A Study of DSP-0509 in Patients With Advanced Solid Tumors to Determine the Safety and the Pharmacokinetic Profile

The study consists of two stages: an initial dose escalation phase (3-6 patients in each
cohort) based on the Bayesian Logistic Regression Model (BLRM) method with the Escalation
With Overdose Control (EWOC) principle to determine maximum tolerated dose followed by a dose
expansion phase in up to 14 additional subjects. Study participants will initially receive
DSP-0509 intravenously once a week in induction phase, and once every two weeks in a
maintenance phase. If clinical benefit is seen, treatment can continue until disease
progression.

Inclusion criteria

Patients

1. Must have a histologically or cytologically confirmed advanced solid tumor that is
metastatic, unresectable, or recurrent and is refractory to available therapy, or
patient has a contraindication to, is intolerant of, or has declined available
therapy.

2. Must be ≥ 18 years of age

3. Should have all side effects of any prior therapy or procedures for any medical
condition recovered to NCI CTCAE Grade ≤ 1.

4. Must have at least 1 measurable lesion by computed tomography or magnetic resonance
imaging per RECIST version 1.1.

5. Must have a life expectancy ≥ 3 months.

6. Female patients of childbearing age and women < 12 months since the onset of
menopause, except those who have been surgically sterilized or whose sole sexual
partner has been surgically sterilized, must agree to use acceptable contraceptive
methods for the duration of the study and 9 months after the last injection of
DSP-0509. If employing contraception, 2 of the following precautions must be used:
birth control pill, vasectomy of partner, tubal ligation, vaginal diaphragm,
intrauterine system (IUS) or device (IUD), condom and vaginal spermicide, or total
abstinence. Male patients must be surgically sterile or must agree to use a condom and
acceptable contraceptive method with their female partners. Female patients who are
post-menopausal are defined as those with an absence of menses for > 12 consecutive
months.

7. Females of childbearing potential must have a negative serum or urine pregnancy test.

8. Must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.

9. Must have adequate coagulation function at Screening as determined by:

- Prothrombin (PT) international normalized ratio (INR) < 1.5.

- Partial thromboplastin time (PTT) < 1.5 times the upper limit of normal (ULN).

10. Must have adequate hematologic function at Screening as determined by:

- White blood count (WBC) ≥ 3,000/microliter.

- Absolute neutrophil count (ANC) ≥ 1,500/microliter (patient may not use G-CSF or
granulocyte-macrophage colony stimulating factor (GM-CSF) to achieve these WBC
and ANC levels).

- Platelet count ≥ 100 × 103/microliter.

- Hemoglobin (Hgb) ≥ 9.0 g/dL (may not transfuse or use erythropoietin to obtain
this Hgb level).

11. Must have adequate renal and hepatic function at Screening as determined by:

- Serum creatinine < 2.0 mg/dL or < 1.5 times the ULN, whichever is lower.

- Total bilirubin ≤ 1.5 mg/dL (or ≤ 2.0 mg/dL for patients with known Gilbert's
syndrome).

- Aspartate aminotransferase (AST) ≤ 2.5 x ULN.

- Alanine aminotransferase (ALT) ≤ 2.5 x ULN.

12. Must be able to attend study visits as required by the protocol.

Exclusion criteria

1. Has received prior therapy with a TLR agonist.

2. Has received anti-cancer chemotherapy (including molecular-targeted drugs),
radiotherapy, immunotherapy (e.g., vaccines or cytokines), or investigational agents
within the 28 days prior to the first dose of DSP-0509.

3. Receives concurrent systemic (oral or IV) steroid therapy > 10 mg prednisone daily or
its equivalent for an underlying condition.

4. Has had major surgery within the 4 weeks before the first dose of DSP-0509.

5. Has CNS metastases (spinal metastases are acceptable); CNS primary tumors (e.g.,
glioblastoma [GBM]).

6. Has history of seizures other than isolated febrile seizure in childhood; has a
history of a cerebrovascular accident or transient ischemic attack less than 6 months
ago.

7. Has effusions (pleural, pericardial, or ascites) requiring drainage.

8. Has a motor neuron disease, e.g., Parkinson's disorder, multiple sclerosis.

9. Has retinal detachment, ulcerative keratitis, uveitis, Vogt-Koyanagi-Harada syndrome,
choroidal neovascularization, retinopathy/retinitis, thyroid-associated orbitopathy,
idiopathic orbital inflammation, diabetic retinopathy, ischemic retinopathy including
glaucoma-associated retinopathy, retinal vein thrombosis, or a non-healing ocular or
ophthalmic disease (the presence of these conditions would prevent an accurate
assessment of the potential ocular and ophthalmic toxicities of DSP-0509).

10. Has a fever ≥ 38°C within 3 days before signing the ICF.

11. Has interstitial lung disease or active, non-infectious pneumonitis.

12. Has a history of autoimmune disease active or past including but not limited to
inflammatory bowel disease, systemic lupus erythematosus (SLE), ankylosing
spondylitis, scleroderma, or multiple sclerosis. Has any active immunologic disorder
requiring immunosuppression with steroids or other immunosuppressive agents (e.g.,
azathioprine, cyclosporine A) with the exception of patients with isolated vitiligo,
resolved childhood asthma or atopic dermatitis, controlled hypoadrenalism or
hypopituitarism, and euthyroid patients with a history of Grave's disease. Patients
with controlled hyperthyroidism must be negative for thyroglobulin, thyroid peroxidase
antibodies, and thyroid-stimulating immunoglobulin prior to study drug administration.

13. Has a known hypersensitivity to a component of the protocol therapy, DSP-0509, or
another pyrimidine compound.

14. Has a history of another primary cancer within the 5 years prior to enrollment except
for the following: non-melanoma skin cancer, cervical carcinoma in situ, superficial
bladder cancer, or other non-metastatic carcinoma that has been in complete remission
without treatment for more than 5 years.

15. Has abnormal electrocardiograms (ECGs) that are clinically significant, such as QT
prolongation (corrected QT interval [QTc] > 470 msec).

16. In the opinion of the treating Investigator, has any concurrent conditions that could
pose an undue medical hazard or interfere with the interpretation of the study
results; these conditions include, but are not limited to ongoing or active infection,
clinically significant non-healing or healing wounds, concurrent congestive heart
failure (New York Heart Association Functional Classification Class II, III or IV),
concurrent unstable angina, concurrent cardiac arrhythmia requiring treatment
(excluding asymptomatic atrial fibrillation), recent (within the prior 12 months)
myocardial infarction, acute coronary syndrome or stroke within the previous 12
months, significant pulmonary disease (shortness of breath at rest or on mild
exertion) for example due concurrent severe obstructive pulmonary disease, concurrent
hypertension requiring more than 2 medications for adequate control, or diabetes
mellitus with more than 2 episodes of ketoacidosis in the prior 12 months

17. Has an ejection fraction (EF) of 50% or less based on a multigated acquisition (MUGA)
scan or echocardiogram (ECHO).

18. Has the presence of a known active acute or chronic infection including human
immunodeficiency virus (HIV) as determined by enzyme-linked immunosorbent assay
(ELISA) and confirmed by Western blot; and hepatitis B virus (HBV) and hepatitis C
virus (HCV) as determined by hepatitis B surface antigen (HBAg) and hepatitis C
serology.

19. Has a cognitive, psychological or psychosocial impediment that would impair the
ability of the patient to receive therapy according to the protocol or adversely
affect the ability of the patient to comply with the informed consent process,
protocol, or protocol-required visits and procedures.

20. Receives concurrent strong inhibitors or inducers of major cytochrome P450 enzymes
(CYPs).

21. Receives concurrent inhibitors of organic anion transporting peptide (OAT) P1B1 and
OATP1B3.

22. Is pregnant or breastfeeding.