: 1. Criterion modified per Amendment 11. 1.1. Prior Grade 3 CRS (Per Lee Criteria 201426, Attachment 5) related to any T cell redirection (eg, CD-3 redirection technology or CAR-T cell therapy) or any prior GPRC5D targeting therapy. 2. Criterion modified per Amendment 10. 2.1. Criterion modified per Amendment 11 2.2. Prior antitumor therapy as follows, prior to the first dose of study drug: o Gene modified adoptive cell therapy (eg, chimeric antigen receptor modified T cells [CAR-T], natural killer [NK] cells) within 3 months. o Targeted therapy, epigenetic therapy, or treatment with an investigational drug or an invasive investigational medical device within 21 days or at least 5 half-lives, whichever is less. o Monoclonal antibody treatment for multiple myeloma within 21 days. o Cytotoxic therapy within 21 days. o Proteasome inhibitor therapy within 14 days. o Immunomodulatory agent therapy within 7 days. o Radiotherapy within 14 days. However, if palliative focal radiation is used, the subject is eligible irrespective of the end date of radiotherapy. Part 3 only: o Cohort A only: exposed to a CAR-T or T cell redirection therapy at any time. o Cohort B: T cell redirection therapy within 3 months 3. Criterion modified per Amendment 11 3.1. Vaccinated with live, attenuated vaccine within 4 weeks or as recommended by the product manufacturer prior to the first dose, during treatment, or within 100 days of the last dose of talquetamab. 4. Toxicities from previous anticancer therapies should have resolved to baseline levels or to Grade 1 or less except for alopecia or peripheral neuropathy. 5. Criterion modified per Amendment 11. 5.1. Received a cumulative dose of corticosteroids equivalent to e"140 mg of prednisone within the 14-day period before the first dose of study drug (does not include pretreatment medication). 6. Criterion modified per Amendment 6. 6.1. Received either of the following: o An allogenic stem cell transplant within 6 months before first dose of study drug. Subjects who received an allogeneic transplant must be off all immunosuppressive medications for 6 weeks without signs of graft versus host disease (GVHD). o An autologous stem cell transplant d"12 weeks before first dose of study drug. 7. Criterion modified per Amendment 9. 7.1 Central nervous system (CNS) involvement or clinical signs of meningeal involvement of multiple myeloma. If either is suspected, negative whole brain magnetic resonance imaging (MRI) and lumbar cytology are required. 8. Criterion modified per Amendment 6 8.1. Criterion modified per Amendment 11 8.2. Plasma cell leukemia (>2.0 x 10^9/L plasma cells by standard differential), Waldenström s macroglobulinemia, POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein [M-protein], and skin changes), or primary amyloid light chain amyloidosis. 9. Known to be seropositive for human immunodeficiency virus or acquired immune deficiency syndrome. 10. Criterion modified per Amendment 11 10.1. Hepatitis B infection as defined according to the American Society of Clinical Oncology guidelines. In the event the infection status is unclear, quantitative levels are necessary to determine the infection status (Attachment 14).2,18 Active Hepatitis C infection as measured by positive HCV-RNA testing. Subjects with a history of Hepatitis C virus antibody positivity must undergo HCV-RNA testing. 11. Pulmonary compromise requiring supplemental oxygen use to maintain adequate oxygenation. 12. Criterion modified per Amendment 11 12.1. Known allergies, hypersensitivity, or intolerance to talquetamab or its excipients (refer to Investigator s Brochure). 13. Criterion modified per Amendment 8. 13.1. Criterion modified per Amendment 11 13.2. Any serious underlying medical condition, such as: o Evidence of serious active viral, bacterial, or uncontrolled systemic fungal infection o Active autoimmune disease or a documented history of autoimmune disease, with the exception of vitiligo, resolved childhood atopic dermatitis, and prior Grave s disease that is currently euthyroid based on clinical symptoms and laboratory testing. o Psychiatric conditions (eg, alcohol or drug abuse), severe dementia, or altered mental status o Any other issue that would impair the ability of the subject to receive or tolerate the planned treatment at the investigational site, to understand informed consent or any condition for which, in the opinion of the investigator, participation would not be in the best interest of the subject (eg, compromise the well-being) or that could prevent, limit, or confound the protocol-specified assessments. 14. Pregnant, breastfeeding, or planning to become pregnant while enrolled in this study or within 100 days after the last dose of study drug. 15. Plans to father a child while enrolled in this study or within 100 days after the last dose of study drug. 16. Major surgery within 2 weeks of the first dose, or will not have fully recovered from surgery, or has surgery planned during the time the subject is expected to participate in the study or within 2 weeks after the last dose of study drug administration (Note: subjects with planned surgical procedures to be conducted under local anesthesia may participate). Any potential subject who meets any of the following criteria will be excluded from participating in Part 3: 17. Criterion added per Amendment 11 Stroke or seizure within 6 months prior to signing the ICF. 18. Criterion added per Amendment 11 The following cardiac conditions: o New York Heart Association Stage III or IV congestive heart failure o Myocardial infarction or coronary artery bypass graft (CABG) d"6 months prior to enrollment o History of clinically significant ventricular arrhythmia or unexplained syncope, not believed to be vasovagal in nature or due to dehydration o History of severe non-ischemic cardiomyopathy. 19. Criterion added per Amendment 11 Active malignancies (ie, progressing or requiring treatment change in the last 24 months) other than the disease being treated under study. The only allowed exceptions are: o Non-muscle invasive bladder cancer. o Skin cancer (non-melanoma or melanoma) treated within the last 24 months that is considered completely cured. o Noninvasive cervical cancer treated within the last 24 months that is considered completely cured. o Localized prostate cancer (N0M0): §ð With a Gleason score of 6, treated within the last 24 months or untreated and under surveillance. §ð With a Gleason score of 3+4 that has been treated more than 6 months prior to full study screening and considered to have a very low risk of recurrence, §ð Or history of localized prostate cancer and receiving androgen deprivation therapy and considered to have a very low risk of recurrence. o Breast cancer: §ð Adequately treated lobular carcinoma in situ or ductal carcinoma in situ, §ð Or history of localized breast cancer and receiving antihormonal agents and considered to have a very low risk of recurrence. o Malignancy that is considered cured with minimal risk of recurrence. NOTE: Investigators should ensure that all study inclusion/exclusion criteria have been met at screening and prior to the first dose of study drug. If a subject s clinical status changes (including any available laboratory results or receipt of additional medical records) after screening but before the first dose of study drug is given such that he or she no longer meets all eligibility criteria, supportive treatment may be administered according to local standards of care, if necessary, so that eligibility criteria may be met and laboratory test(s) may be repeated once, to determine if the subject qualifies for the study. If inclusion/exclusion criteria are not met after further evaluation, the subject should be excluded from participation in the study. Section 9.1.2 describes options for retesting. Section 17.4, describes the required documentation to support meeting the enrollment criteria.