NCT06586957招募中1 期
A Phase 1, First-in-human, Open-label Study to Evaluate the Safety, Tolerability, PK, and Preliminary Anti-tumor Activity of the Novel Oral CDK2 Degrader NKT3964 in Adults With Advanced/Metastatic Solid Tumors
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 150
- 试验地点
- 30
- 主要终点
- Number of Participants with Dose Limiting Toxicity (DLT) events
研究概览
简要总结
The goal of the Dose Escalation phase of the study is to evaluate the safety, tolerability, pharmacokinetics (PK) and preliminary anti-tumor activity to determine the preliminary recommended dose for expansion (RDE) of NKT3964 in adults with advanced or metastatic solid tumors. The goal of the Expansion phase of the study is to evaluate the preliminary anti-tumor activity of NKT3964 at the RDE based on objective response rate (ORR) and determine the preliminary recommended Phase 2 dose (RP2D).
详细描述
Inclusion Criteria:
- Must have a pathologically confirmed, advanced and unresectable or metastatic solid tumor listed below with documented disease progression on last standard treatment.
For Part 1 only: Patients must be refractory to, or intolerant of existing therapy(ies) known to provide clinical benefit for their condition.
Part 1 Dose Escalation and Food Effect Sub-study:
- Ovarian cancer
- Endometrial cancer (only 'endometrioid' subtype requires CCNE1 amplification)
- Gastric, gastroesophageal junction (GEJ) or esophageal adenocarcinoma with CCNE1 amplification
- Small cell lung cancer (SCLC)
- Triple-negative breast cancer (TNBC; HER2, estrogen receptor and progesterone receptor negative)
- HR+ (includes estrogen-receptor or progesterone-receptor) and HER2- breast cancer (must have progressed following treatment with a CDK4/6 inhibitor, and is not suitable for endocrine therapy [ET])
- Other solid tumors with CCNE1 amplification
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
盲法说明
Randomized for the 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 a pathologically confirmed advanced and unresectable or metastatic solid tumor listed below with documented disease progression on last standard treatment. Part 1 only: subjects must be refractory to, or intolerant of existing therapy(ies) known to provide clinical benefit for their condition.
- •Dose Escalation:
- •Ovarian cancer
- •Endometrial cancer (only endometrioid subtype will require CCNE1 amplification)
- •Gastric, gastroesophageal junction (GEJ) or esophageal adenocarcinoma with CCNE1 amplification
- •Small cell lung cancer (SCLC)
- •Triple-negative breast cancer (TNBC; HER2, estrogen receptor and progesterone receptor negative)
- •HR+ (includes estrogen-receptor or progesterone-receptor) and HER2- breast cancer (must have progressed following treatment with a CDK4/6 inhibitor, and is not suitable for endocrine therapy [ET])
- •Other solid tumors with CCNE1 amplification
- •Dose Expansion:
- •Part 2A: HR+ and HER2- breast cancer that is locally advanced and unresectable (Stage III) or metastatic (Stage IV); previously treated with ≥1 line of standard of care (SOC) including CDK4/6 inhibitor plus ET and not suitable for further ET. Subjects must have progressed after receiving therapy for ≥3 months in the metastatic setting or for ≥6 months in the adjuvant setting. Subjects must have received ≤2 lines of systemic cytotoxic therapy (chemotherapy or cytotoxic antibody drug conjugate [ADC]) in the metastatic setting..
- •Part 2B: Advanced platinum-based-chemotherapy resistant or refractory epithelial ovarian/fallopian/primary peritoneal carcinoma or clear cell ovarian cancer (defined as recurrence ≤6 months after completing platinum-based regimen) with progression on at least one platinum containing therapy and previously treated with ≤4 prior lines of systemic therapy administered for advanced/metastatic disease and with CCNE1 amplification.
- •Part 2C: Advanced unresectable or metastatic gastric, GEJ or esophageal adenocarcinoma with progression on at least one systemic therapy and previously treated with ≤3 prior lines of systemic therapy administered for advanced/metastatic disease, with CCNE1 amplification as determined by NGS by local liquid or tissue test.
- •Part 2D: Advanced endometrial adenocarcinoma or uterine papillary serous carcinoma previously treated with ≤4 prior lines of systemic therapy administered for advanced/metastatic disease with CCNE1 amplification.
- •Part 2E: Advanced/recurrent uterine carcinosarcoma previously treated with 1 prior platinum-based chemotherapy regimen and ≤3 prior lines of systemic therapy. Prior bevacizumab or PARP inhibitors are allowed and must be at least 3 weeks prior to the start of study drug.
- •Have adequate organ function
- •Subjects with female reproductive organs must be surgically sterile, post-menopausal, or must be willing to use highly effective method(s) of contraception
- •Ability to swallow oral medications.
- •Consent to provide archived tumor tissues and paired tumor biopsy at pretreatment
排除标准
- •Locally advanced solid tumor that is a candidate for curative treatment through radical surgery and/or radiotherapy, or chemotherapy.
- •History of another malignancy with exceptions
- •History of lymphohistiocytic or lymphoid hyperplasia; hemophagocytic lymphohistiocytosis.
- •Failed to recover from effects of prior anticancer treatment therapy to baseline or Grade ≤ 1 severity (per CTCAE)
- •Clinically significant cardiovascular event within 6 months prior to start of NKT3964 treatment
- •Known active CNS metastases and/or carcinomatous meningitis
- •Active interstitial lung disease currently requiring treatment
- •History of uveitis, retinopathy or other clinically significant retinal disease
- •Active or chronic corneal disorders, other active ocular conditions requiring ongoing therapy, or any clinically significant corneal disease
- •Active wound healing from major surgery within 1 month or minor surgery within 10 days before the first dose of NKT
- •Known human immunodeficiency virus (HIV), active hepatitis B or C infection
- •Prior investigative treatment with a selective or nonselective CDK2 inhibitor or degrader
- •Childs-Pugh class B or C cirrhosis or any other clinically significant liver disorder
- •Palliative radiation therapy within 14 days or other radiation therapy within 4 weeks prior to C1D1
研究组 & 干预措施
Dose Escalation
Experimental
Dose escalation will assess the safety, efficacy, and PK/PD data of oral dosing NKT3964 at increasing dosage levels to determine the MTD and/or preliminary RDEs.
干预措施: NKT3964 (Drug)
Dose Expansion
Experimental
Dose expansion will include the RDE selected to determine the preliminary antitumor activity and the RP2D.
干预措施: NKT3964 (Drug)
结局指标
主要结局
Number of Participants with Dose Limiting Toxicity (DLT) events
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)
时间窗: 1 Year
ORR defined as the percentage of participants with a confirmed complete response (CR) or partial response (PR) by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) as determined by the Investigator
次要结局
- Progression-free survival (PFS)(2 Year)
- Duration of Response (DOR)(2 Year)
- Disease control rate(1 Year)
- Overall Survival (OS)(2 Year)
- Time to Response (TTR)(1 Year)
- Number of Participants with Adverse Events(2 Year)
- Observed trough concentration of NKT3964 (Ctrough)(88 Weeks)
- Progression-free survival (PFS)(2 Year)
- Duration of Response (DOR)(2 Year)
- Disease control rate(1 Year)
- Overall Survival (OS)(2 Year)
- Time to Response (TTR)(1 Year)
- Number of Participants with Adverse Events(2 Year)
- Maximum observed plasma concentration (Cmax) of NKT3964 with and without a high-fat and/or low-fat meal(1 Month)
- Time to maximum observed plasma concentration of NKT3964 (Tmax) with and without a high-fat and/or low-fat meal(1 Month)
- Observed trough concentration of NKT3964 (Ctrough)(88 Weeks)
- Area under the plasma concentration-time curve (AUC0-t) of NKT3964 with and without a high-fat and/or low-fat meal(1 Month)
- Apparent clearance (CL/F) of NKT3964(1 Month)
- Apparent volume of distribution (V/F) of NKT3964(1 Month)
- Half-life (t1/2) of NKT3964(1 Month)
- Accumulation ratio (AR) of NKT3964(1 Month)
研究者
研究点 (30)
Loading locations...
相似试验
终止
1 期
A Study With NKT3447 for Adults With Advanced/Metastatic Solid TumorsSolid TumorSolid Tumor, AdultAdvanced Solid TumorMetastatic TumorOvarian NeoplasmsOvarian CarcinomaMetastatic Ovarian CarcinomaEndometrial CancerEndometrial NeoplasmsOvarian CancerEndometrial DiseasesMetastatic Endometrial CancerMetastatic Endometrial CarcinomaAdvanced Endometrial CarcinomaAdvanced Ovarian CarcinomaAdvanced Gastric CarcinomaMetastatic Gastric CancerMetastatic Gastric CarcinomaSmall-cell Lung CancerSmall Cell Lung CarcinomaTriple Negative Breast CancerTriple Negative Breast NeoplasmsPlatinum-resistant Ovarian CancerPlatinum-refractory Ovarian CarcinomaCCNE1 AmplificationHormone Receptor Negative Breast CarcinomaHuman Epidermal Growth Factor 2 Negative Carcinoma of BreastProgesterone-receptor-positive Breast CancerGastric CancerNCT06264921NiKang Therapeutics, Inc.23
已完成
1 期
Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of UB-221 as an Add-on Therapy in CSU PatientsUrticaria ChronicNCT03632291United BioPharma15
尚未招募
1 期
Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Immunogenicity of UB-221 in Healthy VolunteersChronic Spontaneous UrticariaNCT04404023UBP Greater China (Shanghai) Co., Ltd15
撤回
1 期
PF-07225570 Alone or in Combination With an Anti-PD-1 Antibody in Recurrent Non-muscle Invasive Bladder Cancer (NMIBC)Bladder CancerNCT05259397Pfizer
已完成
1 期
A Study Evaluating the Safety, Tolerability, and Initial Efficacy of Recombinant Human Anti-T-cell Immunoreceptor With Ig and ITIM Domains (TIGIT) Monoclonal Antibody Injection (IBI939) in Subjects With Advanced Malignant TumorsAdvanced MalignanciesNCT04353830Innovent Biologics (Suzhou) Co. Ltd.34