A Phase I Clinical Study of DSP-7888 Dosing Emulsion in Adult Patients With Advanced Malignancies
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 24
- 试验地点
- 8
- 主要终点
- Determination of the safety and tolerability of DSP-7888 Dosing Emulsion by assessing dose-limiting toxicities (DLTs)
研究概览
简要总结
This is a multicenter, open label, Phase 1 dose-escalation study of DSP-7888 Dosing Emulsion administered to adult patients with advanced malignancies. Patients will be administered escalating doses of DSP-7888 Dosing Emulsion intradermally or subcutaneously in accordance with the following regimen: once weekly for four weeks during the Induction Phase, once every 7 to 14 days for 6 weeks during the Consolidation Phase, and once every 14 to 28 days until a discontinuation criterion is met during the Maintenance Phase. Once RP2D is determined from either the intradermal or subcutaneous group, an additional 40 patients evaluable for response may be enrolled as an expansion cohort at this dose and route of administration to confirm safety and tolerability. Separate from the dose-ascending cohort and RP2D expansion cohort described previously, and once the intradermal dose-ascending cohort is completed, up to 20 MDS patients who are refractory to treatment with hypomethylating agents (HMAs) will be enrolled into an MDS expansion cohort. Of these 20 MDS patients, one-half will receive DSP-7888 at 10.5 mg according to the modified schedule employed in Phase 1 (every week for 4 weeks, every 2 weeks until Week 24, and then every 4 weeks; [MDS Cohort 1]). The other half of the MDS patients will receive DSP-7888 at 10.5 mg in an alternative dosing schedule where DSP-7888 is administered every 2 weeks until Week 24, after which it will be administered every 4 weeks (MDS Cohort 2).
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- •Patient has an extensively disseminated primary glioblastoma
- •Patient has acute promyelocytic leukemia (APML)
- •For AML and MDS patients: patients with a dry tap on bone marrow aspiration during screening
- •Patient has symptomatic brain metastases (i.e., metastases that are accompanied by neurological symptoms or that require treatment with corticosteroids)
- •Patient has an infection requiring treatment with systemic antibiotics or antiviral medication or has completed treatment for such an infection within 14 days prior to planned first dose of study drug
- •Patient requires systemic, pharmacologic doses of corticosteroids (equivalent to >30 mg hydrocortisone/day) Note: Replacement doses (equivalent to ≤ 5 mg prednisone/day), and topical, ophthalmic, and inhalation steroids are permitted as needed
- •Patient has a positive test for Hepatitis B surface antigen, Hepatitis C antibody, human immunodeficiency virus HIV-1 or HIV-2 antibody, or has a history of a positive result for hepatitis C virus (HCV) or HIV
- •Patient has received any of the following treatments within the specified timeframes: a. Surgery, radiotherapy, chemotherapy (including molecular-targeted drugs): 4 weeks (28 days), b. Immunosuppressants or cytokine formulations (excluding G-CSF): 4 weeks (28 days), c. Endocrine therapy or immunotherapy (including biological response modifier therapy): 2 weeks (14 days)
- •Patient has an unresolved ≥ Grade 2 adverse event (AE) from a previous antineoplastic treatment, excluding alopecia and phlebitis
- •Patient has had surgery within 4 weeks prior to first dose
- •Woman who is pregnant or lactating or has a positive pregnancy test at screening. If a woman has a positive pregnancy test, further evaluation may be conducted to rule out ongoing pregnancy to allow the patient to be eligible
- •Patient has any concurrent autoimmune disease or has a history of chronic or recurrent autoimmune disease; these include but are not limited to: multiple sclerosis, Grave's disease, vasculitis, systemic lupus erythematosus, rheumatoid arthritis, systemic sclerosis, myasthenia gravis, ankylosing spondylitis, Wegener's granulomatosis, ulcerative colitis, Crohn's disease, psoriasis requiring systemic therapy, pemphigus, temporal arteritis, dermatomyositis, Sjögren's syndrome, Goodpasture's syndrome, interstitial pneumonitis, interstitial nephritis, or Henoch-Schönlein purpura
- •Patient has, in the opinion of the treating investigator, any intercurrent conditions that could pose an undue medical hazard or interfere with the interpretation of the study results; these conditions include, but not limited to: congestive heart failure (New York Heart Association (NYHA) Class III or IV), unstable angina, cardiac arrhythmia requiring treatment, recent (within the prior 6 months) myocardial infarction, acute coronary syndrome or stroke, severe obstructive pulmonary disease, hypertension requiring more than 2 medications for adequate control, or diabetes mellitus with more than 2 episodes of ketoacidosis in the prior 12 months
- •Patient has Common Toxicity Criteria for Adverse Effects (CTCAE) v 4.0 grade ≥ 2 hemorrhage
- •Patient has pleural effusion, ascites, or pericardial fluid requiring drainage Note: Patient who had drain removal ≥ 14 days prior to planned first dose of study drug and has no sign of worsening is eligible
- •Patient has any other medical, psychiatric, or social condition, including substance abuse, that in the opinion of the investigator would preclude compliance with the requirements of this study
- •Patients with two or more active malignancies (synchronous multiple cancers, or metachronous multiple cancers with a disease-free period of ≤ 5 years, with the exception of carcinoma in situ, mucosal carcinoma, or other carcinomas that have been curatively treated with local therapy)
- •Patient has had previous treatment with the study drug or other Wilms' tumor 1 (WT1)-related immune therapy
- •Patient has history of allergy to any oily drug products
- •Patient has a known hypersensitivity to any of the components of the study drug
研究组 & 干预措施
Dosing Escalation Cohort
Patients will be administered escalating doses of DSP-7888 Dosing Emulsion intradermally or subcutaneously. Dose-escalation will proceed according to the Criteria for Dose Escalation and Criteria for Determination of Dose-Limiting Toxicity (DLT) as indicated below. Dose Level I: 3.5 mg, Dose Level II: 10.5 mg, Dose Level III: 17.5 mg
干预措施: DSP-7888 Dosing Emulsion (Drug)
MDS Cohort 1
Patients will be intradermally administered of DSP-7888 at 10.5 mg every week for 4 weeks, every 2 weeks until Week 24, and then every 4 weeks.
干预措施: DSP-7888 Dosing Emulsion (Drug)
MDS Cohort 2
Patients will be intradermally administered of DSP-7888 at 10.5 mg every 2 weeks until Week 24, and then every 4 weeks.
干预措施: DSP-7888 Dosing Emulsion (Drug)
结局指标
主要结局
Determination of the safety and tolerability of DSP-7888 Dosing Emulsion by assessing dose-limiting toxicities (DLTs)
时间窗: 4 weeks
Determination of the safety and tolerability of DSP-7888 Dosing Emulsion by assessing duration of study treatment
时间窗: 12 months
Determination of the Recommended Phase 2 Dose (RP2D) by assessing dose-limiting toxicities (DLTs)
时间窗: 4 weeks
次要结局
- Assessment of the preliminary anti-tumor activity by assessing Progression-Free Survival (solid tumors and acute myeloid leukemia (AML))(12 months)
- Overall Survival(12 months)
- Pharmacodynamic activity of DSP-7888 Dosing Emulsion as assessed by biomarker analysis(12 months)