A Phase 1b, Open-Label, Single-Arm Dose-Expansion Study of IK-175, an Oral Aryl Hydrocarbon Receptor Inhibitor, in Combination With Nivolumab in Patients With Primary PD-1 Inhibitor Resistant Metastatic or Locally Incurable, Recurrent HNSCC
试验速览
- 阶段
- 1 期
- 状态
- 撤回
- 试验地点
- 4
- 主要终点
- Frequency and severity of treatment related adverse events (TRAEs) in subjects receiving IK-175 in combination with nivolumab [Safety and Tolerability]
研究概览
简要总结
This is a phase 1b study in adult patients diagnosed with resistant or recurrent head and neck squamous cell carcinoma (HNSCC) designed to assess the safety and tolerability of IK-175 in combination with nivolumab. Disease response, pharmacokinetics (PK), pharmacodynamics, and response biomarkers will also be assessed.
详细描述
This is an open-label, multicenter, phase 1b dose-expansion study to evaluate the safety, tolerability, preliminary antitumor activity, PK, and pharmacodynamics of 2 dose levels of IK-175, administered PO in combination with nivolumab, in patients with primary PD-1-resistant metastatic or locally incurable, recurrent HNSCC for which standard therapy is no longer effective or is intolerable.
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
盲法说明
Open label study
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
- •Subject has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to
- •Subject has a histologically confirmed metastatic or locally incurable, recurrent HNSCC that has progressed within 12 weeks of initiation of PD-1 inhibitor agent, whether it was administered alone or in combination with chemotherapy.
- •Tumors must express PD-L1 with a minimum CPS ≥
- •Subjects can be enrolled regardless of their tumor's expression of human papillomavirus (HPV).
- •Subjects are required to have received prior treatment with a platinum-based chemotherapy in the recurrent or metastatic disease setting, unless medically contraindicated.
- •Subject has at least 1 measurable lesion per RECIST v1.
排除标准
- •Subject has untreated or symptomatic central nervous system (CNS) tumors or brain metastases.
- •Subject must have recovered to ≤ Grade 1 from clinically significant AEs related to prior therapy (eg, myelosuppression or renal or hepatic dysfunction.)
- •Subject has received prior treatment with an AHR inhibitor.
- •Subject has a medical condition that limits oral administration or impairment of gastrointestinal function that is expected to significantly reduce the absorption of IK-
- •Uncontrolled or life-threatening symptomatic concomitant disease.
- •Clinically significant cardiovascular disease as defined in the protocol.
- •Subject is on a medication that is a sensitive substrate of CYP2C8, 2C9, 2C19, or 3A4 that cannot be substituted.
- •Females who are pregnant or breastfeeding.
- •Other inclusion/exclusion criteria are listed in the protocol.
研究组 & 干预措施
Cohort 1
600 mg qd PO IK-175 + nivolumab
干预措施: IK-175 + nivolumab (Drug)
Cohort 2
450 mg q12h PO IK-175 + nivolumab
干预措施: IK-175 + nivolumab (Drug)
结局指标
主要结局
Frequency and severity of treatment related adverse events (TRAEs) in subjects receiving IK-175 in combination with nivolumab [Safety and Tolerability]
时间窗: Treatment Period (Approximately 18 months)
Number and severity of TRAEs as assessed by CTCAE 5.0
Frequency and severity of adverse events leading to dose modifications and/or treatment discontinuation in subjects receiving IK-175 in combination with nivolumab [Safety and Tolerability]
时间窗: Study Treatment Period (Approximately 18 months)
Number and severity of adverse events leading to dose modifications and/or treatment discontinuation as assessed by CTCAE 5.0
Preliminary antitumor activity of IK-175 treatment in combination with nivolumab: Objective response rate (ORR)
时间窗: Through study completion including the Treatment Period (approximately 18 months) and the Follow-Up Period (Up to 6 months)
ORR is defined as the percentage of participants with confirmed complete response (cCR) or confirmed partial response (cPR) per RECIST 1.1
Preliminary antitumor activity of IK-175 treatment in combination with nivolumab: Duration of response (DOR)
时间窗: Through study completion including the Treatment Period (approximately 18 months) and the Follow-Up Period (Up to 6 months))
DOR is defined as the time from the first documented CR or PR per RECIST 1.1 until disease progression or death from any cause
Frequency and severity of treatment emergent adverse events (TEAEs) in subjects receiving IK-175 in combination with nivolumab [Safety and Tolerability]
时间窗: Treatment Period (Approximately 18 months)
Number and severity of TEAEs as assessed by CTCAE 5.0
Frequency and severity of serious adverse events (SAEs) in subjects receiving IK-175 in combination with nivolumab [Safety and Tolerability]
时间窗: Treatment Period (Approximately 18 months)
Number and severity of SAEs as assessed by CTCAE 5.0
Preliminary antitumor activity of IK-175 treatment in combination with nivolumab: Disease control rate (DCR)
时间窗: Through study completion including the Treatment Period (approximately 18 months) and the Follow-Up Period (Up to 6 months)
DCR is defined as the percentage of participants with no occurrence of progressive disease with either cCR, cPR, or stable disease \[SD\] ≥ 16 weeks per RECIST 1.1 from the beginning of study therapy
次要结局
- PK of IK-175 when administered in combination with nivolumab: minimum serum concentration (Cmin)(Time Frame: Day 1, 2, 15 of Cycle 1, Day 1 of Cycles 2-3 (every 28 days), followed by Day 1 of every even cycle beginning with cycle 4 (every 56 days) through end of treatment (approximately 18 months))
- Preliminary antitumor activity of IK-175 in combination with nivolumab: Progression-free survival (PFS) median and at 6 months(Through study completion including the Treatment Period (approximately 18 months) and the Follow-Up Period (Up to 6 months))
- Preliminary antitumor activity of IK-175 in combination with nivolumab: Overall survival (OS), median and at 6 months(Through study completion including the Treatment Period (approximately 18 months) and the Follow-Up Period (Up to 12 months))
- PK of IK-175 when administered in combination with nivolumab: maximum serum concentration (Cmax)(Time Frame: Day 1, 2, 15 of Cycle 1, Day 1 of Cycles 2-3 (every 28 days), followed by Day 1 of every even cycle beginning with cycle 4 (every 56 days) through end of treatment (approximately 18 months))
- PK of IK-175 when administered in combination with nivolumab: area under the plasma concentration-time curve (AUC)(Time Frame: Day 1, 2, 15 of Cycle 1, Day 1 of Cycles 2-3 (every 28 days), followed by Day 1 of every even cycle beginning with cycle 4 (every 56 days) through end of treatment (approximately 18 months))
- Pharmacokinetics (PK) of IK-175 when administered in combination with nivolumab: half-life (t1/2)(Time Frame: Day 1, 2, 15 of Cycle 1, Day 1 of Cycles 2-3 (every 28 days), followed by Day 1 of every even cycle beginning with cycle 4 (every 56 days) through end of treatment (approximately 18 months))