Efficacy and Safety Study of bb2121 Versus Standard Triplet Regimens in Subjects With Relapsed and Refractory Multiple Myeloma (RRMM)

Inclusion Criteria:

Subjects must satisfy the following criteria to be enrolled in the study:

1. Subject is ≥ 18 years of age at the time of signing the informed consent form (ICF).

2. Subject has documented diagnosis of MM and measurable disease, defined as:

- M-protein (serum protein electrophoresis [sPEP] or urine protein electrophoresis
[uPEP]): sPEP ≥ 0.5 g/dL or uPEP ≥ 200 mg/24 hours and/or

- Light chain MM without measurable disease in the serum or urine: Serum
immunoglobulin free light chain ≥ 10 mg/dL (100 mg/L) and abnormal serum
immunoglobulin kappa lambda free light chain ratio

3. Subject has received at least 2 but no greater than 4 prior MM regimens.

4. Subject has received prior treatment with DARA, a proteasome inhibitor- and an
immunomodulatory compound-containing regimen for at least 2 consecutive cycles.

5. Subject must be refractory to the last treatment regimen. Refractory is defined as
documented progressive disease during or within 60 days (measured from the last dose
of any drug within the regimen) of completing treatment with the last anti-myeloma
regimen before study entry.

6. Subject achieved a response (minimal response [MR] or better) to at least 1 prior
treatment regimen.

7. Subject has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

8. Recovery to Grade 1 or baseline of any non-hematologic toxicities due to prior
treatments, excluding alopecia and Grade 2 peripheral neuropathy.

Exclusion Criteria:

The presence of any of the following will exclude a subject from enrollment:

1. Subject has nonsecretory multiple myeloma (MM).

2. Subject has any of the following laboratory abnormalities:

1. Absolute neutrophil count (ANC) < 1,000/μL

2. Platelet count: < 75,000/μL in subjects in whom < 50% of bone marrow nucleated
cells are plasma cells and platelet count < 50,000/μL in subjects in whom ≥ 50%
of bone marrow nucleated cells are plasma cells (it is not permissible to
transfuse a subject to reach this level)

3. Hemoglobin < 8 g/dL (< 4.9 mmol/L) (it is not permissible to transfuse a subject
to reach this level)

4. Serum creatinine clearance (CrCl) < 45 mL/min

5. Corrected serum calcium > 13.5 mg/dL (> 3.4 mmol/L)

6. Serum aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 2.5 ×
upper limit of normal (ULN)

7. Serum total bilirubin > 1.5 × ULN or > 3.0 mg/dL for subjects with documented
Gilbert's syndrome

8. International normalized ratio (INR) or activated partial thromboplastin time
(aPTT) > 1.5 × ULN, or history of Grade ≥ 2 hemorrhage within 30 days, or subject
requires ongoing treatment with chronic, therapeutic dosing of anticoagulants
(eg, warfarin, low molecular weight heparin, Factor Xa inhibitors)

3. Subject has inadequate pulmonary function defined as oxygen saturation (SaO2) < 92% on
room air.

4. Subject has prior history of malignancies, other than MM, unless the subject has been
free of the disease for ≥ 5 years

5. Subject has active or history of plasma cell leukemia, Waldenstrom's
macroglobulinemia, POEMS syndrome or amyloidosis.

6. Subject with known central nervous system (CNS) involvement with myeloma.

7. Subject has clinical evidence of pulmonary leukostasis and disseminated intravascular
coagulation.

8. Subject has known chronic obstructive pulmonary disease (COPD) with a forced
expiratory volume in 1 second (FEV1) 50% of predicted normal.

9. Subject has a history or presence of clinically relevant CNS pathology.

10. Subject was treated with DARA in combination with POM with or without dex (DP±d) as
part of their most recent anti-myeloma treatment regimen, cannot receive DPd as
bridging therapy but may receive DVd or IRd as bridging as per Investigator's
discretion if randomized to Treatment Arm A.

11. Subject was treated with DP±d as part of their most recent anti-myeloma treatment
regimen, cannot receive DPd if randomized to Treatment Arm B but may receive DVd or
IRd as per Investigator's discretion.

12. Subject was treated with DARA in combination with BTZ with or without dex (DV±d) as
part of their most recent anti-myeloma treatment regimen, cannot receive DVd as
bridging therapy but may receive DPd or IRd as bridging as per Investigator's
discretion if randomized to Treatment Arm A.

13. Subject was treated with DV±d as part of their most recent anti-myeloma treatment
regimen, cannot receive DVd if randomized to Treatment Arm B but may receive DPd or
IRd as per Investigator's discretion.

14. Subject was treated with IXA in combination with LEN with or without dex (IR±d) as
part of their most recent anti-myeloma treatment regimen, cannot receive IRd as
bridging therapy but may receive DPd or DVd as bridging as per Investigator's
discretion if randomized to Treatment Arm A.

15. Subject was treated with IR±d as part of their most recent anti-myeloma treatment
regimen, cannot receive IRd if randomized to Treatment Arm B but may receive DPd or
DVd as per Investigator's discretion.

16. Previous history of an allogeneic hematopoietic stem cell transplantation, treatment
with any gene therapy-based therapeutic for cancer, investigational cellular therapy
for cancer or BCMA targeted therapy.

17. Subject has received autologous stem cell transplantation (ASCT) within 12 weeks prior
to randomization.

18. Subject has received any of the following within the last 14 days prior to
randomization:

1. Plasmapheresis

2. Major surgery (as defined by the Investigator)

3. Radiation therapy other than local therapy for myeloma-associated bone lesions

4. Use of any investigational agents and systemic anti-myeloma drug therapy

19. Echocardiogram (ECHO) or multigated acquisition (MUGA) with left ventricular ejection
fraction (LVEF) < 45%.

21. Subject is positive for human immunodeficiency virus (HIV-1), chronic or active
hepatitis B or active hepatitis A or C.

22. Subject has uncontrolled systemic fungal, bacterial, viral or other infection (defined
as exhibiting ongoing signs/symptoms related to the infection and without improvement,
despite appropriate antimicrobial treatment) or requiring IV antimicrobials for management.

23. Subject has a history of class III or IV congestive heart failure (CHF) or severe
nonischemic cardiomyopathy, unstable or poorly controlled angina, myocardial infarction, or
ventricular arrhythmia within the previous 6 months prior to randomization.

24. Hypersensitivity to DARA, thalidomide, lenalidomide, POM, BTZ, IXA or dex. This
includes rash ≥ Grade 3 during prior thalidomide, POM or lenalidomide therapy.

25. Subject with known hypersensitivity to any component of bb2121 product,
cyclophosphamide, fludarabine, and/or tocilizumab or hypersensitivity to the excipients
contained in the formulation of DARA, POM, LEN, IXA, BTZ or dex.

26. Subject is a female who is pregnant, nursing, or breastfeeding 27. For a subject
randomized to Treatment Arm B and will be on a POM- or LEN-containing regimen; unable or
unwilling to undergo protocol required thromboembolism prophylaxis.

28 Subject is intolerant to bortezomib, subject cannot receive DVd as bridging therapy if
randomized.