A Phase I, First-Time-in-Human Study of MEDI9197, a TLR 7/8 Agonist, Administered Intratumorally as a Single Agent in Subjects With Solid Tumors or CTCL and in Combination With Durvalumab and/or Palliative Radiation in Subjects With Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 53
- 试验地点
- 1
- 主要终点
- Safety & tolerability as determined by dose limiting toxicities and maximum tolerated or assessed dose of MEDI9197 administered by IT injection in combo with durvalumab and durvalumab plus palliative radiation to subjects with solid tumor cancers.
研究概览
简要总结
To evaluate MEDI9197 when administered by intratumoral injection to subjects with solid tumors and in combination with durvalumab in subjects with solid tumors.
详细描述
This is a multicenter, open-label study to evaluate the TLR 7/8 agonist MEDI9197 delivered by IT injection to subjects with solid tumors and in combination with durvalumab in subjects with solid tumors. The study has a dose escalation design using mTPI-2 to evaluate a range of doses.
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 99 Years（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
- •Any of the following would exclude the subject from participation in the study:
- •Subjects who have received prior immunotherapy [(including but not limited to CTLA-4, oncolytic virus, oncolytic peptide-all require 100 day washout), programmed death ligand (PDL)-1, or programmed cell death 1 antagonists-both require 14 day washout)] are NOT permitted to enroll, with protocol exceptions.
- •Pregnant or lactating.
- •Active bacterial, fungal, or viral infections, including chronic or active hepatitis B, chronic or active hepatitis C, or active hepatitis A. Prior documented infections must have resolved.
- •Active or prior documented autoimmune or inflammatory disorders, with exceptions per protocol. Includes known allergy to sesame oil and/or nuts.
- •Immune-deficiency states - myelodysplastic disorders, marrow failures, human immunodeficiency virus (HIV) infection, history of solid organ transplant or bone marrow allograft, or recent pregnancy.
- •Requires continuous (daily) anticoagulation or antiplatelet therapy (including anti aggregants), acetylsalicylic acid (ASA) or nonsteroidal anti-inflammatory drugs (NSAIDs).
- •History of coagulopathy resulting in uncontrolled bleeding or other bleeding disorders.
- •Rapidly progressing disease per protocol.
- •Untreated or uncontrolled central nervous system (CNS) involvement.
- •Any concurrent chemotherapy, immunotherapy, or biologic or hormonal therapy for cancer treatment; with exceptions per protocol.
- •Unresolved toxicities from prior anticancer therapy, defined as having not resolved to NCI CTCAE v4.03 Grade 0 or 1, with exception of alopecia, vitiligo.
- •Uncontrolled concurrent illness.
- •Cardiac exclusions: New York Heart Association Class 3 or 4 congestive heart failure, uncontrolled hypertension, acute coronary syndrome within 6 months, clinical important cardiac arrhythmia, mean QTC interval corrected for heart rate >500ms.
- •Major surgery within 4 weeks prior to study entry or still recovering from prior surgery.
- •Receipt of live, attenuated vaccine within 28 days prior to study entry.
- •Receipt of any systemic anticancer therapy not mentioned above within the last 2 weeks or 5 half-lives.
- •Cognitive disorder such that informed consent cannot be obtained directly from the subject
- •Subjects who have previously participated in this study and received MEDI9197, or concurrent enrollment in another clinical study involving an investigational treatment.
- •Subjects who have received prior TLR agonists, both systemic and topical.
- •Patients who have received prior therapeutic radiation within 28 days of dosing. All toxicities from prior radiotherapy must have resolved to ≤ Grade 1 or baseline prior to dosing.
- •Body weight < 35 kg
- •Subjects enrolling in Part 3 (ie, receiving durvalumab) must not have a history of interstitial lung disease or pneumonitis.
研究组 & 干预措施
Escalation MEDI9197
MEDI9197
干预措施: MEDI9197 (Drug)
Escalation MEDI9197 with durvalumab
MEDI9197 in combination with durvalumab
干预措施: MEDI9197 (Drug)
Escalation MEDI9197 with durvalumab
MEDI9197 in combination with durvalumab
干预措施: durvalumab (Biological)
Escalation MEDI9197 durvalumab radiation
MEDI9197 in combination with durvalumab and palliative radiation
干预措施: MEDI9197 (Drug)
Escalation MEDI9197 durvalumab radiation
MEDI9197 in combination with durvalumab and palliative radiation
干预措施: durvalumab (Biological)
MEDI9197 with palliative radiation
MEDI9197 in combination with palliative radiation
干预措施: MEDI9197 (Drug)
结局指标
主要结局
Safety & tolerability as determined by dose limiting toxicities and maximum tolerated or assessed dose of MEDI9197 administered by IT injection in combo with durvalumab and durvalumab plus palliative radiation to subjects with solid tumor cancers.
时间窗: From time of informed consent through 90 days after last dose of investigational product
The primary endpoint will be the number (%) of subjects with dose-limiting toxicities, adverse and serious adverse events and other safety parameters.
Safety and tolerability as determined by assessment of dose limiting toxicities and the maximum tolerated dose or maximal assessed dose per protocol of MEDI9197 when administered by intratumoral injection to subjects with solid tumor cancers
时间窗: From time of informed consent through 4 weeks after last dose of investigational product
The primary endpoint will be the number (%) of subjects with dose-limiting toxicities, adverse and serious adverse events and other safety parameters.
Safety and tolerability as determined by assessment of dose limiting toxicities and the maximum tolerated dose or maximal assessed dose per protocol of MEDI9197 when administered by intratumoral injection to subjects with CTCL
时间窗: From time of informed consent through 6 months after last dose of investigational product
The primary endpoint will be the number (%) of subjects with dose-limiting toxicities, adverse and serious adverse events and other safety parameters.
次要结局
- The maximum concentration of MEDI9197 after the first injection(Pre-dose to 24 hours post first dose)
- Percent change from baseline in cluster of differentiation 8 tumor infiltrating lymphocytes in tumor tissue(Baseline to Day 50)
- Percent change from baseline in serum inflammatory cytokine levels(Pre-dose to end of study, up to 24 months)
- Objective response rate(Pre-dose to end of study, up to 24 months)
- Percent change from baseline in Subject Global Assessment (SGA) for subjects with CTCL(Pre-dose to disease progression, up to 12 months)
- The apparent terminal half-life of MEDI9197(Pre-dose to 24 hours post first dose)
- Percent change from baseline in tumor measurements(Pre-dose to disease progression, up to 12 months)
- Percent change from baseline in mSWAT scored for subjects with CTCL(Pre-dose to disease progression, up to 12 months)
- Percent change from baseline in Investigator Global Assessment (IGA) for subjects with CTCL(Pre-dose to disease progression, up to 12 months)
- Percent change from baseline in CAILDS for subjects with CTCL(Pre-dose to disease progression, up to 12 months)
- Duration of response(Pre-dose to end of study, up to 24 months)