Study of IMF-001 in Patients With Malignancies Expressing NY-ESO-1

NY-ESO-1 was isolated by serological analysis of recombinant cDNA expression libraries
(SEREX), using tumor mRNA and autologous serum from an esophageal cancer patient. Reverse
transcription-polymerase chain reaction (RT-PCR) analysis showed that NY-ESO-1 displayed the
typical expression pattern of cancer testis antigens (CT antigens). NY-ESO-1 mRNA was
expressed only in testis of normal tissues tested and in various types of cancer, including
lung cancer, breast cancer, malignant melanoma and bladder cancer. Since testis is an
immune privileged organ where HLA molecules are not expressed, these antigens can be
considered tumor-specific.

IMF-001 is a CHP-NY-ESO-1 complex consisting of recombinant NY-ESO-1 protein and cholesteryl
hydrophobized pullulan (CHP). CHP forms colloidally stable nanoparticles in water and
complexes with substrate such as NY-ESO-1 protein.

It is well known that exogenous antigen proteins can induce specific CD4+ T cells but not
specific CD8+ T cell. Dendritic cells pulsed with IMF-001 induced NY-ESO-1 specific CD8+ T
cells in blood samples of 4 healthy volunteers. These data suggest that immunization of
patients with IMF-001 can evoke not only specific CD4+ T cells responses but also specific
CD8+ T cell response to NY-ESO-1 more effectively than NY-ESO-1 protein alone. Similar
results for both cellular and humoral immunity in response to NY-ESO-1 protein were observed
in previous clinical investigational studies with IMF-001.

Inclusion Criteria:

1. Patients with histologically proven progressive or metastatic solid tumors expressing
NY-ESO-1, who have failed standard treatment and have no other effective treatment
available (solid tumors such as melanoma, breast cancer, ovarian cancer, prostate
cancer, esophageal cancer, uterine cancer, and sarcoma frequently express NY-ESO-1).
Patients with malignant melanoma stages IIb and III, or stage IV melanoma that has
been completely resected, or with stage I and II uterine serous cancer, clear cell
carcinoma, or carcinosarcoma with documented expression of NY-ESO-1 may also enroll
as they have a 50% or greater chance of developing recurrent disease.

2. Documentation of tumor cells expressing NY-ESO-1 antigen as determined by
immunohistochemistry.

3. Must have target lesion(s) measurable or non-measurable by RECIST version 1.1.
Exceptions: Patients with stages IIb or III melanoma, or stage IV melanoma that has
been completely resected, will have no target lesions measurable by RECIST version
1.1 but may enroll; patients with prostate cancer without measurable disease but with
rising prostate specific antigen (PSA) levels may enroll; patients with resected
stage I and II uterine serous cancer, clear cell carcinoma, and carcinosarcoma will
have no target lesions measurable by RECIST but may enroll.

4. Has recovered from all acute adverse effects of prior therapy, with the exception of
alopecia.

5. Laboratory values within the following limits:

- Hemoglobin ≥ 8.0 g/dL

- WBC count ≥ 2.0 x 10^9/L

- ANC ≥ 1.0 x 10^9/L

- Platelet count ≥ 75 x 10^9/L

- Serum creatinine ≤ 1.5 mg/dL

- AST & ALT ≤ 2.5 x ULN (≤ 5 x ULN if with hepatic metastases)

- Serum total bilirubin ≤ 1.5 x ULN

6. Performance status of 0 or 1 (ECOG Scale).

7. Life expectancy ≥ 4 months.

8. Ages 18 years or over.

9. Patients with central nervous system metastases may be included if they are treated
and stable for 2 months without the need for administration of steroids. Patients
with unstable metastatic CNS disease are excluded.

10. A negative pregnancy test must be documented at the screening/baseline visit for
women of childbearing potential. A female patient of childbearing potential, and a
male patient with a female partner of childbearing potential, must be using at least
one form of Investigator-approved contraception while on-study and for at least 1
month after their last administration of study therapy.

11. Able and willing to give written informed consent.

Exclusion Criteria:

1. Clinically significant heart disease (NYHA Class III or IV).

2. Serious active infection requiring antibiotics.

3. Bleeding disorders.

4. Unstable metastatic disease in the central nervous system.

5. Concomitant systemic treatment with corticosteroids. Topical steroids are permitted.

6. History of any severe or life-threatening hypersensitivity or allergic reaction.

7. Known HIV infection.

8. History of immunodeficiency disease or autoimmune disease, including scleroderma,
Sjögren's syndrome, lupus erythematosus, idiopathic thrombocytopenic purpura (ITP),
multiple sclerosis, or rheumatoid arthritis.

9. Has received anticancer chemotherapy, immunotherapy, radiotherapy or any other
investigational agent within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior
to enrollment. Concomitant immunosuppressive therapy is not permitted. Adjuvant
interferon alpha is not allowed for patients with stages IIb, III or IV melanoma.
Prostate cancer patients with PSA only recurrence may have had previous androgen
deprivation therapy, provided the 4 week washout period is observed.

10. Pregnant or lactating women.