An Exploratory First in Human Phase I Clinical and Pharmacokinetic Study of Intra-tumoral Administration of BO-112 in Adult Patients With Aggressive Solid Tumors, With an Extension Cohort in Combination With Anti-PD1 Treatment
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 44
- 试验地点
- 7
- 主要终点
- Number of subjects with adverse events
研究概览
简要总结
Part 1: 16 to 32 patients with aggressive solid tumors from whom biopsies can be obtained, will receive BO-112 through IT administration.
Injected lesions must be palpable and biopsiable at the time of injection, and biopsied after 7-14 days. Patients will not receive an alternative therapy during the period comprising from first and second biopsy. BO-112 will be administered at a starting dose. Upon confirmation of the safety profile of the starting dose and evaluation of the pharmacokinetic (PK) profile, three additional dose levels are expected to be tested.
During the course of the study, subjects will be examined for any side effects that may occur (safety and tolerability).
Additionally this study will also study BO-112 biological activity, the innate and adaptive immune system response and signaling pathways, as well as signs of clinical relevance, will be studied.
Part 2: An additional 30 patients with progressive disease while on anti-PD1 treatment for an approved indication, will receive BO-112 through IT administration in combination with the anti-PD1 treatment to evaluate the safety and tolerability of the combination.
Injected lesions must be palpable and biopsiable at the time of injection. Patients will continue with their anti-PD1 treatment. During the course of the study, patients will be examined for any side effects that may occur (safety and tolerability).
Additionally this part of the trial will also study BO-112 biological activity, the innate and adaptive immune system response and signaling pathways, as well as signs of clinical response
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Other
- 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
- •Patients age 18 years or more on the day of signing informed consent form.
- •Histologically or cytologically confirmed aggressive solid tumors
- •Patients must have:
- •Biopsy-accessible tumors
- •No prior anticancer treatment during the last 14 days
- •Additional inclusion criteria for Part 2: disease progression on treatment with anti-PD1 antibody for an approved indication
排除标准
- •Other relevant and clinically significant concomitant diseases or adverse clinical conditions which may jeopardize patient safety:
- •Increased cardiac risk: congestive heart failure; or unstable angina pectoris; or arrhythmia requiring treatment or uncontrolled arterial hypertension; or myocardial infarction within 12 months before inclusion in the study.
- •Patients with active central nervous system (CNS) lesions (including carcinomatous meningitis) will be excluded. However, patients will be eligible if:
- •All known CNS lesions have been treated with stereotactic therapy or surgery, AND
- •There has been no evidence of clinical and radiographic disease progression in the CNS for ≥ 4 weeks after radiotherapy or surgery, and has not required to increase in the last 4 weeks their steroids use or has not started a new course of steroids
- •Whole brain radiotherapy is not allowed, with the exception of patients who have had definitive resection or stereotactic therapy of all radiologically detectable parenchymal brain lesions.
- •Active infection.
- •Significant non-neoplastic liver disease (e.g., cirrhosis, active chronic hepatitis B or C).
- •Any clinically significant abnormality on history or examination including diagnosis of immunodeficiency or receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study medication (physiologic doses of corticosteroids may be approved after consultation with the Sponsor).
- •Additional exclusion criteria for Part 2: Grade 3-4 toxicity due to anti-PD1 antibody or permanent discontinuation of anti-PD1 antibody due to immune related or other adverse reaction.
研究组 & 干预措施
Part 1: BO-112 IT
BO-112 dose 1 (starting dose) intratumoral injection. BO-112 dose 2, 3 and 4 are expected to be tested, upon confirmation of the safety profile of the starting dose.
干预措施: Part 1: BO-112 (Drug)
Part 2: BO-112 IT
Combination treatment of BO-112 intratumoral injections with standard of care nivolumab intravenous treatment
Or Combination treatment of BO-112 intratumoral injections with standard of care pembrolizumab intravenous treatment
干预措施: Part 2: BO-112 (Drug)
结局指标
主要结局
Number of subjects with adverse events
时间窗: Part 1: Day 30 after administration of the last dose. Part 2: 12 weeks and for patients who continue up to 1 year
To evaluate the safety and tolerability of B0-112 in terms of adverse events at every visit
次要结局
- Anti-tumor activity(12 weeks and for patients who continue up to 1 year)
- Plasma levels of BO-112(Part 1: 0-15-30-240 minutes and 24 hours after administration of the drug. Part 2: 1 day)
- Circulating cytokines including type I IFNs, TNFalpha and IL6 (by ELISA)(Part 1: At three independent points during the study. Day 7-1 prior to administration, 24 hours after administration and 7-14 days after administration of the agent. Part 2: 12 weeks)