A Phase 1b Study of WU-NK-101 in Combination With Cetuximab for Advanced and/or Metastatic Colorectal Cancer (CRC) and Advanced and/or Metastatic Squamous Cell Carcinoma of the Head and Neck (SCCHN)
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 发起方
- Wugen, Inc.
- 入组人数
- 30
- 试验地点
- 2
- 主要终点
- Incidence of Adverse Events of WU-NK-101 in combination with cetuximab as assessed by by CTCAE v5
研究概览
简要总结
This study is a Phase 1b open-label study designed to characterize the safety, tolerability, and preliminary anti-tumor activity of WU-NK-101 in combination with cetuximab in patients with advanced and/or metastatic CRC (Cohort 1), and in patients with advanced and/or metastatic SCCHN (Cohort 2). The overall study will be comprised of two phases, a Dose Escalation Phase, and a Cohort Expansion Phase.
详细描述
In the Dose Escalation Phase, up to 12 patients with either advanced and/or metastatic CRC or advanced and/or metastatic SCCHN will be treated with WU-NK-101, alone and in combination with cetuximab, in successive cohorts of 3 to 6 patients using a standard 3 + 3 design. Intra-patient dose escalation is not permitted. Patients may receive up to one 8-week cycle of treatment. Each 8-week cycle is divided into two 28-day segments, (Segments A and B).
During Segment A, only WU-NK-101 (monotherapy) will be administered. Segment A will consist of two doses of WU-NK-101 infused on Day 1 and Day 15. Patients that do not experience a dose limiting toxicity (DLT) will proceed to Segment B.
During Segment B, WU-NK-101 will be administered in combination with cetuximab (combination therapy). WU-NK-101 cells will be administered on Days 30 and 44. Cetuximab will be administered on Days 29 and 43 at 500 mg/m2 (FDA-approved dose).
Once the MTD/MAD is defined in the Dose Escalation Phase, up to 9 additional patients will be enrolled in 2 parallel, disease specific, expansion cohorts (Cohort 1 [patients with CRC] and Cohort 2 [patients with SCCHN]) to further characterize the safety, tolerability, and preliminary anti-tumor activity of WU-NK-101 cells in combination with cetuximab. Patients will receive cetuximab dosed at 500 mg/m2 on Days 1 and 15, and WU-NK-101 on Days 2 and 16, in each 4-week cycle.
At the end of Cycle 2, patients who achieve a partial response (PR) or stable disease (SD) may receive up to 4 additional cycles of treatment of WU-NK-101 cells in combination with cetuximab with disease assessments on Day 28 (+/- 3 days) of each even numbered cycle, for a maximum of 6 cycles.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients must have a histologically confirmed diagnosis of advanced and/or metastatic CRC that has failed or progressed beyond first line or higher line standard of care therapy including bevacizumab combination, cetuximab combination, 5-FU based regimens, or checkpoint inhibitors alone or in combination. Patients must have received all targeted therapies for which they are eligible. Patients may be included in this study regardless of mutation status (e.g., RAS-mutant, wild-type, or unknown status, BRAF V600E, etc.) and EGFR expression.
- •Patients must have a histologically confirmed diagnosis of SCCHN that has failed or progressed beyond first or higher line standard of care therapy including cetuximab alone or in combination, checkpoint inhibitors alone and in combination, or regimens containing radiotherapy. Patients may be included in this study regardless of EGFR expression.
排除标准
- •Experienced toxicities related to prior cetuximab treatment which required permanent discontinuation of cetuximab per the current label.
研究组 & 干预措施
WU-NK-101 Monotherapy/Cetuximab combo Run-in
WU-NK-101 is a non-engineered Natural Killer (NK) cell derived from peripheral blood mononuclear cells (PBMC) that is cytokine-reprogrammed, expanded, and cryopreserved to create an allogeneic enhanced memory-like anti-tumor NK cell therapy product.
Each 8 week cycle in dose escalation is divided into two 28- days segments. Patients will receive WU-NK-101 (Days 1 and 15) in the first segment and a combination of cetuximab (500mg/m2 on Days 29 and 43) plus WU-NK-101 (Days 30 and 44) in the second segment.
干预措施: WU-NK-101 - Dose Escalation (Biological)
WU-NK-101 Monotherapy/Cetuximab combo Run-in
WU-NK-101 is a non-engineered Natural Killer (NK) cell derived from peripheral blood mononuclear cells (PBMC) that is cytokine-reprogrammed, expanded, and cryopreserved to create an allogeneic enhanced memory-like anti-tumor NK cell therapy product.
Each 8 week cycle in dose escalation is divided into two 28- days segments. Patients will receive WU-NK-101 (Days 1 and 15) in the first segment and a combination of cetuximab (500mg/m2 on Days 29 and 43) plus WU-NK-101 (Days 30 and 44) in the second segment.
干预措施: Cetuximab - Dose Escalation (Drug)
WU-NK-101 /Cetuximab Combo
Patients will receive cetuximab dosed at 500 mg/m2 on Days 1 and 15, and WU-NK-101 on Days 2 and 16, in each 4-week cycle. Depending on response patients may receive up to 6 cycles of treatment.
干预措施: WU-NK-101 - Cohort Expansion (Biological)
WU-NK-101 /Cetuximab Combo
Patients will receive cetuximab dosed at 500 mg/m2 on Days 1 and 15, and WU-NK-101 on Days 2 and 16, in each 4-week cycle. Depending on response patients may receive up to 6 cycles of treatment.
干预措施: Cetuximab - Cohort Expansion (Biological)
结局指标
主要结局
Incidence of Adverse Events of WU-NK-101 in combination with cetuximab as assessed by by CTCAE v5
时间窗: 24 months
Safety is based on evaluation of adverse events (AEs) and serious adverse events (SAEs) from the time of consent until the end of the study visit or at the end of treatment visit.
Maximum Tolerated Dose
时间窗: up to 56 days from first dose
Maximum tolerated or administered dose of WU-NK-101 in combination with cetuximab
次要结局
- Duration of Response(24 months)
- Overall Response Rate(24 months)