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Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT05252416
Other study ID # BLU-222-1101
Secondary ID
Status Recruiting
Phase Phase 1/Phase 2
First received
Last updated
Start date April 7, 2022
Est. completion date September 30, 2026

Study information

Verified date April 2024
Source Blueprint Medicines Corporation
Contact Blueprint Medicines
Phone 617-714-6707
Email medinfo@blueprintmedicines.com
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

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.


Recruitment information / eligibility

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

Study Design


Intervention

Drug:
BLU-222
Oral administration
Carboplatin
IV Infusion
Ribociclib
Oral administration
Fulvestrant
Intra muscular administration

Locations

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

Sponsors (1)

Lead Sponsor Collaborator
Blueprint Medicines Corporation

Countries where clinical trial is conducted

United States,  Italy,  United Kingdom, 

Outcome

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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