A Phase II, Open-label, Multi-center, Basket Study of the ATR Kinase Inhibitor ART0380 Administered Orally as Monotherapy to Patients With Biologically Selected Advanced or Metastatic Solid Tumors (ARTIST)
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 36
- 试验地点
- 15
- 主要终点
- Objective Response Rate (ORR)
研究概览
简要总结
This interventional study will evaluate the efficacy and safety of ART0380 as monotherapy in patients whose tumors have a biology to predict for sensitivity to inhibition of Ataxia-Telangiectasia Mutated and Rad3-related protein kinase (ATR).
详细描述
ART0380 is being developed as an oral anti-cancer agent for the treatment of patients with cancers that have defects in deoxyribonucleic acid (DNA) repair.
The study will recruit selected patients with advanced or metastatic solid tumors, specifically:
- Patients with persistent or recurrent endometrial cancer (EC)
- Patients with advanced or metastatic solid tumors of any histology
Above patients will be randomized in a 1:1 ratio to one of two dose regimens of ART0380.
Safety will be evaluated on a quarterly basis, at a minimum. Patients may continue to receive ART0380 as long as they are continuing to derive benefit from treatment or until disease progression, withdrawal of consent, or until they experience unacceptable drug-related toxicity.
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
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 who have discontinued all previous treatments for cancer for at least 21 days or 5 half-lives (not including palliative radiotherapy at focal sites), whichever is shorter. Palliative radiotherapy must have completed 1 week prior to start of study treatment.
- •Resolution of all toxicities of prior therapy or surgical procedures to baseline or Grade 1 (except for hypothyroidism requiring medication, neuropathy, and alopecia, which must have resolved to Grade ≤2).
- •Have adequate organ function.
- •Patients of childbearing potential and patients with partners of childbearing potential are required to use highly effective contraception.
- •Have an estimated life expectancy of ≥12 weeks, in the judgment of the investigator.
- •Performance status of 0-1 on the Eastern Cooperative Oncology Group scale.
- •Have a non-irradiated tumor tissue sample (archival or newly obtained core biopsy of a tumor lesion) available.
- •Inclusion Criteria specific to each Arm
- •Inclusion Criteria for Arm 1 [ART0380 monotherapy (endometrial cancer patients)]
- •Persistent or recurrent EC with biological selection.
- •Patients should have received taxane/platinum chemotherapy unless contraindicated.
- •Measurable disease.
- •Inclusion Criteria for Arm 2 [ART0380 monotherapy (solid tumors patients)]
- •Advanced or metastatic solid cancers of any histology with biological selection.
- •If a Programmed cell death protein-1 /Programmed death-ligand-1 inhibitor (e.g., pembrolizumab) is approved and available for the patient's cancer, the patient should have received such treatment before participating in this study.
- •Radiologically evaluable disease.
排除标准
- •Patients who are pregnant.
- •Prior treatment with an inhibitor of ATR, WEE1, checkpoint kinase 1 or PKMYT
- •Have a serious concomitant systemic disorder that would compromise the patient's ability to adhere to the protocol.
- •Have ongoing interstitial lung disease or pneumonitis (whether symptomatic or asymptomatic).
- •Patients with treated brain metastases are eligible if follow-up brain imaging after central nervous system (CNS) directed therapy shows no evidence of progression.
- •Have any major gastrointestinal issues that could impact absorption of ART
- •Have a history of allergy or hypersensitivity to study drug components.
- •Have a significant bleeding disorder or vasculitis or had a Grade ≥3 bleeding episode within 12 weeks prior to enrollment.
- •Patients who plan to father a child while in the study or within 16 weeks (5 months in France) after the last administration of study treatment.
研究组 & 干预措施
Arm 2 [ART0380 monotherapy (solid tumors patients)]
Patients with advanced or metastatic solid tumors will receive ART0380 monotherapy in one of two dose regimens for a 21-day cycle.
干预措施: ART0380 (Drug)
Arm 1 [ART0380 monotherapy (endometrial cancer patients)]
Patients with persistent or recurrent endometrial cancer (EC) will receive ART0380 monotherapy in one of two dose regimens for a 21-day cycle.
干预措施: ART0380 (Drug)
结局指标
主要结局
Objective Response Rate (ORR)
时间窗: Until disease progression (Every 6 weeks from randomization Upto 2 Years)
Objective Response Rate (ORR) is defined as the proportion of patients with a complete response (CR) or partial response (PR) to treatment according to Response evaluation criteria in solid tumors (RECIST v1.1).
次要结局
- Best overall response (BOR)(Screening (≤28 days) Until disease progression (Every 6 weeks from randomization Upto 2 Years))
- Overall survival (OS)(Screening (≤28 days) Until overall survival follow-up (Every 12 weeks until data cut-off))
- Number of patients with adverse events(From Cycle 1 (each Cycle is 21-day) Day 1 until 30-day follow-up visit (Upto 2 Years))
- Progression free survival (PFS)(Screening (≤28 days) Until disease progression (Every 6 weeks from randomization Upto 2 Years))
- Maximum plasma concentration (Cmax)(Pre-dose Cycle 1 day 1, 2, 15, 16, 17, 18, Cycle 2 day 1, Cycle 3 day 1 Upto 2 Years (Each Cycle is 21-days))
- Duration of response (DOR)(Screening (≤28 days) Until disease progression or death (Every 6 weeks from randomization Upto 2 Years))
- Change in tumor size(Screening (≤28 days) Until disease progression (Every 6 weeks from randomization Upto 2 Years))
- Disease control rate (DCR)(Screening (≤28 days) Until disease progression (Every 6 weeks from randomization Upto 2 Years))
- Half life (t1/2)(Pre-dose Cycle 1 days 1, 2, 15, 16, 17, 18, Cycle 2 day 1, Cycle 3 day 1 Upto 2 Years (Each Cycle is 21-days))
- Area under the plasma concentration-time curve from zero to infinity (AUC0-inf)(Pre-dose Cycle 1 days 1, 2, 15, 16, 17, 18, Cycle 2 day 1, Cycle 3 day 1 Upto 2 Years (Each Cycle is 21-days))