A First-In-Human, Phase 1/2 Study Of CFI-402411, a Hematopoietic Progenitor Kinase-1 (HPK1) Inhibitor, as a Single Agent and in Combination With Pembrolizumab in Subjects With Advanced Solid Malignancies
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 170
- 试验地点
- 13
- 主要终点
- To examine best overall response rate in subjects treated at multiple dose levels of CFI-402411.
研究概览
简要总结
The purpose of this study is to test the safety of an investigational drug called CFI-402411 alone and in combination with pembrolizumab and to study its effects in patients with advanced solid tumors who have progressed following previous therapies.
详细描述
This study will be a first-in-human study evaluating the safety and tolerability of CFI-402411 in subjects with advanced solid malignancies, when CFI-402411 is administered as a single agent or in combination with pembrolizumab. CFI-402411 is an oral pill that blocks the function of HPK1. Blocking HPK1 could stimulate an immune response against the tumor in patients. This immune response could be further enhanced when combined with pembrolizumab. The data obtained from this study will determine the dose and schedule and subject selection for further clinical studies.
Pre-clinical findings support further development of CFI-402411 as a novel anti-cancer agent, and the combination of CFI-402411 with pembrolizumab as a potential strategy to improve outcomes of subjects with advanced malignancies.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 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
- •Study-Wide Eligibility (Across All Study Parts):
- •Age > 18 years old
- •Have progressed after ≥ 1, but no more than 3 regimens of systemic therapies for recurrent / metastatic disease.
- •Subjects must have measurable disease.
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- •Part A1: Monotherapy Dose Escalation Inclusion Criteria
- •Histological or cytological confirmation of advanced solid malignancy that is refractory to or not a candidate for current standard treatment(s) and for whom no standard therapy is available.
- •Part A2: Biomarker-Focused Monotherapy Backfills Inclusion Criteria
- •Histological or cytological confirmation of one of the advanced cancers listed below;
- •cutaneous melanoma
- •Merkel cell carcinoma
- •squamous cell carcinoma of head and neck, anal canal, or skin
- •urothelial cancer
- •clear cell or non-clear cell renal cell carcinoma
- •triple negative breast cancer
- •endometrial cancer (regardless of MSI status)
- •cervical cancer
- •gastroesophageal cancer
- •hepatocellular cancer
- •any histology if known to be microsatellite-instability high (MSI-H)
- •Tumors must be refractory to or not a candidate for current standard treatment(s) and for whom no standard therapy exists.
- •Part A3: Monotherapy Expansion Inclusion Criteria
- •Histological or cytological confirmation of one of the advanced cancers listed below;
- •NSCLC cancer any histology
- •cutaneous melanoma
- •Merkel cell carcinoma
- •squamous cell carcinoma of head and neck, anal canal, or skin
- •urothelial cancer
- •clear cell or non-clear cell renal cell carcinoma
- •triple negative breast cancer
- •endometrial cancer (regardless of MSI status)
- •cervical cancer
- •gastroesophageal cancer
- •hepatocellular
- •any histology if known to be microsatellite-instability high (MSI-H)
- •Tumors must be refractory to or subjects intolerant of current standard treatment(s) and for whom no standard therapies are available.
- •Optional biopsies: Subjects that consent to optional fresh tumor biopsies must have at least one non-target soft tissue tumor lesion that can be biopsied.
- •Part B1: CFI-402411 in Combination with Pembrolizumab Dose Escalation Inclusion Criteria
- •Subjects must be deemed eligible by the Investigator to receive pembrolizumab.
- •Histological or cytological confirmation of one of the advanced cancers listed below (list may vary in each country, USA shown here);
- •NSCLC cancer any histology
- •cutaneous melanoma
- •Merkel cell carcinoma
- •squamous cell carcinoma of head and neck, anal canal, or skin
- •urothelial cancer
- •clear cell or non-clear cell renal cell carcinoma
- •triple negative breast cancer
- •endometrial cancer (regardless of MSI status)
- •cervical cancer
- •gastroesophageal cancer
- 另有 18 项未显示
排除标准
- •Study-Wide Eligibility (Across All Study Parts)
- •Subjects will be excluded from the study if any of the following criteria is met;
- •Previous treatment with an HPK1 inhibitor in other clinical trials.
- •Diagnosis of autoimmune-based disease or clinically significant auto-immune disorders.
- •Have symptomatic congestive heart failure, active angina pectoris or recent myocardial infarction (within 6 mos).
- •Have chronic atrial fibrillation.
- •Known central nervous system metastasis.
- •Stroke or transient ischemic attack, or other ischemic events or thromboembolic events within 3 months of study enrollment.
- •A history of QTc prolongation or a marked baseline prolongation of QT/QTc interval or a history of additional risk factors for TdP (e.g., heart failure, hypokalemia, family history of Long QT Syndrome).
研究组 & 干预措施
A1: Monotherapy Escalation
Dose escalation arm with CFI-402411. CFI-402411 is administered orally once daily.
干预措施: CFI-402411 (Drug)
A2: Monotherapy Biomarker
Dose escalation biomarker arm with CFI-402411. CFI-402411 is administered orally once daily.
干预措施: CFI-402411 (Drug)
A3: Monotherapy Expansion
Dose expansion arm with CFI-402411 at its recommended phase 2 dose.
干预措施: CFI-402411 (Drug)
B1: Combination Escalation
Dose escalation arm with CFI-402411 in combination with pembrolizumab (at its labeled dose and schedule).
干预措施: CFI-402411 (Drug)
B1: Combination Escalation
Dose escalation arm with CFI-402411 in combination with pembrolizumab (at its labeled dose and schedule).
干预措施: Pembrolizumab (Drug)
B2: Combination Expansion
Dose expansion arm with the recommended phase 2 dose of CFI-402411 in combination with pembrolizumab (at its labeled dose and schedule).
干预措施: CFI-402411 (Drug)
B2: Combination Expansion
Dose expansion arm with the recommended phase 2 dose of CFI-402411 in combination with pembrolizumab (at its labeled dose and schedule).
干预措施: Pembrolizumab (Drug)
结局指标
主要结局
To examine best overall response rate in subjects treated at multiple dose levels of CFI-402411.
时间窗: 48 months
Best overall response rate will be summarized by dose cohort and overall using the percent of patients in each tumor response category.
To examine progression free survival in subjects treated at multiple dose levels of CFI-402411.
时间窗: 48 months
Time from first dose to disease progression or death whichever occurs first will be calculated and summarized for all patients by dose cohort and overall.
To assess the incidence of adverse events of CFI-402411 as a single agent and at the recommended phase 2 dose (RP2D).
时间窗: 48 months
The number of subjects who experience an adverse event that was possibly related to study drug.
To assess the incidence of adverse events with CFI-402411 in combination with pembrolizumab and at the RP2D.
时间窗: 48 months
The number of subjects who experience an adverse event that was possibly related to study drug.
次要结局
- To further assess the incidence of adverse events of CFI-402411.(48 months)
- To assess duration of response of CFI-402411 monotherapy and in combination with pembrolizumab.(48 months)
- To evaluate the effect of CFI-402411 treatment on immune- or disease related biomarkers.(48 months)
- To identify the maximum tolerated dose of single agent CFI-402411 alone and in combination with pembrolizumab.(48 months)
- To assess the pharmacokinetic profile of CFI-402411 alone when it is administered in combination with pembrolizumab through AUC.(48 months)
- To assess the pharmacokinetic profile of CFI-402411 alone when it is administered in combination with pembrolizumab through Cmax.(48 months)
- To assess best overall response of CFI-402411 monotherapy and in combination with pembrolizumab.(48 months)
- To assess overall survival of CFI-402411 monotherapy and in combination with pembrolizumab.(48 months)
- To assess the pharmacokinetic profile of CFI-402411 alone when it is administered in combination with pembrolizumab through Tmax.(48 months)
- To assess the pharmacokinetic profile of CFI-402411 alone when it is administered in combination with pembrolizumab though Cmin.(48 months)
- To assess the pharmacokinetic profile of CFI-402411 alone when it is administered in combination with pembrolizumab through T1/2.(48 months)
- To assess overall response rates of CFI-402411 monotherapy and in combination with pembrolizumab.(48 months)
- To assess progression free survival of CFI-402411 monotherapy and in combination with pembrolizumab.(48 months)