Ensayos clínicos

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. For Cohorts 1 and 2 only, participant has 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 and abnormal serum immunoglobulin
kappa lambda free light chain ratio

3. Subjects with one of the following cohort specific requirements:

Cohort 1 RRMM subjects with ≥ 3 prior anti-myeloma treatment regimens:

- Subject must have received at least 3 prior anti-myeloma treatment regimens.
Note: induction with or without hematopoietic stem cell transplant and with or
without maintenance therapy is considered a single regimen

- Subject must have undergone at least 2 consecutive cycles of treatment for each
regimen, unless PD was the best response to the regimen

- Subject must have received prior treatment with a proteasome inhibitor, an
immunomodulatory agent and an anti-CD38 antibody

- Subject has evidence of PD on or within 60 days of the most recent prior
treatment regimen

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

Cohort 2 subjects with 1 prior anti-myeloma treatment regimen:

- Subject must have received only 1 prior anti-myeloma treatment regimen. Note:
induction with or without hematopoietic stem cell transplant and with or without
maintenance therapy is considered a single regimen

- Subject must have the following HR factors:

- Early relapse defined as:

Cohort 2a: PD < 18 months since date of start of initial therapy. Initial therapy must
contain induction, ASCT (single or tandem) and lenalidomide containing maintenance.

Cohort 2b: PD < 18 months since date of start or initial therapy which must contain at
minimum, a proteasome inhibitor, an immunomodulatory agent and dexamethasone Cohort
2c: Subject must have received minimum 3 cycles of induction therapy which must
contain at minimum, a proteasome inhibitor, an immunomodulatory agent and
dexamethasone. Subjects must have had ASCT (single or tandem AND < VGPR (excluding PD)
at first assessment between 70 to 110 days after last ASCT, with initial therapy
without consolidation and maintenance. Cohort 3 participants with newly diagnosed MM
(NDMM) who received only induction and ASCT, without subsequent consolidation or
maintenance Subject with NDMM who have received only induction and ASCT, without
subsequent consolidation or maintenance Cohort 3

- With NDMM who have received only induction and ASCT, without subsequent
consolidation or maintenance

- Must have received 4 to 6 cycles of induction therapy which must contain at
minimum, a proteasome inhibitor and an immunomodulatory agent and must have had
single ASCT within 6 months prior to consent

- Must have achieved documented PR or VGPR at first post-ASCT assessment
approximately 100 days after ASCT and this response must be maintained at
screening

- Per Investigator's assessment, subject must be a candidate for single-agent
lenalidomide maintenance

4. Subject must have Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1

5. Subject must have recovery to Grade 1 or baseline of any non-hematologic toxicities
due to prior treatments, excluding alopecia and Grade 2 neuropathy

Exclusion Criteria:

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

1. Subject used any investigational agents within 14 days prior to leukapheresis or, for
Cohort 3, within 14 days prior to consent

2. Subject received any of the following within the last 14 days prior to leukapheresis
or, for Cohort 3, within 14 days prior to consent:

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 systemic anti-myeloma drug therapy

3. Subject with known central nervous system involvement with myeloma

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

5. History or presence of clinically relevant central nervous system (CNS) pathology

6. Subject with active or history of plasma cell leukemia, Waldenstrom's
macroglobulinemia, POEMS syndrome, or clinically significant amyloidosis

7. Inadequate organ function Subject with 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 starting study treatment

8. Ongoing treatment with chronic immunosuppressants

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

10. Subject has received ASCT within 12 weeks prior to leukapheresis

11. Subject has history of primary immunodeficiency

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

13. Subject has uncontrolled systemic fungal, bacterial, viral or other infection
(including tuberculosis) despite appropriate antibiotics or other treatment

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

15. Pregnant or lactating women

16. Subject with known hypersensitivity to any component of bb2121 product,
cyclophosphamide, fludarabine, and/or tocilizumab

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Eligibility last updated 8/24/22. Questions regarding updates should be directed to the study team contact.