Bortezomib, Selinexor, and Dexamethasone in Patients With Multiple Myeloma

Inclusion Criteria:

1. Histologically confirmed MM with measurable disease per IMWG guidelines as defined by
at least 1 of the following:

1. Serum M-protein ≥ 0.5 g/dL (> 5 g/L) by serum protein electrophoresis (SPEP) or
for immunoglobulin (Ig) A myeloma, by quantitative serum IgA levels; or

2. Urinary M-protein excretion at least 200 mg/24 hours; or

3. Serum free light chain (FLC) ≥ 100 mg/L, provided that the serum FLC ratio is
abnormal.

2. Had at least 1 prior anti-MM regimen and no more than 3 prior anti-MM regimens.
Induction therapy followed by stem cell transplant and consolidation/maintenance
therapy will be considered as 1 anti-MM regimen.

3. Documented evidence of progressive MM (based on the Investigator's determination
according to the modified IMWG response criteria) on or after their most recent
regimen.

4. Prior treatment with bortezomib or other Proteasome Inhibitor (PI) is allowed,
provided all of the following criteria are met:

- Best response achieved with prior bortezomib at any time was ≥ PR and with the
last PI (PI therapy (alone or in combination) was ≥ PR, AND

- Participant did not discontinue bortezomib due to ≥ Grade 3 related toxicity, AND

- Must have had at least a 6-month PI-treatment-free interval prior to Cycle 1 Day
1 (C1D1) of study treatment.

5. Must have an ECOG Status score of 0, 1, or 2.

6. Written informed consent in accordance with federal, local, and institutional
guidelines.

7. Age ≥18 years.

8. Resolution of any clinically significant non-hematological toxicities (if any) from
previous treatments to ≤ Grade 1 by C1D1.

9. Adequate hepatic function within 28 days prior to C1D1.

10. Adequate renal function within 28 days prior to C1D1.

11. Adequate hematopoietic function within 7 days prior to C1D1.

12. Female patients of childbearing potential must have a negative serum pregnancy test at
Screening. Female patients of childbearing potential and fertile male patients who are
sexually active with a female of childbearing potential must use highly effective
methods of contraception throughout the study and for 3 months following the last dose
of study treatment.

Exclusion Criteria:

1. Prior exposure to a SINE compound (i.e. an XPO-1 inhibitor), including selinexor.

2. Prior malignancy that required treatment, or has shown evidence of recurrence (except
for non-melanoma skin cancer or adequately treated cervical carcinoma in situ) during
the 5 years prior to randomization.

3. Any concurrent medical condition or disease (e.g., uncontrolled active hypertension,
uncontrolled active diabetes, active systemic infection, etc.) that is likely to
interfere with study procedures.

4. Uncontrolled active infection requiring parenteral antibiotics, antivirals, or
antifungals within 1 week prior to C1D1.

5. Active plasma cell leukemia.

6. Documented systemic light chain amyloidosis.

7. MM involving the central nervous system.

8. Polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes
(POEMS) syndrome.

9. Spinal cord compression.

10. Greater than Grade 2 neuropathy or ≥ Grade 2 neuropathy with pain at baseline,
regardless of whether or not the patient is currently receiving medication

11. Known intolerance, hypersensitivity, or contraindication to glucocorticoids.

12. Radiation, chemotherapy, or immunotherapy or any other anticancer therapy (including
investigational therapies) ≤ 2 weeks prior to C1D1. Localized radiation to a single
site at least 1 week before C1D1 is permitted. Glucocorticoids within 2 weeks of C1D1
are permitted. Patients on long-term glucocorticoids during Screening do not require a
washout period but must be able to tolerate the specified dexamethasone dose in this
study.

13. Prior autologous stem cell transplantation < 1 month or allogeneic stem cell
transplantation < 4 months prior to C1D1.

14. Active graft versus host disease (after allogeneic stem cell transplantation) at C1D1.

15. Pregnant or breastfeeding females.

16. Body Surface Area < 1.4 m² at baseline, calculated by the Dubois or Mosteller method.

17. Life expectancy of < 4 months.

18. Major surgery within 4 weeks prior to C1D1.

19. Active, unstable cardiovascular function:

1. Symptomatic ischemia, or

2. Uncontrolled clinically significant conduction abnormalities (e.g., patients with
ventricular tachycardia on anti-arrhythmics are excluded; patients with
first-degree atrioventricular block or asymptomatic left anterior fascicular
block/right bundle branch block will not be excluded), or

3. Congestive heart failure of New York Heart Association Class ≥ 3 or known left
ventricular ejection fraction < 40%, or

4. Myocardial infarction within 3 months prior to C1D1.

20. Known active human immunodeficiency virus (HIV) infection or HIV seropositivity

21. Known active hepatitis A, B, or C infection; or known to be positive for hepatitis C
virus ribonucleic acid (RNA) or hepatitis B virus surface antigen.

22. Any active gastrointestinal dysfunction interfering with the patient's ability to
swallow tablets, or any active gastrointestinal dysfunction that could interfere with
absorption of study treatment.

23. Any active, serious psychiatric, medical, or other conditions/situations that, in the
opinion of the Investigator, could interfere with treatment, compliance, or the
ability to give informed consent.

24. Contraindication to any of the required concomitant drugs or supportive treatments.

25. Patients unwilling or unable to comply with the protocol, including providing 24-hour
urine samples for urine protein electrophoresis at the required time points.