NCT05128487进行中（未招募）1 期
A Phase 1/2, Open-label Study to Investigate the Safety, Tolerability, Pharmacokinetics, and Preliminary Antitumor Activity of NDI-101150 Administered as Monotherapy or in Combination With Pembrolizumab in Patients With Solid Tumors
Nimbus Saturn, Inc.18 个研究点 分布在 1 个国家目标入组 106 人开始时间: 2021年11月5日最近更新:
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 106
- 试验地点
- 18
- 主要终点
- Part 1: Frequency of dose-limiting toxicities (DLTs)
研究概览
简要总结
This study is to determine the maximum tolerated dose (MTD) and the recommended Phase 2 dose (RP2D) and to investigate the safety, pharmacokinetics (PK), pharmacodynamics, and preliminary antitumor activity of NDI-101150 given as monotherapy or in combination with pembrolizumab in adult patients with advanced solid tumors.
详细描述
This is a multicenter, open-label, first-in-human, Phase 1/2 study.
The study will consist of 2 phases:
- The Dose Escalation Phase: designed to evaluate the safety and tolerability of NDI-101150 as monotherapy (Arm 1) and in combination with pembrolizumab (Arm 2) in patients with advanced solid tumors.
- The Dose Expansion Phase: designed to evaluate the safety and efficacy of NDI-101150 as monotherapy (Arm 1) and in combination with pembrolizumab (Arm 2) in disease-specific dose expansion cohorts: gastric and gastroesophageal junction [GEJ] cancer, non-small cell lung cancer [NSCLC], and renal cell carcinoma [RCC].
Each phase of the study will consist of 3 periods:
- A Screening period of up to 28 days during which patient eligibility will be reviewed and approved by the Sponsor.
- Treatment period that will extend from Cycle 1 Day 1 until progression of disease (PD), unacceptable toxicity, withdrawal of consent, start of a new systemic anticancer treatment, discontinuation of the patient by the Investigator, or termination of the study by the Sponsor. This will also include Safety Follow-up Visit 30 days [+3 days] after the last dose of investigational medicinal product.
- Post treatment Follow-up period which will continue until lost to follow-up, withdrawal of consent, or the End of the Study (whichever comes first).
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
- •Life expectancy of ≥ 12 weeks
- •Measurable or non-measurable disease for Dose Escalation; measurable disease using RECIST v1.1 is required for Dose Expansion
- •Recovered from prior therapy to Grade ≤ 1 or return to baseline status (except for alopecia)
- •Eastern Cooperative Oncology Group (ECOG) performance status 0-1
- •Patients with adequate bone marrow, kidney and liver function
- •Last dose of previous anticancer therapy ≥ 4 weeks prior to first dose of NDI-101150; includes prior anti-PD-1 or anti-PD-L1 therapy, other anticancer therapy, radiotherapy, or surgical intervention
- •For Dose Escalation Phase Only (Dose Escalation, Monotherapy and Combination Therapy): Histologically or cytologically confirmed advanced or metastatic solid tumors for whom no standard therapies are available or refractory to standard therapy
- •For Dose Expansion Phase (Dose Expansion, Monotherapy and Combination Therapy): Willing to consent to required tumor biopsy(ies). Histologically or cytologically confirmed advanced or metastatic G/GEJ, NSCLC or RCC for which no standard therapy is available or are refractory to standard therapy
排除标准
- •Previous solid organ or hematopoietic cell transplant
- •Central nervous system (CNS) malignant disease not previously treated, active leptomeningeal disease, uncontrolled symptomatic CNS involvement, or CNS malignant disease requiring steroid or other therapeutic intervention
- •Prior anticancer therapy within 2-6 weeks of trial start (depending on nature of therapy).
- •Clinically significant cardiovascular disease
- •History of severe hypersensitivity reaction to treatment with monoclonal antibody(ies) (for combination therapy cohorts only)
- •History of interstitial lung disease, idiopathic pulmonary fibrosis, pneumonitis (including drug induced), organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic organizing pneumonia, etc.), or evidence of history of pneumonitis on chest computed tomography scan in the last 6 months
- •Known additional malignancy that is active and/or in progression requiring treatment
- •Unstable or severe uncontrolled medical condition (e.g., unstable cardiac function, unstable pulmonary condition, uncontrolled diabetes, thromboembolic event within the past 3 months) or any important medical or psychiatric illness or abnormal laboratory finding
- •Unable to discontinue medications that are strong inducers or inhibitors of CYP3A4 and/or CYP2C8
- •History of severe irAE that led to permanent discontinuation of prior immunotherapy
- •History of recent Grade >/= 3 irAE or any Grade 4 life-threatening irAE, neurologic or ocular AE of any grade while receiving prior immunotherapy
- •NOTE: Other protocol defined Inclusion and Exclusion criteria may apply.
研究组 & 干预措施
NDI-101150 (Monotherapy)
Experimental
Patients in escalation and expansion, will receive NDI-101150 capsules orally once daily continuously in 4-week cycles (28 days).
干预措施: NDI-101150 (Drug)
NDI-101150-Pembrolizumab (Combination therapy)
Experimental
Patients in escalation and expansion phase, will receive NDI-101150 capsules orally once daily continuously in 3-week cycles (21 days), along with pembrolizumab via intravenous (IV) infusion at a dose of 200 mg every 3 weeks.
干预措施: NDI-101150 (Drug)
NDI-101150-Pembrolizumab (Combination therapy)
Experimental
Patients in escalation and expansion phase, will receive NDI-101150 capsules orally once daily continuously in 3-week cycles (21 days), along with pembrolizumab via intravenous (IV) infusion at a dose of 200 mg every 3 weeks.
干预措施: Pembrolizumab (Drug)
结局指标
主要结局
Part 1: Frequency of dose-limiting toxicities (DLTs)
时间窗: Cycle 1 (28 days)
Part 2: Objective response rate (ORR)
时间窗: Up to approximately 34 months
次要结局
- Part 1 and Part 2: Duration of response (DOR)(Time from first response until confirmed PD (Assessed up to 37 months))
- Part 2: Overall survival(Assessed up to 37 months)
- Part 1 and Part 2: Number of patients with adverse events (AEs) and Serious adverse events (SAEs)(From Screening (Day -28 to Day -1) until safety follow-up (>30 days after last dose) [Assessed up to 37 months])
- Part 1 and Part 2: Maximum plasma concentration (Cmax) of NDI-101150(Cycle 1 Day 1, Cycle 2 Day 1, Cycle 1 Day 2, Cycle 2 Day 2 (Monotherapy); at EOT (end-of-treatment)/ET (early termination) [Cycle length is 28 days for monotherapy and 21 days for combination therapy] (Up to 37 months))
- Part 1 and Part 2: Time to maximum plasma concentration (tmax) of NDI-101150(Cycle 1 Day 1, Cycle 2 Day 1, Cycle 1 Day 2, Cycle 2 Day 2 (Monotherapy); at EOT (end-of-treatment)/ET (early termination) [Cycle length is 28 days for monotherapy and 21 days for combination therapy] (Up to 37 months))
- Part 1 and Part 2: Area under the concentration-time curve from time zero to the last observable concentration (AUC0-t) of NDI-101150(Cycle 1 Day 1, Cycle 2 Day 1, Cycle 1 Day 2, Cycle 2 Day 2 (Monotherapy); at EOT (end-of-treatment)/ET (early termination) [Cycle length is 28 days for monotherapy and 21 days for combination therapy] (Up to 37 months))
- Part 1 and Part 2: Area under the concentration-time curve extrapolated to infinity (AUC0-∞) of NDI-101150(Cycle 1 Day 1, Cycle 2 Day 1, Cycle 1 Day 2, Cycle 2 Day 2 (Monotherapy); at EOT (end-of-treatment)/ET (early termination) [Cycle length is 28 days for monotherapy and 21 days for combination therapy] (Up to 37 months))
- Part 1: Objective response rate (ORR)(Assessed up to 37 months)
- Part 1 and Part 2: Time to response (TTR)(Time from first dose until first response (Assessed up to 37 months))
- Part 1 and Part 2: Progression-free survival (PFS)(From first dose until confirmed progression of disease (PD) or death (Assessed up to 37 months))
研究者
研究点 (18)
Loading locations...
相似试验
终止
1 期
Phase 1/2 Study of OBI-999 in Patients With Advanced Solid TumorsLocally Advanced Solid TumorNCT04084366OBI Pharma, Inc44
终止
1 期
A Safety and Efficacy Study of INC280 Alone, and in Combination With Erlotinib, Compared to Chemotherapy, in Advanced/Metastatic Non-small Cell Lung Cancer Patients With EGFR Mutation and cMET AmplificationNon-Small Cell Lung CancerNCT02468661Novartis Pharmaceuticals23
终止
1 期
A Study of HLX06, a Humanized Monoclonal Antibody Targeting Human Vascular Endothelial Growth Factor Receptor-2 in Patients With Advanced Solid TumorsSolid Tumor, AdultNCT03494231Henlix, Inc5
已完成
1 期
A Study of Tucatinib (ONT-380) Combined With Capecitabine and/or Trastuzumab in Patients With HER2+ Metastatic Breast CancerHER2 Positive Metastatic Breast CancersNCT02025192Seagen Inc.60
终止
1 期
E7080 in Combination With Carboplatin + Gemcitabine Versus Carboplatin + Gemcitabine Alone as Second Line Therapy in Patients With Platinum-Sensitive Recurrent Ovarian Cancer by CA125Ovarian CancerNCT01133756Eisai Inc.7
相关资讯
HPK1 Inhibitors Show Promise in Enhancing Immunotherapy for Solid Tumors• HPK1 inhibition is emerging as a strategy to enhance T-cell functionality and improve immunotherapy efficacy in solid tumors, with several inhibitors in early-phase trials.
• NDI-101150, a novel oral HPK1 inhibitor, has demonstrated early clinical efficacy, including a complete response in renal cell carcinoma, as both a monotherapy and in combination with pembrolizumab.
• Combination therapies involving HPK1 inhibitors like BGB-15025 with checkpoint inhibitors such as tislelizumab are showing early efficacy signals, warranting further investigation.
• Several HPK1 inhibitors, including GRC 54276 and CFI-402411, are in phase 1/2 trials, exploring their potential as monotherapies and in combination with pembrolizumab across various advanced solid tumors.last yearNimbus Therapeutics' HPK1 Inhibitor Shows Promise in Advanced Renal Cell Carcinoma- NDI-101150 monotherapy achieved an 18% objective response rate in heavily pretreated renal cell carcinoma (RCC) patients who had prior exposure to checkpoint inhibitors.
- The clinical benefit rate was 29%, and the disease control rate was 65% in RCC patients treated with NDI-101150 monotherapy, indicating potential for durable responses.
- The Phase 1/2 trial data demonstrated an acceptable safety profile across an expanded population of 88 patients, supporting further clinical evaluation.
- Clinical samples revealed broad immune system activation across multiple cell types, reinforcing HPK1's proposed mechanism of action in enhancing anti-tumor immunity.last yearNimbus Therapeutics' HPK1 Inhibitor Shows Promise in Advanced Solid Tumors• NDI-101150 monotherapy achieved an 18% objective response rate in heavily pretreated renal cell carcinoma (RCC) patients who had prior exposure to checkpoint inhibitors.
• The clinical benefit rate was 29%, and the disease control rate reached 65% in RCC patients treated with NDI-101150 monotherapy.
• The Phase 1/2 trial data demonstrated broad immune system activation across multiple cell types, supporting the proposed mechanism of action for HPK1 inhibition.
• NDI-101150 maintained an acceptable safety profile across an expanded population of 88 patients in the ongoing Phase 1/2 clinical trial.last year