This is a multi-center, Phase ½ clinical study for patients with advanced solid tumors. The
study consists of 2 treatment arms - a monotherapy arm and a combination arm. The monotherapy
arm has 3 parts: Dose Escalation (Part A), Dose Expansion (Part B) and Maintenance Dose
Schedule Evaluation (Part C). The combination arm has Dose Escalation (Part A) only.
The study consists of two treatment arms- a monotherapy arm and a combination arm. The
monotherapy arm has 3 parts: the Dose Escalation part (Part A) will evaluates 5 provisional
dose levels/cohorts (3-6 patients in each cohort) and will enroll approximately 21-30
patients with solid tumors based on the Bayesian Logistic Regression Model (BLRM) method with
the Escalation with Overdose Control (EWOC) principle to determine the maximum tolerated dose
(MTD). DSP-0509 will be administered as a single agent q1w for 4 weeks beginning on Day 1
during induction treatment followed by q2w administration until discontinuation during
maintenance treatment. Within each cohort, patients will be entered in a staggered fashion as
an additional safety measure. That is, treatment of a new patient will be delayed at least 48
hours after the first dose of the most recent patient entered within each cohort.
Next is the Dose Expansion part (Part B) in which approximately 20-40 total patients with a
diagnosis of either melanoma or head and neck squamous cell carcinoma (HNSCC) will be broken
out into each of the following 4 sub-groups (5 to 10 patients per group): Melanoma CD8+ high,
melanoma CD8+ low, HNSCC CD8+ high and HNSCC CD8+ low. These patients will be treated using
the RP2D of DSP-0509 which is given to them 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.
The 3rd part of monotherapy is the Maintenance Dose Schedule Evaluation (Part C) which will
enroll approximately 3-6 patients with solid tumors to assess the safety and tolerability of
DSP-0509 using the RP2D that will be administered IV once a week (q1w) during the induction
treatment followed by every 3 weeks (q3w) during maintenance treatment to these patients.
The second treatment arm, combination arm, has just 1 part. The Dose Escalation part (Part A)
will start once safety and tolerability has been confirmed for the 2nd dose escalation cohort
in monotherapy Part A. The starting dose level of DSP-0509 will be at least 1 dose level
below that of the second dose level tolerated in monotherapy Part A. Approximately 21-30
patients with solid tumors will be enrolled into Part A of the combination arm. DSP-0509 will
be administered using the same dosing schedule as monotherapy arm Part A. Pembrolizumab will
be administered using a dose and schedule as described in the approved label (200 mg IV q3w).
Within each cohort, patients will be entered in a staggered fashion (48 hrs. between the dose
another patient) as an additional safety measure.
Patients must fulfill each of the following requirements:
For enrollment in monotherapy arm only:
1. Must have a histologically or cytologically confirmed
1. Part A & C advanced solid tumor that is metastatic or unresectable and recurrent
and/or refractory to available therapy.
2. Part B - metastatic or unresectable and recurrent
- Melanoma with acquired resistance to ICIs (defined as previous treatment
with ICIs [PD 1 or PD-L1 inhibitors] accompanied by objective clinical
benefit [SD for at least 24 weeks, PR, or CR as the best clinical response
to ICIs], followed by systemic progression of disease during or within 3
months after the last dose of ICI treatment according to Investigator
- HNSCC with 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 or urine 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:
1. Prothrombin international normalized ratio < 1.5.
2. Partial thromboplastin time < 1.5 times the upper limit of normal (ULN).
10. Must have adequate hematologic function at Screening as determined by:
1. White blood cell (WBC) count ≥ 3,000/microliter.
2. 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).
3. Platelet count ≥ 100 × 103/microliter.
4. 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
4. Alanine aminotransferase ≤ 2.5 times ULN (≤ 5 times ULN for patients with liver
12. Must be able to attend study visits as required by the protocol.
13. For monotherapy arm Parts A and C, and combination arm Part A, before administration
of the first DSP-0509 infusion, the patient must be able to provide archival tissue
with enough nontarget tumor tissue to provide the required number of slides needed for
baseline assessments, or patient must consent to undergo tumor biopsy to acquire
sufficient tumor tissue. (Sites need to refer to the current version of the "Tumor
Collection & Shipment Instructions Manual" to determine how many slides are required
for each patient. The tissue manual breaks these numbers out based off patient's study
Arm/Part enrolled to as well as if patient consented to optional future testing).
14. For monotherapy arm Part B, before administration of the first DSP 0509 infusion, the
patient must consent to undergo tumor biopsy to acquire sufficient tissue at each of
the pretreatment and posttreatment evaluations.
15. For combination arm Part A, the patient must be ICI naïve and have a histologically or
cytologically confirmed advanced solid tumor that is metastatic or unresectable and
recurrent and/or refractory to available therapy and is a condition for which
pembrolizumab is the standard of care treatment. Eligible tumor types for treatment
with pembrolizumab for combination arm include:
- Non-small-cell lung cancer
- Urothelial carcinoma
- Microsatellite instability-high cancer
- Gastric cancer
- Cervical cancer
- Hepatocellular carcinoma
- Merkel cell carcinoma
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 4 weeks before the first dose of DSP-0509. Local palliative radiotherapy is
permitted; however, if the radiotherapy is to a target lesion, that lesion must be
excluded from tumor response assessments.
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 central nervous system (CNS) metastases (including 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
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
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 autoimmune disease active or past including but not limited to
inflammatory bowel disease, systemic lupus erythematosus, ankylosing spondylitis,
scleroderma, or multiple sclerosis. Has any active 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
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
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
22. Is pregnant or breastfeeding.
For enrollment in combination arm only:
Has a known hypersensitivity to pembrolizumab or its components.