| Eligibility |
Inclusion Criteria:
Patients must fulfill each of the following requirements:
1. Must have a histologically or cytologically confirmed advanced solid tumor that meets
the following additional specifications
1. Monotherapy Part A (Dose Escalation) advanced solid tumor that is metastatic or
unresectable and recurrent and /or refractory to available therapy.
2. Combination Part B (Dose Escalation)- advanced solid tumors that are (a) metastatic or
unresectable and recurrent and/or refractory to available therapy; (b) a condition for
which pembrolizumab is an approved treatment: and (c) in patients who either have
shown primary or acquired resistance to immune checkpoint inhibitors (ICIs)
3. Combination Arm C (Dose Expansion), Phase 2 - Advanced HNSCC tumors of the oropharynx,
oral cavity, hypopharynx, larynx, lip, or sinus that are (a) metastatic or
unresectable, and recurrent and/or refractory to available therapy, (b) in patients
who have been treated with pembrolizumab or other PD-1 or PD-L1 inhibitors in
monotherapy, and (c) who have subsequently shown primary or acquired resistance to
ICIs.
For enrollment in both arms:
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 CTCAE = Grade 1 (except alopecia).
4. Must have at least 1 measurable lesion by computed tomography or magnetic resonance
imaging per RECIST v1.1.
5. Must have a life expectancy = 3 to 6 months.
6. Female patients of childbearing age and women < 12 months since the onset of
menopause, except those who have been surgically sterilized (tubal ligation) or whose
sexual partner(s) is surgically sterilized (vasectomy), must agree to use acceptable
contraceptive methods for the duration of the study and for 9 months after the date of
their last DSP-0509 infusion. If employing contraception, 2 of the following
precautions must be used: birth control pill, vaginal diaphragm, intrauterine system
or device, condom or vaginal spermicide. Female patients who are postmenopausal are
defined as those with an absence of menses for = 12 consecutive months. Male patients
must be surgically sterilized (vasectomy) or their female sexual partner(s) must be
surgically sterilized (tubal ligation) to avoid using contraception. If they do not
meet this criterion, then male patients or must agree to use a condom as well as one
of the acceptable contraceptive methods listed above with their female partner(s) who
meets the criteria of either being of childbearing age or is < 12 months since the
onset of menopause. Male patients and their female partner(s) must agree to use
acceptable contraception methods for the duration of time the male patient is on the
study and for 9 months after the date of his last DSP 0509 infusion.
7. Females of childbearing potential must have a negative serum pregnancy test.
8. Must have an Eastern Cooperative Oncology Group performance status of 0 to 1.
9. Must have adequate coagulation function at Screening as determined by:
a. Prothrombin international normalized ratio < 1.5. b. Partial thromboplastin time < 1.5
times the upper limit of normal (ULN).
10. Must have adequate hematologic function at Screening as determined by:
a. White blood cell (WBC) count = 3,000/microliter. b. Absolute neutrophil count (ANC) =
1,500/microliter (patient may not use granulocyte colony stimulating factor or
granulocyte-macrophage colony stimulating factor to achieve these WBC and ANC levels).
c. Platelet count = 100 × 103/microliter. d. 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:
1. Serum creatinine < 2.0 mg/dL or < 1.5 times the ULN, whichever is lower.
2. Total bilirubin = 1.5 mg/dL or < 1.5 times the ULN, whichever is lower (or = 2.0 mg/dL
for patients with known Gilbert syndrome).
3. Aspartate aminotransferase = 2.5 times ULN (= 5 times ULN for patients with liver
metastases).
4. Alanine aminotransferase = 2.5 times ULN (= 5 times ULN for patients with liver
metastases).
12. Must be able to attend study visits as required by the protocol.
13. Prior to the first DSP-0509 infusion, the patient must be able to provide tumor
tissue for baseline studies either as (a) a block of archival tissue sufficient to
provide the required number of slides (b) a sufficient number of fixed, unstained
slides of archival tissue or (c) consent to undergo tumor biopsy to acquire sufficient
tumor tissue. (Sites need to refer to the current version of the "Sample Collection &
Shipment Instructions Manual" to determine how many slides are required for each
patient as these numbers vary based on (a) the study Arm/Part in which the patient is
enrolled and (b) whether the patient consented to optional future testing).
In addition to the above criteria, patients must meet the following criteria to be
eligible to enroll in Combination Arm C:
14. Have at least one accessible tumor for biopsy. This accessible lesion must be
considered as non-measurable per RECIST criteria, v1.1.
15. Be platinum refractory, PD-1 or PD-L1 exposed, and have no more than 3 lines of
prior therapy for advanced/metastatic disease
16. Have a known status of PD-L1 combined positive score (CPS)
17. Have a known HPV status
Exclusion Criteria:
Patients with any of the following will be excluded from the study:
For enrollment in both arms:
1. Has received prior therapy with a TLR agonist, excluding a topical TLR agonist.
2. Has received anticancer chemotherapy (including molecular-targeted drugs),
radiotherapy, immunotherapy (eg, vaccines or cytokines), or investigational
agents within the 3 weeks before the first dose of DSP-0509. Local palliative
radiotherapy is permitted3. Receives concurrent systemic (oral or IV) steroid
therapy > 10 mg prednisone daily or its equivalent for an underlying condition.
4. Not fully recovered from major surgery before the first dose of DSP-0509.
5. Has central nervous system (CNS) metastases (including leptomeningeal metastases,
spinal metastases) or CNS primary tumors, eg, glioblastoma.
6. Has a 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 neurodegenerative disease, eg, motor neuron disease, Parkinson disease,
Alzheimer disease, Huntington disease.
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.
10. Has a fever = 38°C within 3 days before the first dose of study treatment.
11. Has interstitial lung disease or active noninfectious pneumonitis.
12. Has a history of active autoimmune or immunologic disorder requiring
immunosuppression with steroids or other immunosuppressive agents (eg, azathioprine,
cyclosporine A) except for patients with isolated vitiligo, resolved childhood asthma
or atopic dermatitis, controlled hypoadrenalism or hypopituitarism, and euthyroid
patients with a history of Grave disease. Patients with controlled hyperthyroidism
must be negative for thyroglobulin, thyroid peroxidase antibodies, and
thyroid-stimulating immunoglobulin before study drug administration.
13. Has a known hypersensitivity to a component of the protocol therapy, DSP-0509, or
another pyrimidine.
14. Has a history of another primary cancer within the 5 years before enrollment
except for the following: non-melanoma skin cancer, cervical carcinoma in situ,
superficial bladder cancer, or other nonmetastatic carcinoma that has been in complete
remission without treatment for more than 5 years.
15. Has abnormal ECGs that are clinically significant, such as QT prolongation (QTc >
480 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 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 of 50% or less based on a MUGA scan or ECHO.
18. Has the presence of a known active acute or chronic infection including human
immunodeficiency virus as determined by enzyme-linked immunosorbent assay and
confirmed by Western blot; and hepatitis B virus and hepatitis C virus as determined
by hepatitis B surface antigen 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 of cytochrome P450 2C8.
21. Receives concurrent inhibitors of organic anion transporting peptide (OATP)1B1 and
OATP1B3.
22. Is pregnant or breastfeeding.
23. Has active neurological or inflammatory or auto immune disorders (e.g.
Guillain-Barre Syndrome, Amyotrophic Lateral Sclerosis)
The following exclusion applies only to enrollment in Combination arms Part B & C:
24. Has a history of immune-related adverse events (irAEs) resulting in permanent
discontinuation of ICI treatment.
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