NCT06614751尚未招募1 期
A Phase I, Open-label, Dose Escalation and Dose Expansion Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Preliminary Efficacy of DAT-2645 in Patients with Advanced/Metastatic Solid Tumors Harboring BRCA1/2 Loss of Function Alterations And/or Other Defects in the DNA Damage Repair Pathway
Danatlas Pharmaceuticals Co., Ltd2 个研究点 分布在 1 个国家目标入组 112 人开始时间: 2024年11月1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
- 尚未招募
- 发起方
- 入组人数
- 112
- 试验地点
- 2
- 主要终点
- Part 1, Dose esclalation study:To characterize the safety and tolerability of DAT-2645 monotherapy by evaluating the number of participants with dose limiting toxicities, adverse events, and laboratory abnormalities as graded by NCI CTCAE version 5.0
研究概览
简要总结
The primary objective of the study is to evaluate the safety, tolerability, PK, PD, and prilimary efficacy of DAT-2645 in patients with advanced/metastatic solid tumors harboring BRCA1/2 loss of function alterations and/or other defects in the DNA damage repair (DDR) pathway.
详细描述
This study will include Part 1 dose escalation study and Part 2 dose expansion study. 24 eligible patients will be enrolled into Part 1 and 88 eligible patients will be enrolled into Part 2.
In Part 1, 6 dose cohorts will be set and definte MTD/RDE. In Part 2, Dose optimization will be conducted firstly to definite RP2D. dose expansion will be conducted in another 2 cohorts to evaluate the efficacy.
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
- •Patients have provided informed consent prior to initiation of any procedures in this study.
- •At least 18 years of age (inclusive).
- •Evidence of an DDR deficiency status in tumor tissue determined by validated testing method. DDR deficiency is defined as one of the following results:
- •Deleterious or suspected deleterious mutations in germline or tumor BRCA1/2 genes
- •HRD positive
- •The detection performed in local lab is acceptable. The sample to detect BRCA mutation include blood, saliva, and oral mucosal epithelium. The sample of HRD detection is tumor tissue preferentially. Prior result is acceptable. Patients harboring BRCA, HRD ,or co-occurring BRCA/HRD mutations can be enrolled.
- •Part 1: Patients with advanced or metastatic solid tumor who have failed standard of care therapy, or are unable to tolerate standard of care therapy, or unable to obtain/unwilling to receive standard therapy. The tumor types will include those defined in Part 2 and other types.
- •Part 2: Patients with advanced or metastatic solid tumor (as specified below), regardless of PARP inhibitors were used or not in previous treatment.
- •Cohort A: patients who have HER2 (-), BRCA1/2 loss of function alternations or other HRD breast cancer, regardless of ER/PR status, and have failed at least 1st line of prior threatment.
- •Cohort B: patients who have HRD prostate cancer or pancreas cancer, and have failed standard of care therapy, or are unable to tolerate standard of care therapy, or unable to obtain/unwilling to receive standard therapy.
- •Cohort C: patients who have HRD colorectal cancer, gastric cancer, endometria cancer or other solid tumors, and have failed standard of care therapy, or are unable to tolerate standard of care therapy, or unable to obtain/unwilling to receive standard therapy.
- •At least one measurable lesion by RECIST v1.1 criteria.
- •Eastern Cooperative Oncology Group (ECOG) performance status score of 0~
- •Life expectancy of at least 3 months evaluated by the investigator.
- •Adequate hematologic and non-hematologic function during the screening.
- •Women of childbearing potential must have a negative result of serum pregnancy test at screening.
- •Women of childbearing potential or male patients whose spouse have childbearing potential must agree to use a reliable and effective method of contraception during the study and for 3 months after the last dose of the study drug.
排除标准
- •Patients who received systemic chemotherapy, small-molecule targeted drugs within 14 days or 5 half-lives (whichever is longer) prior to the first dose of study drug.
- •Patients who received biological anti-tumor drugs (including immunotherapy, target therapy, antibody-drug conjugate [ADC]) within 4 weeks prior to the first dose of the study drug.
- •Patients who have undergone major surgery within 4 weeks prior to the first dose of study drug.
- •Patients who have received radiotherapy within 4 weeks prior to the first dose of study drug (palliative radiotherapy for non-target lesions could be acceptable if it was performed before 14 days prior to the first dose of study drug).
- •Any previous treatment with a PARG inhibitor.
- •Patients with active CNS metastases (patients with asymptomatic CNS metastases which are imaging stable and not require steroid treatment within 28 days prior to the first dose of study drug, and previous treated breast cancer brain metastasis, can only be enrolled in the Part 2 study).
- •Patients who have second primary malignant tumors within the past 3 years prior to screening, except for those who have been cured of basal cell carcinoma, cervical carcinoma in situ, or breast carcinoma in situ.
- •Patients with clinically significant cardiovascular or cerebrovascular diseases, including:
- •Uncontrolled hypertension (systolic blood pressure ≥ 160 mmHg and/or diastolic blood pressure ≥ 110 mmHg) despite treatment;
- •History of myocardial infarction or unstable angina pectoris within 6 months prior to the first dose of study drug;
- •History of cerebral hemorrhage, cerebral infarction or transient ischemic attack (TIA) within 6 months prior to the first dose of study drug;
- •Congestive heart failure (left ventricular ejection fraction [LVEF] < 50%);
- •Severe symptomatic arrhythmia requiring medication, except for asymptomatic atrial fibrillation that is controllable;
- •The QT interval corrected for heart rate (QTcF) > 470 msec based on the mean value of triplicate ECG tests, or family history of congenital long QT syndrome.
- •Active uncontrolled infections requiring intravenous antibiotics or hospitalization.
- •Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of DAT-2645 and no history of bowel obstruction within 6 months prior to enrollment.
- •Known pulmonary interstitial disease or pulmonary interstitial fibrosis.
- •Patients known hypersensitivity to any component or excipient of DAT-
- •Any unresolved toxicities from any prior therapy with severity great than CTCAE Grade 1 prior to start of DAT-2645, except for alopecia and pigmentation and Grade 2 of peripheral sensory neuropathy.
- •Participated in other clinical trials (except for screening failure) within 4 weeks prior to the first dose of the study drug in this study.
- •Known active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection (active HBV infection is defined as positive hepatitis B surface antigen [HbsAg], or HBV DNA exceeding the lower limit of detection; active HCV infection is defined as positive anti-HCV antibody, and HCV RNA exceeding the lower limit of detection).
- •Known human immunodeficiency virus (HIV) infection (patients with adequate CD4+ T cell counts and without history of acquired immune deficiency syndrome [AIDS]-defining opportunistic infections could be enrolled after consultation with sponsor).
- •Women who are pregnant or breastfeeding.
- •Patients who have used moderate/strong inhibitors or inducers of CYP3A, P-gp inhibitors and substrates of P-gp, MATE1, MATE2-K with a narrow therapeutic indexes, within 14 days or 5 half-lives of this drug (depends on which is longer) prior to the first dose of DAT-
- •Patients who have used medication known to prolong the QT interval within 14 days prior to the first dose of DAT-
- •Patients who have used acid-suppressing drugs within 3 days or 5 half-lives of this drug (depends on which is longer) prior to the first dose of DAT-
- •History or evidence of any other clinically significant condition or disease (with the exception of those outlined above) that, in the opinion of the investigator, would be a risk to patient safety or interfere with the study evaluation, procedures or completion.
研究组 & 干预措施
Part 1, Dose escalation
Experimental
Monotherapy, dose escalation to definite MTD or RDE.
干预措施: DAT-2645 tablet (Drug)
Module 1 Part 2, Dose optimizing
Experimental
Dose optimizing by 2 dose level after dose escalation to definite RP2D
干预措施: DAT-2645 tablet (Drug)
Module 2 Part 2, Dose expansion
Experimental
To evaluate safety and efficacy of DAT-2645 tablet in solid tumor under RP2D dosage
干预措施: DAT-2645 tablet (Drug)
结局指标
主要结局
Part 1, Dose esclalation study:To characterize the safety and tolerability of DAT-2645 monotherapy by evaluating the number of participants with dose limiting toxicities, adverse events, and laboratory abnormalities as graded by NCI CTCAE version 5.0
时间窗: 6 months
The incidence of dose limiting toxicites Incidence of treatment-emergent Adverse Events as characterized by type, frequency, severity (as graded by NCI CTCAE version 5.0), timing, seriousness, and relationship to study therapy Laboratory abnormalities as characterized by type, frequency, severity (as graded by NCI CTCAE version 5.0), and timing
Part 2, Dose expansion study: To evaluate preliminary preliminary anti-tumor activity of DAT-2645 tablet monotherapy in participants by measuring tumor Overall Response Rate using RECIST criteria v1.1
时间窗: Approximately 2 years
Tumor response: Overall Response Rate(ORR) assessed by the investigators based on RECIST v1.1 criteria
次要结局
- RP2D(Approximately 6 months)
- ORR(Average of 6 months)
- DCR(Average of 6 months)
- DoR(Approximately 1 years)
- PFS(Approximately 2 years)
- OS(Approximately 2 years)
- Area Under the Plasma Concentration Versus Time Curve (AUC) of DAT-2645(Approximately 1 years)
- Changes in lysate poly (ADP-ribose) (PAR) level(6 months)
- Correlations between patients' baseline characteristics and effecacy(Approximately 2 years)
- Time to Achieve Maximal Plasma Concentration (Tmax) of DAT-2645 in Part 1 and Part 2(Approximately 1 years)
- Maximal Plasma Concentration (Cmax) of DAT-2645 in Part 1 and Part 2(Approximately 1 years)
研究者
研究点 (2)
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