Ovarian Cancer Clinical Trial
Official title:
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
This is a Phase 1/2, open-label, first-in-human (FIH) study designed to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and anticancer activity of BLU-222, a selective inhibitor of CDK2.
Status | Recruiting |
Enrollment | 366 |
Est. completion date | September 30, 2026 |
Est. primary completion date | November 30, 2025 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years and older |
Eligibility | Inclusion Criteria: 1. 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 CCNE1 amplified tumors that have progressed beyond standard of care Exclusion Criteria: 1. Have visceral crisis, lymphangitic spread, or leptomeningeal carcinomatosis. 2. 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. 3. 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. 4. Have known intracranial hemorrhage and/or bleeding diatheses. 5. Have clinically active ongoing ILD of any etiology, including drug-induced ILD, and radiation pneumonitis within 28 days prior to initiation of study treatment. 6. 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. 7. Have mean resting QTcF > 450 msec in men or QTcF > 470 msec in women, a history of prolonged QT syndrome or Torsades de pointes, or a familial history of prolonged QT syndrome. 8. Have clinically significant, uncontrolled, cardiovascular disease including 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 third-degree heart block). 9. 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. 10. Have known active, uncontrolled infection (viral, bacterial, or fungal), including tuberculosis, hepatitis B virus (HBV), hepatitis C virus, AIDS-related illness, or COVID-19 infection (symptoms and a positive test result). 11. Requires treatment with a prohibited medication or herbal remedy that cannot be discontinued at least 2 weeks before the start of study drug administration. 12. 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). 13. Unwilling or unable to comply with scheduled visits, study drug administration plan, laboratory tests, or other study procedures and study restrictions. 14. 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 15. Patient is a pregnant female |
Country | Name | City | State |
---|---|---|---|
Italy | Fondazione IRCCS Istituto Nazionale dei Tumori | Milano | |
Italy | Instituto Europeo di Oncologia | Milano | |
Italy | Fondazione Policlinico Universitario A Gemelli-Rome | Rome | |
United Kingdom | St Bartholomew's Hospital | London | Middlesex |
United States | Johns Hopkins Sidney Kimmel Comprehensive Cancer Center (SKCCC) | Baltimore | Maryland |
United States | Dana-Farber Cancer Institute | Boston | Massachusetts |
United States | Massachusetts General Hospital | Boston | Massachusetts |
United States | UNC Hospitals at Chapel Hill - The University of North Carolina at Chapel Hill | Chapel Hill | North Carolina |
United States | University of Virginia Comprehensive Cancer Center | Charlottesville | Virginia |
United States | University of Chicago Medical Center | Chicago | Illinois |
United States | Henry Ford Health System | Detroit | Michigan |
United States | MD Anderson Cancer Center | Houston | Texas |
United States | University of Arkansas for Medical Sciences | Little Rock | Arkansas |
United States | Vanderbilt Breast Center at One Hundred Oaks | Nashville | Tennessee |
United States | Columbia University Herbert Irving Comprehensive Cancer Center | New York | New York |
United States | Memorial Sloan Kettering Cancer Center | New York | New York |
United States | Montefiore Medical Center | New York | New York |
United States | OU Health Stephenson Cancer Center | Oklahoma City | Oklahoma |
United States | Hospital of the Fox Chase Cancer Center | Philadelphia | Pennsylvania |
United States | University of Utah - Huntsman Cancer Institute - PPDS | Salt Lake City | Utah |
United States | UCSF Helen Diller Family Comprehensive Cancer Center | San Francisco | California |
United States | Florida Cancer Specialists | Sarasota | Florida |
United States | Stanford Women's Cancer Center | Stanford | California |
Lead Sponsor | Collaborator |
---|---|
Blueprint Medicines Corporation |
United States, Italy, United Kingdom,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | [Phase 1] Determine the maximum tolerated dose (MTD) of BLU-222 | Approximately 21 months | ||
Primary | [Phase 1] Determine the recommended Phase 2 dose (RP2D) of BLU-222 | Approximately 21 months | ||
Primary | [Phase 1] Rate and severity of adverse events | Approximately 21 months | ||
Primary | [Phase 2] Overall response rate (ORR) | Approximately 43 months | ||
Primary | [Phase 2] Rate and severity of adverse events | Approximately 43 months | ||
Secondary | [Phase 1] Overall response rate (ORR) | Approximately 21 months | ||
Secondary | [Phase 1] Time of last quantifiable plasma drug concentration (Tlast) | Approximately 21 months | ||
Secondary | [Phase 1] Area under the plasma concentration time curve from time 0 to 12 hours (AUC0-12) | Approximately 21 months | ||
Secondary | [Phase 1] Area under the plasma concentration time curve from time 0 to 24 hours (AUC0-24) | Approximately 21 months | ||
Secondary | [Phase 1] Trough concentration (Ctrough) | Approximately 21 months | ||
Secondary | [Phase 1] Apparent volume of distribution (Vz/F) | Approximately 21 months | ||
Secondary | [Phase 1] Terminal elimination half-life (t½) | Approximately 21 months | ||
Secondary | [Phase 1] Apparent oral clearance(CL/F) | Approximately 21 months | ||
Secondary | [Phase 1] Accumulation ratio (R) | Approximately 21 months | ||
Secondary | [Phase 1] To assess treatment-induced modulation of biomarkers | Approximately 21 months | ||
Secondary | [Phase 1 and Phase 2] Duration of Response (DOR) | Approximately 43 months | ||
Secondary | [Phase 1 and Phase 2] Disease control rate (DCR) | Approximately 43 months | ||
Secondary | [Phase 1 and Phase 2] Clinical benefit rate (CBR) | Approximately 43 months | ||
Secondary | [Phase 1 and Phase 2] Progression free survival (PFS) | Approximately 43 months | ||
Secondary | [Phase 1 and Phase 2] Change in CA-125 levels | Approximately 43 months | ||
Secondary | [Phase 1 and Phase 2] Maximum plasma drug concentration (Cmax) | Approximately 43 months | ||
Secondary | [Phase 1 and Phase 2] Time to maximum plasma drug concentration (Tmax) | Approximately 43 months | ||
Secondary | [Phase 1 and Phase 2] Last measurable concentration (Clast) | Approximately 43 months | ||
Secondary | [Phase 1 and Phase 2] Area under the concentration-time curve from time 0 to the time of the last measured concentration AUC(0-last) | Approximately 43 months | ||
Secondary | [Phase 2] Overall survival (OS) | Approximately 43 months |
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