A Phase II Randomized, Open Label Study of Ad-RTS-hIL-12 Monotherapy or Combination With Palifosfamide in Subjects With Recurrent/Metastatic Breast Cancer and Accessible Lesions
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 12
- 试验地点
- 8
- 主要终点
- Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
研究概览
简要总结
Phase II, randomized, safety and efficacy study in recurrent/metastatic breast cancer with accessible lesions.
Primary End point is rate of Progression Free Survival (PFS) at the 16 week treatment time point. Hypothesis: Adenoviral vector (Ad-RTS-hIL-12) alone and in combination with chemotherapy (palifosfamide) is safe and efficacious.
详细描述
Multicenter, open-label, randomized study evaluating the safety and efficacy of INXN-1001 (veledimex) and INXN-2001 (Ad-RTS-hIL-12) alone and in combination with palifosfamide.
Part 1 is the safety run-in where a safety assessment will be made after 1 cycle of therapy.
Part 2, eligible subjects will be randomly assigned to active treatment Arms A or C.
Once the monotherapy (Arm A) is determined to be safe and tolerable, Part 1 combination therapy (Arm C) will begin.
Subjects should receive six cycles of study treatment, in the absence of meeting withdrawal criteria.
研究设计
- 研究类型
- Interventional
- 分配方式
- 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
- •Subjects with human epidermal growth factor receptor 2 (HER2)/neu-positive (immunohistochemistry [IHC]) 3+ or fluorescence in situ hybridization-amplified) breast tumors who are eligible for, but who have not received HER2-targeted therapy (eg, trastuzumab)
- •Concomitant anticancer therapies
- •Prior therapies discontinuation periods:
- •Radiation within 3 weeks of enrollment
- •Chemotherapy within 4 weeks of enrollment
- •Nitrosoureas within 6 weeks of enrollment
- •Biologic therapy and/or immunomodulatory therapy, checkpoint inhibitors within 6 weeks of enrollment
- •No washout period is required for endocrine therapy
- •Radiation therapy encompassing >25% of bone marrow
- •History of bone marrow or stem cell transplantation
- •Any congenital or acquired condition leading to inability to generate an immune response
- •Immunosuppressive therapy:
- •Systemic immunosuppressive drugs including corticosteroids (prednisone equivalent >10 mg/day)
- •Immune suppression/requiring immunosuppressive drugs, including organ allografts
- •Active autoimmune disease requiring the equivalent of >10 mg/day of prednisone
- •Major surgery within 4 weeks of study treatment
- •History of prior malignancy, unless the prior malignancy was diagnosed and definitively treated ≥5 years previously with no subsequent evidence of recurrence
- •Subjects with brain or subdural metastases, unless local therapy has completed and corticosteroids have been discontinued for this indication for ≥4 weeks before starting study treatment.
- •Any medications that induce, inhibit, or are substrates of cytochrome P450 (CYP450) 3A4 within 7 days prior to the first dose of study drug
- •Subjects with meningeal carcinomatosis
- •Known significant hypersensitivity to study drugs or excipients
- •History of malabsorption syndrome or other condition that would interfere with enteral absorption
- •International Normalized Ratio (INR) and activated partial thromboplastin time [PTT] <1.5 x ULN, if not therapeutically anticoagulated.
- •New York Heart Association (NYHA) Class II or greater congestive heart failure OR active ventricular arrhythmia requiring medication
- •Any other unstable or clinically significant concurrent medical condition
- •Localized infection at site of injectable lesion(s) requiring antiinfective therapy within 2 weeks of the first dose of study drug.
研究组 & 干预措施
Ad-RTS-hIL-12 and veledimex
Experimental study drug monotherapy arm (A)
干预措施: Ad-RTS-hIL-12 and Veledimex (Genetic)
Ad-RTS-hIL-12 and Palifosfamide
Study drug combination therapy arm (C)
干预措施: Ad-RTS-hIL-12 and Veledimex (Genetic)
Ad-RTS-hIL-12 and Palifosfamide
Study drug combination therapy arm (C)
干预措施: Palifosfamide (Drug)
结局指标
主要结局
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
时间窗: 16 months
This measure will capture the incidence of Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and AEs leading to discontinuation. As per the protocol, safety and tolerability were assessed by monitoring adverse events, physical examinations, vital signs, electrocardiograms (ECGs), and clinical laboratory evaluations.
16-Week Progression-Free Survival (PFS) Rate
时间窗: 16 weeks
This is the primary efficacy endpoint, defined as the proportion of subjects who had not progressed or died prior to 16 weeks from the date of their first dose. Progression was determined by modified Response Evaluation Criteria in Solid Tumors
次要结局
- Best Overall Response (BOR) by mRECIST v1.1(24 weeks)
- Estimate PFS by Modified RECIST v1.1(16 months)
- Area Under the Plasma Concentration-Time Curve From 0 to 24 Hours (AUC0-24) of INXN-1001(Cycle 1 Day 1 and Cycle 1 Day 7)
- Change From Baseline in MUC-1 Specific T-Cell Response by ELISPOT Assay(Screening and the Post-Treatment Safety Assessment visit (28 days after the last dose of study drug), with the final assessment occurring up to 7 months after the start of treatment.)
- Change From Baseline in Serum Interferon-gamma (IFN-γ) Levels(Screening, 24 hours after the first injection (Day 2), and at the Post-Treatment Safety Assessment visit, with the final assessment occurring up to 7 months after the start of treatment.)
- Change From Baseline in Serum Interleukin-12 (IL-12) Levels(Screening, 24 hours after the first injection (Day 2), and at the Post-Treatment Safety Assessment visit, with the final assessment occurring up to 7 months after the start of treatment.)
- Change From Baseline in CD3+ CD4+ T-Cell Count(Screening, Cycle 1 the Post-Treatment Safety Assessment visit Day 28 ± 3, and Follow-Up Tumor Assessment visits Day 63 ± 7)
- Change From Baseline in CD3+ CD8+ T-Cell Count(Screening, Cycle 1 the Post-Treatment Safety Assessment visit Day 28 ± 3, and Follow-Up Tumor Assessment visits Day 63 ± 7)
- Maximum Plasma Concentration (Cmax) of INXN-1001(Cycle 1 Day 1 and Cycle 1 Day 7. On Day 1, samples were collected pre-dose and at 0.5, 1, 2, 4, and 6 hours post-dose. On Day 7, samples were collected pre-dose and at 1-2 and 4-6 hours post-dose)
- Time to Maximum Plasma Concentration (Tmax) of INXN-1001(Cycle 1 Day 1 and Cycle 1 Day 7)
- Clinical Benefit Rate (CBR)(From the first dose of study treatment for up to 1 year.)