A Phase I, Open-label, Multi-center Study of KFA115 as a Single Agent and in Combination With Pembrolizumab in Patients With Select Advanced Cancers
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 126
- 试验地点
- 24
- 主要终点
- Incidence and severity of adverse events (AEs) and serious adverse events (SAEs)
研究概览
简要总结
The purpose of this study is to characterize the safety and tolerability of KFA115 and KFA115 in combination with pembrolizumab in patients with select advanced cancers, and to identify the maximum tolerated dose and/or recommended dose.
详细描述
This is a phase I, open-label, multi-center study of KFA115 as a single agent and in combination with pembrolizumab. The study consists of a dose escalation part, followed by dose expansion part(s) for single-agent KFA115 and KFA115 in combination with pembrolizumab. The escalation parts will characterize safety and tolerability. After the determination of the maximum tolerated dose (MTD) / recommended dose (RD), the dose expansion parts will assess the preliminary anti-tumor activity in defined patient populations and further assess the safety and tolerability at MTD/RD.
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 100 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Non-small cell lung cancer with historic PD-L1 ≥ 1%, as determined locally using a clinically accepted assay. Patients must have experienced benefit from previous anti-PD(L)1-containing therapy for at least 4 months based on investigator-assessed disease stability or response prior to developing documented disease progression. Patients must have also received prior platinum-based chemotherapy, either in combination or in sequence with anti-PD-(L)1, unless patient was ineligible to receive such treatment.
- •Renal cell carcinoma, clear cell histology, previously treated with anti-PD(L)1-containing therapy and a VEGF targeted therapy as monotherapy or in combination. Patients should have documented disease progression following anti-PD(L)1-containing therapy.
- •Cutaneous melanoma, previously treated with anti-PD(L)1-containing therapy. Patients should have documented disease progression following anti-PD(L)1-containing therapy. Patients with BRAF V600-mutant melanoma must have also received prior therapy with a BRAF V600 inhibitor, with or without a MEK inhibitor.
- •Ovarian cancer, high-grade serous histology, naïve to anti-PD(L)1 therapy, must have received one prior systemic therapy in platinum-resistant setting.
- •Nasopharyngeal carcinoma, non-keratinizing locally advanced recurrent or metastatic. Depending on the study arm, patients may be naïve to anti-PD(L)1 therapy, or previously treated with platinum-based chemotherapy with or without anti-PD-(L)
- •Locally advanced unresectable or metastatic triple negative breast cancer, ovarian cancer (high-grade serous histology), anal cancer (squamous), MSI-H CRC, esophagogastric cancer, mesothelioma, and HNSCC.
- •Locally advanced unresectable or metastatic anal cancer (squamous), thymic carcinoma, MSI-H CRC, esophagogastric cancer, mesothelioma, and HNSCC, all naïve to anti-PD(L)1 therapy and for whom anti PD(L)1 therapy is not available.
- •Triple negative breast cancer with historic PD-L1 CPS ≥ 1%, must have received at least one line of chemotherapy. In addition, these patients must have previously received sacituzumab govitecan, and in the case of a BRCA mutation a PARP inhibitor, if these treatments are locally approved and accessible to the patient.
排除标准
- •Impaired cardiac function or clinically significant cardiac disease.
- •Use of agents known to prolong the QT interval unless they can be permanently discontinued for the duration of study.
- •History of severe hypersensitivity reactions to any ingredient of study drug(s) and other mAbs and/or their excipients.
- •Active, known or suspected autoimmune disease. Patients with vitiligo, type I diabetes, residual hypothyroidism only requiring hormone replacement, psoriasis not requiring systemic treatment or conditions not expected to recur may be considered. Patients previously exposed to anti-PD-1/PD-L1 treatment who are adequately treated for skin rash or with replacement therapy for endocrinopathies should not be excluded.
- •Any evidence of interstitial lung disease (ILD) or pneumonitis, or a prior history of ILD or non-infectious pneumonitis requiring high-dose glucocorticoids.
- •Patients who discontinued prior anti-PD-(L)1 therapy due to an anti-PD-(L)1-related toxicity (applicable to the KFA115 in combination with pembrolizumab treatment arms).
- •Patients with symptomatic peripheral neuropathy limiting instrumental activities of daily living.
- •Other protocol-defined inclusion/exclusion criteria may apply
研究组 & 干预措施
KFA115 + pembrolizumab
KFA115 + pembrolizumab combination given concurrently
干预措施: pembrolizumab (Drug)
Single-agent KFA115
KFA115 monotherapy
干预措施: KFA115 (Drug)
KFA115 run-in (1 cycle) + pembrolizumab
1-cycle KFA115 run-in followed by addition of pembrolizumab
干预措施: KFA115 (Drug)
KFA115 run-in (1 cycle) + pembrolizumab
1-cycle KFA115 run-in followed by addition of pembrolizumab
干预措施: pembrolizumab (Drug)
KFA115 + pembrolizumab
KFA115 + pembrolizumab combination given concurrently
干预措施: KFA115 (Drug)
结局指标
主要结局
Incidence and severity of adverse events (AEs) and serious adverse events (SAEs)
时间窗: 35 months
Incidence and severity of adverse events and serious adverse events, including changes in laboratory values, vital signs, and electrocardiograms qualifying and reported as AEs
Incidence and severity of dose limiting toxicities (DLTs) during the DLT evaluation period of single-agent KFA115 (dose escalation only)
时间窗: 28 days
A DLT is defined as an adverse event or abnormal laboratory value that occurs during the DLT evaluation period where the relationship to study treatment cannot be ruled out, and is not primarily related to disease, disease progression, intercurrent illness, or concomitant medications and meets the criteria defined in the study protocol
Incidence and severity of dose limiting toxicities (DLTs) during the DLT evaluation period of KFA115 in combination with pembrolizumab (dose escalation only)
时间窗: 28 days
A DLT is defined as an adverse event or abnormal laboratory value that occurs during the DLT evaluation period where the relationship to study treatment cannot be ruled out, and is not primarily related to disease, disease progression, intercurrent illness, or concomitant medications and meets the criteria defined in the study protocol
Frequency of dose interruptions, reductions
时间窗: 35 months
Number of dose interruptions of KFA115 and pembrolizumab, and number of dose reductions of KFA115
Dose intensity
时间窗: 35 months
Dose intensity of KFA115 and pembrolizumab is defined as the ratio of actual cumulative dose received and actual duration of exposure
次要结局
- Duration of response (DOR) per RECIST v1.1(35 months)
- Area under the concentration time curve (AUC) of KFA115 or pembrolizumab(During the first 168 days of treatment for single-agent KFA115 and 35 months for KFA115 in combination with pembrolizumab)
- Progression free survival (PFS) per RECIST v1.1(35 months)
- Peak plasma or serum concentration (Cmax) of KFA115 or pembrolizumab(During the first 168 days of treatment for single-agent KFA115 and 35 months for KFA115 in combination with pembrolizumab)
- Time to progression (TTP) per RECIST v1.1(35 months)
- Elimination half-life (T1/2) of KFA115 or pembrolizumab(During the first 168 days of treatment for single-agent KFA115 and 35 months for KFA115 in combination with pembrolizumab)
- Time to reach peak plasma or serum concentration (Tmax) of KFA115 or pembrolizumab(During the first 168 days of treatment for single-agent KFA115 and 35 months for KFA115 in combination with pembrolizumab)
- Best overall response (BOR) per RECIST v1.1(35 months)
- Minimum plasma or serum concentration (Cmin) of KFA115 or pembrolizumab(During the first 168 days of treatment for single-agent KFA115 and 35 months for KFA115 in combination with pembrolizumab)