NCT04395677进行中（未招募）2 期
A Multicenter, Open Label, Single Arm Phase 2 Study of AB-106 in the Treatment of Locally Advanced and Metastatic NSCLC
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 173
- 试验地点
- 1
- 主要终点
- Best overall response (BOR) by IRC
研究概览
简要总结
The purpose of the study is to evaluate safety, pharmacokinetics and efficacy of AB-106 monotherapy in the treatment of advanced NSCLC.
详细描述
This is a Phase II, multicenter, single-arm, open label study of AB-106 in the Chinese patients with advanced NSCLC harboring ROS1 fusion gene.The study will be divided into two stages. First stage (Stage I) is to determine the clinical optimal dose of AB-106, which will be evaluated at two dose levels (400 mg QD and 600mg QD), and the safety, tolerability and pharmacokinetics of AB-106 will be evaluated at the same time; Second stage (Stage II) is to evaluate the efficacy and safety of AB-106 at the clinical optimal dose determined from Stage I. It is expected that 6 patients with advanced NSCLC harboring ROS1 fusion will be enrolled in the first stage. About 167 patients with ROS1 fusion will be enrolled in the second stage and divided into two treatment cohorts (Cohort A & Cohort B). It is planned to enroll about 106 ROS1-TKI treatment naïve patients in Cohort A and about 67 crizotinib pre-treated patients in Cohort B. AB-106 will be administered 600mg once daily in 21-day cycles. Patients will continue with the study treatment until progression of disease as determined by the investigator. The frequency of tumor assessments is once every 2 treatment cycles through Cycle 9, then every 3 treatment cycles through Cycle 27 and every 4 treatment cycles thereafter.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 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 must meet all of the following criteria to be eligible for enrollment into the study:
- •≥ 18 years of age
- •Histologically or cytologically confirmed locally advanced or metastatic NSCLC
- •Positivity of ROS1 fusion is determined by the local qualified laboratories by using the FISH, RT-PCR or NGS assay, and the subject must provide archival tumor tissue sample for the confirmation by a sponsor-designated central laboratory
- •The subject is either TKI treatment naïve(Cohort A)， or has disease progression following the treatment of crizotinib （Cohort B）
- •The patient with brain metastases is either asymptomatic, or neurologically stable for at least 2 weeks prior to study entry
- •Prior therapies (including chemotherapies [less than 3 lines of regimen], radiotherapy [except for palliative], or surgery) should be completed at least 2 weeks prior to study entry. The palliative radiotherapy (≤10 times) should be completed within 48 hours prior to study entry. Any acute toxic effect must be resolved to CTCAE Grade ≤1 except for alopecia
- •At least one measurable target tumor lesion (as accessed by RECIST v1.1) that has not been irradiated
- •ECOG Performance Status: 0 or 1
- •Patient with a life expectancy ≥ 3 months based on the judgement of investigators
- •Adequate organ functions defined by the following criteria：
- •Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT) ≤2.5 x ULN; or ≤5 x ULN， if there is liver metastases involvement；
- •Total serum bilirubin ≤1.5 x ULN；
- •Absolute neutrophil count（ANC） ≥1500/µL；
- •Platelet count≥100,000/µL；
- •Hemoglobin≥8.0 g/dL；
- •Serum creatinine ≤2 x ULN.
- •Evidence of a personally signed and dated informed consent document indicating that the patient has been informed of the pertinent aspect of the study
- •Willingness and ability to comply with the study scheduled visits, treatment plans, laboratory tests and other procedures
- •Male and female patients of childbearing potential must agree to sue effective methods of contraception throughout the study and for 90 days after the last dose of study medication.
排除标准
- •Patient presenting with any of the following criteria will not be included in the study：
- •Current participation in other therapeutic investigational studies
- •Previous participation in the treatment or clinical trials of other ROS1-TKIs (except for crizotinib)
- •Previous participation in the treatment and clinical trials of ALK or NTRK fusion gene targeted therapies.
- •Spinal cord compression unless the patient demonstrates good pain control and stabilization or recovery of neurological function, carcinomatous meningitis or leptomeningeal disease
- •Patients with interstitial fibrosis or interstitial lung disease
- •Any one of the following currently or in the previous 3 months: myocardial infarction, severe/unstable angina, coronary/ peripheral artery bypass graft, congestive heart failure or cerebrovascular accident including transient ischemic attack
- •Ongoing cardiac dysrhythmias of NCI CTCAE (v5.0) Grade≥2, uncontrolled atrial fibrillation of any grade, or QTc interval>470 microsec
- •Pregnancy or breastfeeding
- •Current use of food or drugs that are known strong CYP3A inhibitors, including (but not limited to) atazanavir, clarithromycin, indinavir, itraconazole, ketoconazole, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, troleandomycin, voriconazole, grapefruit or grapefruit juice.
- •Current use of drugs that are known strong CYP3A4 inducers, including (but not limited to) carbamazepine, phenobarbital, phenytoin, rifabutin, rifampin, and St John's Wort
- •Current use of drugs that are known CYP3A4 substrates with narrow therapeutic indices, including (but not limited to) dihydroergotamine, ergotamine, pimozide, astemizole, cisapride, and terfenadine.
- •Current use of drugs that are known to induce QTc prolongation
- •Systematic treatment with anti-cancer therapy, including any Traditional Chinese Medicine (TCM)with anti-tumor effect indicated in the prescription information.
- •Evidence of active malignancy (other than current NSCLC, non-melanoma skin cancer, in situ cervical cancer, and presumed cured prostate cancer) within the last 3 years
- •Clinically active viral disease with positivity of serum HIV, HBV, HCV, RPR testing
- •Difficult to swallow which may significantly impact drug absorption
- •Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation in the judgement of investigator and sponsor
研究组 & 干预措施
AB-106 （DS-6051b）
Experimental
Single-arm trial whereby all consented, enrolled, eligible patients receive AB-106
干预措施: AB-106 (Drug)
结局指标
主要结局
Best overall response (BOR) by IRC
时间窗: 6 months
Best overall response (BOR) based on independent radiology review by Independent Review Committee(IRC) according to RECIST 1.1
次要结局
- Number of participants with treatment-related adverse events as assessed by CTCAE v5.0(25 months)
- Rate of ECG QT Interval prolongation patients in all patients(25 months)
- Trough plasma concentration [Ctrough](Day 1 to Cycle1Day15)
- Time to reach maximum plasma concentration [Tmax](Day 1 to Cycle1Day15)
- Duration of intracranial response (IDOR)(25 months)
- Maximum Plasma Concentration [Cmax](Day 1 to Cycle1Day15)
- Progression free Survival(PFS)(25 months)
- Average plasma concentration at steady state over dosing interval [Cav](Day 1 to Cycle1Day15)
- Time to Response(TTR)(6 months)
- Overall Survival(OS)(51 months)
- Area under the curve from time zero to τ (dose interval τ is 24 h in this study) [AUCτ](Day 1 to Cycle1Day15)
- Duration of Response(DOR)(25 months)
- Intracranial best overall response (IBOR)(25 months)
- Time to Progress(TTP)(25 months)
研究者
研究点 (1)
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相关资讯
Taletrectinib Shows Consistent Efficacy Across ROS1+ NSCLC Subgroups Regardless of Prior Chemotherapy or Fusion Partner- Nuvation Bio presented new subgroup analyses from the pivotal TRUST-I and TRUST-II studies at the IASLC 2026 World Conference on Lung Cancer in Seoul.
- In TKI-naive patients, objective response rates were 90.0% with prior chemotherapy versus 89.8% without, with median durations of response of 48.3 and 54.3 months.
- Efficacy was also consistent by ROS1 fusion partner, with ORRs of 89.5% for CD74 fusions and 88.9% for non-CD74 fusions in TKI-naive patients.
- Long-term follow-up showed no new safety signals, with mostly low-grade AST/ALT increases, diarrhea, nausea and vomiting as the most common adverse events.14 hours agoInnovent's Taletrectinib (DOVBLERON®) Receives Expanded Approval in China for ROS1-Positive NSCLC- China's NMPA has approved Innovent's taletrectinib for adults with locally advanced or metastatic ROS1-positive non-small cell lung cancer (NSCLC).
- The approval was based on positive outcomes from the Phase II TRUST-I trial, which showed high and durable overall responses.
- In TKI-naïve patients, taletrectinib achieved a confirmed objective response rate of 91% and intracranial cORR of 88%.
- Taletrectinib is now approved for both first-line and previously treated ROS1-positive NSCLC patients in China.last yearTaletrectinib Approved in China for ROS1-Positive NSCLC, Showing Promise in TKI-Pretreated and Naive Patients• China's NMPA has approved taletrectinib for treating adults with locally advanced or metastatic ROS1-positive NSCLC previously treated with ROS1 TKIs.
• The approval was based on the phase 2 TRUST-I trial, which demonstrated a 51.5% ORR in patients pretreated with crizotinib, with a median DOR of 10.6 months.
• Taletrectinib has also received priority review for first-line treatment of ROS1-positive NSCLC, supported by data showing a 90.6% ORR in TKI-naive patients.
• Clinical trials show taletrectinib's efficacy in CNS penetration and activity against resistance mutations, offering a potential best-in-class safety profile.last year