Cevostamab Following CAR T Cell Therapy for RRMM

Inclusion Criteria:

1. Signed Informed Consent Form(s)

2. Age ≥18 years at time of signing Informed Consent Form

3. Ability to comply with the study protocol

4. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1

5. Life expectancy of at least 12 weeks

6. Participants must have relapsed and/or refractory multiple myeloma with therapy thatmust include a proteasome inhibitor, immunomodulatory drug (IMiD), and anti-CD38antibody, and have received a BCMA-directed CAR T cell product as standard of care (i.e. not on a clinical trial) as per the current FDA label, between 6 and 10 weeksprior to enrollment, and have not had progressive disease by IMWG criteria since CART cell infusion. Patients who have received out-of-specification CAR T cell productsare not eligible.

7. For patients who received ide-cel, they must have had at least 2 prior lines oftherapy prior to ide-cel

8. For patients who received cilta-cel, they must have had at least 2 prior linesprior to cilta-cel, or 1 prior line and be refractory or intolerant tolenalidomide.

9. Agreement to provide bone marrow biopsy and aspirate samples

10. Non-hematologic adverse events from prior anti-cancer therapy resolved to Grade ≤ 1,with the certain exceptions.

11. Measurable disease is not required for study entry

12. Laboratory values as follows: a. Hepatic function i. AST and ALT ≤ 3 x ULN ii. Total bilirubin ≤ 1.5 x ULN; b.Hematologic function (cevostamab criteria should be met both at screening (todetermine eligibility), as well as on Cycle1, Day 1) i. Platelet count ≥ 50,000/mm3without transfusion within 7 days prior to first dose ii. ANC ≥ 1000/mm3 iii. Totalhemoglobin ≥ 7 g/dL c. Creatinine clearance (CrCl) ≥ 30 mL/min d. Serum calcium (corrected for albumin) level at or below Grade 1 hypercalcemia

13. For women of childbearing potential: agreement to remain abstinent (refrain fromheterosexual intercourse) or use contraceptive measures, as defined in the protocol.

14. For men: agreement to remain abstinent (refrain from heterosexual intercourse) oruse a condom, and agreement to refrain from donating sperm, as defined in theprotocol.

Exclusion Criteria:

1. Inability to comply with protocol-mandated hospitalization and activitiesrestrictions

2. Pregnant or breastfeeding, or intending to become pregnant during the study orwithin 3 months after the last dose of study drug a. Women of childbearing potential must have a negative serum pregnancy test resultwithin 14 days prior to initiation of study drug.

3. Participants who had ≥ Grade 3 cytokine release syndrome (CRS) or immune effectorcell-associated neurotoxicity syndrome (ICANS) by ASTCT criteria, or any grademacrophage activation syndrome/hemophagocytic lymphohistiocytosis (MAS/HLH)afterCAR-T therapy are excluded

4. Participants who had any grade movement and/or neurocognitive disorder attributed toCAR T cells are excluded.

5. Prior treatment with systemic immunotherapeutic agents, including, but not limitedto, cytokine therapy and anti-CTLA4, anti-PD-1, and anti-PD-L1 therapeuticantibodies, within 12 weeks or 5 half-lives of the drug, whichever is shorter,before first cevostamab infusion

6. Known treatment-related, immune-mediated adverse events associated with priorimmunotherapeutic agents as in the protocol.

7. Treatment with any chemotherapeutic agent, or any other anti-cancer agent (investigational or otherwise) during the time period between CAR T cell infusionand first cevostamab infusion, with the following exceptions:

8. Therapies used for treatment of CAR T cell-related toxicities (e.g. steroids,cyclophosphamide) will not be a cause for exclusion, as long as washout periodlisted below (2 weeks) is met

9. Short course palliative radiation post-CAR T cell therapy (e.g. for severe bonepain, impending fracture) is allowed as long as completed at least 1 week priorto first dose of cevostamab.

10. Received systemic immunosuppressive medications (including, but not limited to,steroids, cyclophosphamide, azathioprine, methotrexate, thalidomide, tocilizumab,siltuximab, anakinra, ruxolitinib, and anti-tumor necrosis factor agents), with theexception of corticosteroid treatment ≤ 10 mg/day prednisone or equivalent, within 2weeks prior to first dose of cevostamab a. Participants who received acute, low-dose, systemic immunosuppressant medications (e.g., single dose of dexamethasone for nausea) may be enrolled in the study. i. The use of inhaled corticosteroids is permitted. ii. The use ofmineralocorticoids for management of orthostatic hypotension is permitted. iii. The use of physiologic doses of corticosteroids for management of adrenalinsufficiency is permitted.

11. Autologous stem cell transplantation (SCT) within 100 days prior to first cevostamabinfusion

12. Prior allogeneic SCT within 12 months prior to first cevostamab infusion.Participants with prior allogeneic SCT must have no evidence for activegraft-versus-host-disease (GVHD) and be off all therapy for GVHD for at least 3months prior to first cevostamab infusion.

13. Prior solid organ transplantation

14. History of autoimmune disease, including, but not limited to, myasthenia gravis,myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis,inflammatory bowel disease, vascular thrombosis associated with antiphospholipidsyndrome, Wegener's granulomatosis, Sjögren's syndrome, Guillain-Barré syndrome,multiple sclerosis, vasculitis, or glomerulonephritis

15. Participants with a history of autoimmune-related hypothyroidism on a stabledose of thyroid replacement hormone may be eligible for this study.

16. Participants with history of immune thromobocytopenic purpura (ITP), autoimmunehemolytic anemia, or other immune-mediated conditions that solely affect bloodcounts, as long as these conditions are not active at the time of enrollmentand subjects otherwise meet hematologic parameters for eligibility, may beeligible with approval from Sponsor Medical Director.

17. Participants with history of confirmed progressive multifocal leukoencephalopathy

18. History of severe allergic or anaphylactic reactions to monoclonal antibody therapy (or recombinant antibody-related fusion proteins)

19. History of other malignancy that could affect compliance with the protocol orinterpretation of results

20. Participants with a history of curatively treated basal or squamous cellcarcinoma of the skin or in situ carcinoma of the cervix are allowed.

21. Participants with a malignancy that has been treated with curative intent willalso be allowed if the malignancy has been in remission prior to firstcevostamab infusion.

22. Current or past history of CNS disease, such as stroke, epilepsy, CNS vasculitis,neurodegenerative disease, or CNS involvement by MM

23. Participants with a history of stroke who have not experienced a stroke ortransient ischemic attack in the past 2 years and have no residual neurologicdeficits as judged by the investigator are allowed.

24. Participants with a history of epilepsy who have had no seizures in the past 2years while not receiving any anti-epileptic medications are allowed.

25. Significant cardiovascular disease (such as, but not limited to, New York HeartAssociation Class III or IV cardiac disease, myocardial infarction within the last 6months, uncontrolled arrhythmias, or unstable angina) that may limit a subject'sability to adequately tolerate a cytokine release syndrome (CRS) event

26. Symptomatic active pulmonary disease or requiring supplemental oxygen

27. Known active bacterial, viral, fungal, mycobacterial, parasitic, or other infection (excluding fungal infections of nail beds) at study enrollment, or any major episodeof infection requiring treatment with IV antibiotics within 14 days prior to firstcevostamab infusion. Empiric or prophylactic antibiotics administered duringneutropenia or neutropenic fever without microbiologic evidence of infection do notexclude subjects. a. Participants with asymptomatic CMV reactivation (i.e. positive CMV PCR) found atscreening may enroll after discussion with the Medical Director.

28. Known or suspected chronic active Epstein-Barr virus (EBV) infection. Guidelines fordiagnosing chronic active EBV infection are provided by Okano et al. (2005).

29. Recent major surgery within 4 weeks prior to first cevostamab infusion a. Protocol-mandated procedures (e.g., bone marrow biopsies) are permitted.

30. Positive serologic or polymerase chain reaction (PCR) test results for acute orchronic hepatitis B virus (HBV) infection a. Participants whose HBV infection status cannot be determined by serologic testresults must be negative for HBV by PCR to be eligible for study participation.

31. Acute or chronic hepatitis C virus (HCV) infection a. Participants who are positive for HCV antibody must be negative for HCV by PCR tobe eligible for study participation.

32. Known history of HIV seropositivity

33. Administration of a live, attenuated vaccine within 4 weeks before first cevostamabinfusion or anticipation that such a live attenuated vaccine will be required duringthe study

34. Influenza vaccination should be given during influenza season (approximatelyOctober to May in the Northern Hemisphere). Subjects must not receive live,attenuated influenza vaccine (e.g., FluMist®) at any time during the studytreatment period.

35. SARS-CoV-2 vaccines may be given in accordance with the approved/authorizedvaccine label and official/local immunization guidance. SARS-CoV-2 vaccinesmust not be administered within 1 week before first study treatment or duringCycle 1.

36. Investigators should review the vaccination status of potential study subjectsbeing considered for this study and follow the U.S. Centers for Disease Controland Prevention guidelines for adult vaccination with any other non-livevaccines intended to prevent infectious diseases prior to study.

37. Any medical condition or abnormality in clinical laboratory tests that, in theMedical Director's judgment, precludes the subject's safe participation in andcompletion of the study, or which could affect compliance with the protocol orinterpretation of results.