Phase 1/2a Study of Cancer Vaccine to Treat Smoldering Multiple Myeloma

This is a dose escalation, phase 1/2a study to assess the safety and tolerability of
PVX-410, (a multi-peptide cancer vaccine), treatment regimen in patients with smoldering
multiple myeloma as a single agent and in combination with lenalidomide.. Approximately 22
patients will receive six (6) bi-weekly, subcutaneous injections of PVX-410 for a total of
twelve (12) weeks of treatment. Safety will be monitored throughout the study.
Tolerability, immunogenicity and clinical response will also be measured as described in the
protocol.

- Patient has confirmed clinical diagnosis of SMM according to a definition derived
from the International Myeloma Working Group (IMWG) definition: serum M-protein ≥3
g/dL or bone marrow clonal plasma cells (BMPC) >10%, or both, along with normal organ
and marrow function (CRAB) within 4 weeks before baseline.

- C: Absence of hypercalcemia, evidenced by a calcium <10.5 mg/dL.

- R: Absence of renal failure, evidenced by a creatinine <2.0 mg/dL or calculated
creatinine clearance (using the Modification of Diet in Renal Disease [MDRD] formula)
>50 mL/min.

- A: Absence of anemia, evidenced by a hemoglobin >10 g/dL.

- B: Absence of lytic bone lesions on standard skeletal survey.

- Patient is at higher than average risk of progression to active MM, defined as having
2 or more of the following features:

- Serum monoclonal (M)-protein ≥3 g/dL.

- BMPC >10%.

- Abnormal serum free light chain (FLC) ratio (0.26-1.65).

- Patient has a life expectancy of greater than 6 months

- Patient is human leukocyte antigen (HLA)-A2 positive.

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

- Patient has adequate bone marrow function, evidenced by a platelet count ≥75×109/L
and an absolute neutrophil count (ANC) ≥1.0×109/L within 2 weeks before baseline.

- Patient has adequate hepatic function, evidenced by a bilirubin ≤2.0 mg/dL and an
alanine transaminase (ALT), and aspartate transaminase (AST) ≤2.5× the upper limit of
normal (ULN) within 2 weeks before baseline.

- If of child-bearing potential, patient agrees to use adequate birth control measures
during study participation.

- If a female of child-bearing potential, patient has negative urine pregnancy test
results within 2 weeks before baseline and is not lactating.

- Patient (or his or her legally accepted representative) has provided written informed
consent to participate in the study.

Exclusion Criteria:

- Patient has symptomatic multiple myeloma, as defined by any of the following:

- Lytic lesions or pathologic fractures.

- Anemia (hemoglobin <10 g/dL).

- Hypercalcemia (corrected serum calcium >11.5 mg/dL).

- Renal insufficiency (creatinine >2 mg/dL).

- Other: symptomatic hyperviscosity, amyloidosis.

- Patient has a history of a prior malignancy within the past 5 years (excluding
resected basal cell carcinoma of the skin or in situ cervical cancer).

- Patient has abnormal cardiac status, evidenced by any of the following:

- New York Heart Association (NYHA) stage III or IV congestive heart failure (CHF).

- Myocardial infarction within the previous 6 months.

- Symptomatic cardiac arrhythmia requiring treatment or persisting despite treatment.

- Patient is receiving any other investigational agent.

- Patient has a current active infectious disease or positive serology for human
immunodeficiency virus (HIV), hepatitis C virus (HCV), or hepatitis B virus (HBV).

- Patient has a history of or current auto-immune disease.

- Patient has been vaccinated with live attenuated vaccines within 4 weeks before study
vaccination.