A Phase 2 Trial to Evaluate the Safety and Efficacy of NKT2152 in Combination With Palbociclib (Doublet) and With Palbociclib and Sasanlimab (Triplet) in Subjects With Advanced or Metastatic Clear Cell Renal Cell Carcinoma
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 18
- 试验地点
- 8
- 主要终点
- Number of Participants with Dose Limiting Toxicity (DLT) events during the DLT monitoring period (first 28 days of dosing) in the Lead-in Phase
研究概览
简要总结
The goal of the Lead-in phase of the study is to evaluate the safety, efficacy, pharmacokinetics (PK) and determine recommended dose for expansion (RDE) of NKT2152 in combination with palbociclib (Doublet) and with palbociclib and sasanlimab (Triplet) in subjects with advanced or metastatic clear cell renal cell carcinoma (ccRCC) who received prior therapy. The goal of the Expansion phase of the study is to evaluate the safety, efficacy, PK at the selected RDE and identify the RP2D for NKT2152 in combination with palbociclib (Doublet) and with palbociclib and sasanlimab (Triplet) in subjects with advanced or metastatic clear cell renal cell carcinoma (ccRCC) who received prior therapy.
详细描述
This is a Phase 2 open-label, multicenter, global study of NKT2152. This study is designed as two phases: a Lead-in phase and an Expansion phase. Patients must be 18 years or older, with advanced or metastatic clear cell renal cell carcinoma (ccRCC). Eligible patients must have progressed or relapsed after at least 1 prior anti-vascular endothelial growth factor (VEGF)/VEGF receptor (VEGFR) systemic therapy and 1 immune checkpoint inhibitor (ICI) for advanced or metastatic ccRCC alone or in combination.
The Lead-in phase is designed as a dose escalation phase to evaluate the safety, efficacy, pharmacokinetics (PK) and determine recommended dose for expansion (RDE) of NKT2152 in combination with palbociclib and sasanlimab in advanced or metastatic ccRCC patients who received prior therapy.
The subsequent Expansion phase will evaluate the safety, efficacy, PK at the selected RDE and identify the RP2D for NKT2152 in combination with palbociclib and sasanlimab in advanced or metastatic ccRCC patients who received prior therapy.
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
Randomization during Expansion phase
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
- •Must have locally advanced or metastatic ccRCC and have progressed or relapsed after at least 1 prior anti-VEGF/VEGFR systemic therapy and 1 ICI.
- •Measurable disease per the Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1)
- •KPS score of at least 70%
- •Able to swallow oral medications.
排除标准
- •Active CNS metastases and/or carcinomatous meningitis
- •Has had any major cardiovascular event within 6 months or clinically significant cardiovascular disease
- •Major surgery (eg, GI surgery, removal or biopsy of brain metastasis) within 3 months before administration of study drug.
- •Has known HIV
- •History of hepatitis B or known active hepatitis C infection
- •Has received prior treatment with NKT2152, other HIF2α inhibitors, other CDK 4/6 inhibitors, palbociclib, or sasanlimab
- •Radiation therapy for bone metastasis within 2 weeks, or any other external radiation therapy within 4 weeks before administration of the first dose of study treatment
- •Corrected QT interval calculated by Fridericia formula (QTcF) > 480 ms within 28 days prior to first dose
- •Hypoxia or requires intermittent or chronic supplemental oxygen or any chronic lung condition which has required supplemental oxygen in the past
- •Has a history of interstitial lung disease
- •Has any active or recent history of a known or suspected autoimmune disease
研究组 & 干预措施
Lead-in Doublet combination
Lead-in Doublet assesses safety of oral dosing NKT2152 at increasing dosage levels in combination with palbociclib to determine a recommended dose for expansion (RDE).
干预措施: NKT2152 (Drug)
Lead-in Doublet combination
Lead-in Doublet assesses safety of oral dosing NKT2152 at increasing dosage levels in combination with palbociclib to determine a recommended dose for expansion (RDE).
干预措施: palbociclib (Drug)
Lead-in Triplet combination
Lead-in Triplet assesses the safety of two doses of NKT2152 identified in the Doublet arm (RDE and RDE-1) by orally dosing ccRCC patients with NKT2152 in combination with palbociclib and sasanlimab
干预措施: NKT2152 (Drug)
Lead-in Triplet combination
Lead-in Triplet assesses the safety of two doses of NKT2152 identified in the Doublet arm (RDE and RDE-1) by orally dosing ccRCC patients with NKT2152 in combination with palbociclib and sasanlimab
干预措施: palbociclib (Drug)
Lead-in Triplet combination
Lead-in Triplet assesses the safety of two doses of NKT2152 identified in the Doublet arm (RDE and RDE-1) by orally dosing ccRCC patients with NKT2152 in combination with palbociclib and sasanlimab
干预措施: sasanlimab (Other)
Expansion Doublet combination
Subjects randomized to Arm 1 will receive the Doublet combination (NKT2152 in combination with palbociclib) to provide an assessment of anti-tumor activity and to determine the RP2D.
干预措施: NKT2152 (Drug)
Expansion Doublet combination
Subjects randomized to Arm 1 will receive the Doublet combination (NKT2152 in combination with palbociclib) to provide an assessment of anti-tumor activity and to determine the RP2D.
干预措施: palbociclib (Drug)
Expansion Triplet combination
Subjects randomized to Arm 2 will receive the Triplet therapy (NKT2152 in combination with palbociclib and sasanlimab) to provide an assessment of anti-tumor activity and to determine the RP2D.
干预措施: NKT2152 (Drug)
Expansion Triplet combination
Subjects randomized to Arm 2 will receive the Triplet therapy (NKT2152 in combination with palbociclib and sasanlimab) to provide an assessment of anti-tumor activity and to determine the RP2D.
干预措施: palbociclib (Drug)
Expansion Triplet combination
Subjects randomized to Arm 2 will receive the Triplet therapy (NKT2152 in combination with palbociclib and sasanlimab) to provide an assessment of anti-tumor activity and to determine the RP2D.
干预措施: sasanlimab (Other)
结局指标
主要结局
Number of Participants with Dose Limiting Toxicity (DLT) events during the DLT monitoring period (first 28 days of dosing) in the Lead-in Phase
时间窗: 28 days
DLTs graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5 .0.
Objective Response Rate (ORR) determined by the Investigator
时间窗: 1 years
ORR defined as the percentage of participants with a confirmed complete response (CR) or partial response (PR) based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
次要结局
- Overall Survival (OS)(2 years)
- Maximum observed plasma concentration (Cmax) of palbociclib(1 years)
- Observed trough concentration of sasanlimab (Ctrough)(1 years)
- Clinical Benefit Rate (CBR)(1 years)
- Number of Participants with Adverse Events(2 years)
- Maximum observed plasma concentration (Cmax) of NKT2152(1 years)
- Area under the plasma concentration time curve (AUC0-t) of NKT2152, and accumulation ratio (RAC)(1 years)
- Time to maximum observed plasma concentration of palbociclib (Tmax)(1 years)
- Area under the plasma concentration time curve (AUC0-t) of palbociclib, and accumulation ratio (RAC)(1 years)
- Maximum observed plasma concentration (Cmax) of sasanlimab(1 years)
- Progression-free survival (PFS)(2 years)
- Time to Response (TTR)(1 years)
- Duration of Response (DOR)(1 years)
- Time to maximum observed plasma concentration of NKT2152 (Tmax)(1 years)
- Observed trough concentration of NKT2152 (Ctrough)(1 years)
- Observed trough concentration of palbociclib (Ctrough)(1 years)