Clinical Trials /

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

NCT03416335

Description:

This is a Phase 1, open label, multi-center study of intravenously administered DSP-0509 in adult subjects with advance solid tumors that are refractory to standard treatment.

Related Conditions:
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: A Study of DSP-0509 in Patients With Advanced Solid Tumors to Determine the Safety and the Pharmacokinetic Profile
  • Official Title: A First-in-Human Phase I Trial to Determine the Safety and the Pharmacokinetic Profile of DSP-0509, a Synthetic Toll-Like Receptor 7 (TLR-7) Agonist, in Adult Patients With Advanced Solid Tumors

Clinical Trial IDs

  • ORG STUDY ID: BBI-DSP0509-101
  • NCT ID: NCT03416335

Conditions

  • Neoplasms

Interventions

DrugSynonymsArms
DSP-0509DSP-0509

Purpose

This is a Phase 1, open label, multi-center study of intravenously administered DSP-0509 in adult subjects with advance solid tumors that are refractory to standard treatment.

Detailed Description

      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.
    

Trial Arms

NameTypeDescriptionInterventions
DSP-0509ExperimentalUp to five dose levels will be investigated in dose-escalating phase to identify a maximum tolerated dose (MTD). Dose levels will be selected in a pharmacokinetic (PK)-guided manner for overdose protection to maximize patient safety. Once the recommended Phase 2 dose (RP2D) has been established, patients will be treated with the RP2D to explore preliminary antitumor activity and safety profile in dose-expansion phase.
  • DSP-0509

Eligibility Criteria

        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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Maximum tolerated dose by assessing dose-limiting toxicities (DLTs)
Time Frame:4 weeks
Safety Issue:
Description:Dose-escalation phase

Secondary Outcome Measures

Measure:Pharmacokinetics for DSP-0509 by assessing plasma concentration
Time Frame:8 weeks
Safety Issue:
Description:
Measure:Objective response rate (ORR) by RECIST
Time Frame:6 months
Safety Issue:
Description:Defined as the proportion of patients with a documented complete response or partial response (CR + PR) based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
Measure:ORR by immune RECIST (iRECIST)
Time Frame:6 months
Safety Issue:
Description:Defined as the proportion of patients with a documented complete response or partial response (CR + PR) based on iRECIST.
Measure:Duration of response (DoR) by RECIST
Time Frame:6 months
Safety Issue:
Description:Defined as the time from first documentation of response until the time of first documentation of disease progression by RECIST v1.1.
Measure:DoR by iRECIST
Time Frame:6 months
Safety Issue:
Description:Defined as the time from first documentation of response until the time of first documentation of disease progression by iRECIST.
Measure:Progression free survival (PFS) by RECIST
Time Frame:12 months
Safety Issue:
Description:Defined as the time from first dose to the earlier date of assessment of progression or death by any cause in the absence of progression by RECIST v1.1.
Measure:PFS by iRECIST
Time Frame:12 months
Safety Issue:
Description:Defined as the time from first dose to the earlier date of assessment of progression or death by any cause in the absence of progression by iRECIST.
Measure:DSP-0509-induced changes in cytokine levels
Time Frame:8 weeks
Safety Issue:
Description:

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Boston Biomedical, Inc

Trial Keywords

  • DSP-0509
  • Toll-Like Receptor 7 (TLR-7)
  • BLRM (Bayesian Logistic Regression Model)

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