2022-502528-29-00招募中2 期
A Phase 1/2 Study to Evaluate the Safety, Pharmacokinetics, and Efficacy of BLU-222 as a Single Agent and in Combination Therapy for Patients with Advanced Solid Tumors
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 50
- 试验地点
- 12
- 主要终点
- Phase 1: • MTD determination: DLT rate; • RP2D determination: DLT, PK, pharmacodynamics, and preliminary safety data. • Overall safety profile of BLU-222, as assessed by the TEAEs, changes in vital signs, ECGs, and clinical laboratory parameters
研究概览
简要总结
Phase 1: • To determine the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) of BLU-222 monotherapy and in combination with carboplatin or ribociclib and fulvestrant. • To evaluate the safety and tolerability of BLU-222 monotherapy and in combination with carboplatin or ribociclib and fulvestrant. Phase 2 : • To assess the anticancer activity of BLU-222 at the RP2D in patients with advanced solid tumors, as a monotherapy and in combination with carboplatin, fulvestrant, or ribociclib and fulvestrant. • To evaluate the safety and tolerability of BLU222 monotherapy and in combination with carboplatin, fulvestrant, or ribociclib and fulvestrant
研究设计
- 分配方式
- Not Applicable
- 主要目的
- (vela) Study Of Blu-222 In Advanced Solid Tumors
- 盲法
- None
入排标准
- 年龄范围
- 18 years 至 65+ years（18-64 Years, 65+ Years）
- 接受健康志愿者
- 是
入选标准
- •Advanced solid tumors that has progressed beyond standard of care OR 2)HR+ HER2- BC that has progressed following treatment with a CDK4/6 inhibitor OR 3)Endometrial and gastric cancer that has progressed after at least 2 prior therapies (including one prior platinum therapy) OR 4)Platinum refractory or platinum resistant ovarian cancer 5)CCNE1 amplified tumors that have progressed beyond standard of care
排除标准
- •Have visceral crisis, lymphangitic spread, or leptomeningeal carcinomatosis.
- •Have active, uncontrolled infection (viral, bacterial, or fungal), including tuberculosis, hepatitis B virus (HBV), hepatitis C virus, AIDSrelated illness, or COVID-19 infection (symptoms and a positive test result).
- •Requires treatment with a prohibited medication or herbal remedy that cannot be discontinued at least 2 weeks before the start of study drug administration.
- •Have planned major surgical procedure within 14 days of the first dose of study drug (procedures such as central venous catheter placement, tumor needle biopsy, and feeding tube placement are not considered major surgical procedures).
- •Unwilling or unable to comply with scheduled visits, study drug administration plan, laboratory tests, or other study procedures and study restrictions.
- •Patient is a woman who is not postmenopausal or surgically sterile, and is unwilling to abstain from sexual intercourse or employ highly effective contraception OR is a man who is not surgically sterile, and is unwilling to abstain from sexual intercourse or employ highly effective contraception
- •Patient is a pregnant female
- •Have received the following anticancer therapy: a. Previous therapy with CDK2i, PKMYT1i, or WEE1i, except in Part 1A where up to 10 patients who previously received PKMYT1i, or WEE1 inhibitor will be permitted.
- •Have central nervous system (CNS) metastases or spinal cord compression that is associated with progressive neurological symptoms or requires increasing doses of corticosteroids to control the CNS disease.
- •Have known intracranial hemorrhage and/or bleeding diatheses.
- •Have clinically active ongoing ILD of any etiology, including drug induced ILD, and radiation pneumonitis within 28 days prior to initiation of study treatment.
- •Have any unresolved toxicities from prior therapy greater than CTCAE Grade 1 or that have not resolved to baseline at the time of starting the study.
- •Have mean resting QTcF > 450 msec, a history of prolonged QT syndrome or Torsades de pointes, or a familial history of prolonged QT syndrome.
- •Have clinically significant, uncontrolled, cardiovascular diseaseincluding congestive heart failure Grade III or IV according to the New York Heart Association classification; myocardial infarction or unstable angina within the previous 6 months, uncontrolled hypertension, or clinically significant, uncontrolled arrhythmias, including bradyarrhythmia that may cause QT prolongation (eg, Type II second degree heart block or thirddegree heart block).
- •Have a history of another primary malignancy other than completely resected carcinomas in situ) that has been diagnosed or required therapy within 2 years prior to initiation of study treatment.
结局指标
主要结局
Phase 1: • MTD determination: DLT rate; • RP2D determination: DLT, PK, pharmacodynamics, and preliminary safety data. • Overall safety profile of BLU-222, as assessed by the TEAEs, changes in vital signs, ECGs, and clinical laboratory parameters
Phase 1: • MTD determination: DLT rate; • RP2D determination: DLT, PK, pharmacodynamics, and preliminary safety data. • Overall safety profile of BLU-222, as assessed by the TEAEs, changes in vital signs, ECGs, and clinical laboratory parameters
Phase 2: • Overall response rate (ORR), defined as the proportion of patients with confirmed CR or PR according to RECIST v1.1; • Overall safety profile of BLU-222, as assessed by the TEAEs, changes in vital signs, ECGs, and clinical laboratory parameters.
Phase 2: • Overall response rate (ORR), defined as the proportion of patients with confirmed CR or PR according to RECIST v1.1; • Overall safety profile of BLU-222, as assessed by the TEAEs, changes in vital signs, ECGs, and clinical laboratory parameters.
次要结局
- Phase 1: 1. ORR, defined in Section 3.1.
- 2. DOR, defined as the time from first documented response of either CR or PR to the date of first documented progressive disease or death due to any cause, whichever occurs first. DOR will be analyzed for patients with confirmed CR or PR.
- 3. DCR, defined as the proportion of patients with confirmed CR, PR, or stable disease according to RECIST v1.1
- 4. CBR, defined as the proportion of patients with confirmed CR, PR, or stable disease which the stable disease has been lasting ≥ 16 weeks from first dose date according to RECIST v1.1
- 5. PFS, defined as the time from the first dose of BLU-222 until the date of first documented progressive disease or death due to any cause, whichever occurs first
- 6. PK parameters of BLU-222 will include, as appropriate, Cmax, Tmax, Tlast, AUC0-24 for QD and AUC0-12 for BID, Ctrough, Vz/F, t½, CL/F, and accumulation ratio
- 7. Correlations between PK parameters and safety findings of interest will be evaluated.
- 8. Correlations between PK parameters and antitumor activity endpoints findings of interest will be evaluated.
- 9. PK parameters of single oral doses of BLU-222 administered with or without a high-fat meal in patients, including Cmax, Tmax, AUC0-last measurements
- 10. PK parameters of single oral doses of BLU-222 administered as the 1st and 2nd generation capsules, including Cmax, Tmax, AUC0-last
- 11. Profile pharmacodynamic changes in the cyclin E/CDK2 pathway biomarker expression levels of phospho-Rb and other markers
- 12. CA-125 response as defined by the GCIG CA-125 response criteria
- Phase 2: 1. DOR, DCR, CBR (as defined for Phase 1 above). PFS, defined as the time from the first dose of BLU-222 until the date of first documented progressive disease or death due to any cause, whichever occurs first OS, defined as the time from the first dose of BLU-222 until the date of death due to any cause
- 2. CA-125 response as defined by GCIG CA-125 response criteria
- 3. PK parameters of BLU-222 will include, as appropriate, Cmax, Clast, Tmax or AUC0-last
- 4. Correlations between PK parameters and safety findings of interest will be evaluated.
- 5. Correlations between PK parameters and antitumor activity endpoints will be evaluated.
研究者
Tanya Green
Scientific
Blueprint Medicines Corp.
研究点 (12)
Loading locations...
相似试验
招募中
2 期
Study of BLU-808 in Chronic Inducible Urticaria and Chronic Spontaneous Urticaria2024-520031-33-00Blueprint Medicines Corp.57
招募中
2 期
Phase 1/2 Study of BLU-451 in certain advanced cancers2022-502527-21-00Blueprint Medicines Corp.28
招募中
1 期
Study of [212Pb]Pb-DOTAM-MAM279 ([212Pb]Pb-MP0712) in Patients With Small Cell Lung Cancer and Other DLL3 Expressing Solid TumorsNCT07278479Molecular Partners AG138
招募中
2 期
Phase I/II study to determine the safety and efficacy of Ribociclib in combination with hormone therapy and hypofractionated radiotherapy in breast cancer, with positive hormone receptors and negative HER2 status, in newly diagnosed, not immediately operable (or wishing to avoid surgery), elderly patientbreast cancer2022-501527-24-00Centre Antoine Lacassagne85
撤回
2 期
Evaluation of the safety and efficacy of the drug AL8326 in the post-first treatment of small cell lung cancer.2023-509067-24-00Advenchen Pharmaceuticals LLC30