Outpatient Administration of Teclistamab or Talquetamab for Multiple Myeloma

Inclusion Criteria:

• Be ≥18 years of age (or the higher legal age in the jurisdiction in which the studyis taking place) at the time of informed consent

• Has documented diagnosis of MM according to the IMWG diagnostic criteria (Rajkumar 2011).

• Has received 2 or more prior MM therapies including a PI, IMiD and CD38 antibody.

• Has an ECOG performance status (Oken 1982) of 0 to 1.

• Measurable disease at screening, as assessed by local laboratory, defined by any ofthe following:

• Serum M-protein level ≥0.5 g/dL; or

• Urine M-protein level ≥200 mg/24 hours; or

• Light chain MM without measurable M-protein in the serum or the urine: serumfree light chain (sFLC) ≥10 mg/dL and abnormal serum immunoglobulin kappalambda FLC ratio.

• For participants without measurable disease in the serum, urine, or involvedFLC, presence of plasmacytomas (≥2 cm).

• Human immunodeficiency virus-positive participants are eligible if they meet all ofthe following:

• No detectable viral load (i.e., <50 copies/mL) at screening

• CD4+ count >300 cells/mm3 at screening

• No acquired immunodeficiency syndrome (AIDS)-defining opportunistic infectionwithin 6 months of screening

• Receiving highly active antiretroviral therapy (HAART). Any changes in HAARTdue to resistance/progression should occur at least 3 months prior toenrollment. A change in HAART due to toxicity is allowed up to 4 weeks prior toenrollment.

• Adequate organ system function

• Body weight >35 kg.

• A participant of childbearing potential must have a negative highly sensitive serum (β-hCG) at screening and within 72 hours of the start of study treatment and mustagree to further serum or urine pregnancy tests during the study.

• A participant must agree to abide by protocol defined contraceptive requirements forthe duration of the study

• A participant must sign an ICF indicating that participant understands the purposeof, and procedures required for, the study and is willing to participate in thestudy.

• A participant is required to stay within 30 minutes of transportation to the siteand remain in the company of a competent adult at all times until 48 hours followingadministration of all doses within the teclistamab or talquetamab step-up dosingschedule

• A participant must agree to carry the study participant identification wallet cardat all times.

• A participant must comply with all the protocol requirement procedures, includingmeasuring and recording of body temperature and blood oxygen saturation twice daily (≥8 hours apart) during the first 2 cycles of teclistamab or talquetamab treatmentand coming to the study site for safety assessments.

• A participant and the accompanying competent adult must be made aware of thepresenting sign sand symptoms of teclistamab- or talquetamab- associated toxicities,including but not limited to CRS, ICANS, infections, etc. The accompanying competentadult must watch the participant at all times for teclistamab- or talquetamab-associated toxicities, until 48 hours after the first treatment dose of teclistamabor talquetamab.

Exclusion Criteria:

• Has high tumor burden, defined as having ≥60% plasma cell infiltrate on the bonemarrow biopsy or aspirate, whichever is higher, or with multiple extramedullarydisease sites or plasmacytomas.

• Has a rapidly progressing disease per investigator assessment.

• Has plasma cell leukemia (>2.0×10^9/L plasma cells by standard differential),Waldenström's macroglobulinemia, POEMS syndrome (polyneuropathy, organomegaly,endocrinopathy, monoclonal protein, and skin changes), or primary amyloidlight-chain amyloidosis.

• Has known active CNS involvement or exhibits clinical signs of meningeal involvementof MM.

• Has risk factors for developing clinically significant TLS and requiring managementwith increased hydration, allopurinol, or rasburicase.

• Has myelodysplastic syndrome or active malignancies (ie, progressing or requiringtreatment change in the last 12 months) other than RRMM. The only allowed exceptionsare:

• Any malignancy that was not progressing nor requiring treatment change in thelast 12 months.

• Malignancies treated within the last 12 months and considered at very low riskfor recurrence:

• Non-muscle invasive bladder cancer (solitary Ta-PUNLMP or low grade, <3 cm, noCIS).

• Skin cancer (non-melanoma or melanoma).

• Noninvasive cervical cancer.

• Breast cancer: adequately treated lobular carcinoma in situ or ductal carcinomain situ, localized breast cancer and receiving antihormonal agents.

• Localized prostate cancer (M0, N0) with a Gleason Score ≤7a, treated locallyonly (RP/RT/focal treatment).

• Other malignancy that is considered at minimal risk of recurrence.

• Has Grade ≥3 hematologic AEs or Grade ≥3, clinically significant non-hematologicAEs.

• Has fever or active infection (bacterial, viral, or uncontrolled systemic fungal) attime of study enrollment.

• Has active autoimmune disease or a documented history of autoimmune disease with theexception of vitiligo, type I diabetes, and prior autoimmune thyroiditis that iscurrently euthyroid based on clinical symptoms and laboratory testing.

• Has clinically significant coagulopathy that would increase the risk of bleeding inthe setting of cytopenia.

• Shows a deterioration in neurologic status, including mental status changes such asconfusion or increased somnolence.

• Has psychiatric disorders (eg, alcohol or drug abuse), dementia, or altered mentalstatus that would compromise the ability to provide informed consent or comply withthe clinical protocol.

• History of stroke, transient ischemic attack or seizure within 6 months of signingICF.

• Presence of the following cardiac conditions:

• New York Heart Association stage III or IV congestive heart failure.

• Myocardial infarction or CABG ≤6 months prior to enrollment.

• History of clinically significant ventricular arrhythmia or unexplainedsyncope, not believed to be vasovagal in nature or due to dehydration.

• History of severe non-ischemic cardiomyopathy.

• Poorly controlled coronary artery disease and/or congestive heart failure.

• Uncontrolled cardiac arrhythmia or clinically significant ECG abnormalities.

• Has hepatitis B infection (ie, HBsAg or HBV-DNA positive). In the event theinfection status is unclear, quantitative viral levels are necessary to determinethe infection status.

• Has active hepatitis C infection as measured by positive HCV-RNA testing.Participants with a history of HCV antibody positivity must undergo HCV-RNA testing.If a participant with history of chronic hepatitis C infection (defined as both HCVantibody and HCV-RNA positive) completed antiviral therapy and has undetectableHCV-RNA 12 weeks following the completion of therapy, the participant is eligiblefor the study.

• Has COPD with FEV1 <50% of predicted.

• Has eGFR <20 ml/min or is dependent on dialysis.

• Has other medical issue that would impair the ability of the participant to receiveor tolerate the planned treatment at the investigational site, to understandinformed consent or any condition for which, in the opinion of the investigator,participation would not be in the best interest of the participant (eg, compromisethe well-being) or that could prevent, limit, or confound the protocol-specifiedassessments.

• For talquetamab arm only: Prior Grade 3 or higher CRS related to any T-cellredirection (e.g., CD-3 redirection technology or CAR-T cell therapy), or any priorGPRC5D-targeting therapy.

• Has received packed RBC or platelet transfusions within the last 7 days prior todosing.

• Has contraindications to the use of tocilizumab or IVIG per local prescribinginformation.

• Has received live vaccine(s) within 1 month prior to screening or plans to receivelive vaccines during the study.

• Has received live, attenuated vaccine within 30 days before the first dose ofteclistamab or talquetamab. Live, attenuated influenza vaccines are permitted aslate as 30 days before the study treatment.

• Has received an investigational intervention or used an invasive investigationalmedical device within 14 days before the planned first dose of study treatment orreceived an investigational biological product within 14 days or 5 half-lives,whichever is longer, before the planned study treatment, or is currently enrolled inan investigational study.

• History of antitumor therapy as follows, before the first dose of study drug:

• Targeted therapy, epigenetic therapy, or treatment with an investigational drugor used an invasive investigational medical device within 21 days or at least 5half-lives, whichever is less.

• Monoclonal antibody treatment for MM within 21 days.

• Cytotoxic therapy within 21 days.

• PI therapy within 14 days.

• Immunomodulatory agent therapy within 7 days.

• For teclistamab arm only: Prior Ggene modified adoptive cell therapy (eg,chimeric antigen receptor modified [CAR]-T cells, NK cells) within 3 months. orBCMA therapy).

• Radiotherapy within 14 days or focal radiation within 7 days.

• For talquetamab arm only: Prior CAR-T or BCMAbispecific antibody therapy areallowed.

• History of stem cell transplant:

• An allogeneic stem cell transplant within 6 months. Participants who receivedan allogeneic transplant must be off all immunosuppressive medications for ≥42days without signs of graft-versus-host disease.

• An autologous stem cell transplant ≤12 weeks before the first dose of studydrug.