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Purpose

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.

Conditions

Eligibility

Eligible Ages
Over 18 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

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

Phase
Phase 1/Phase 2
Study Type
Interventional
Allocation
Non-Randomized
Intervention Model
Sequential Assignment
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
BLU-222 Monotherapy 		Dose Escalation: Multiple doses for BLU-222 for oral administration Dose Expansion: Oral dose of BLU-222 as determined during Dose Escalation
  • Drug: BLU-222
    Oral administration
Experimental
BLU-222 + Carboplatin 		Dose Escalation: Multiple doses for BLU-222 for oral administration at doses deemed appropriate based on BLU-222 Monotherapy arm and multiple doses of Carboplatin at the approved dose. Dose Expansion: Oral dose of BLU-222 as determined during Dose Escalation and Carboplatin IV infusion at approved dose
  • Drug: BLU-222
    Oral administration
  • Drug: Carboplatin
    IV Infusion
Experimental
BLU-222 + Ribociclib + Fulvestrant 		Dose Escalation: Multiple doses for BLU-222 for oral administration at doses deemed appropriate based on BLU-222 Monotherapy arm along with Ribociclib and Fulvestrant at the approved doses. Dose Expansion: Oral dose of BLU-222 as determined during dose escalation and approved doses of Ribociclib and Fulvestrant
  • Drug: BLU-222
    Oral administration
  • Drug: Ribociclib
    Oral administration
  • Drug: Fulvestrant
    Intra muscular administration
Experimental
BLU-222 + Fulvestrant 		Dose Expansion: Oral dose of BLU-222 as determined during Dose Escalation + fulvestrant at the approved dose
  • Drug: BLU-222
    Oral administration
  • Drug: Fulvestrant
    Intra muscular administration

Recruiting Locations

University of Arkansas for Medical Sciences
Little Rock, Arkansas 72205

UCSF Helen Diller Family Comprehensive Cancer Center
San Francisco, California 94158

Stanford Women's Cancer Center
Stanford, California 94305

Florida Cancer Specialists
Sarasota, Florida 34232

University of Chicago Medical Center
Chicago, Illinois 60637

Johns Hopkins Sidney Kimmel Comprehensive Cancer Center (SKCCC)
Baltimore, Maryland 21287

Massachusetts General Hospital
Boston, Massachusetts 02114

Dana-Farber Cancer Institute
Boston, Massachusetts 02215

Henry Ford Health System
Detroit, Michigan 48202

Columbia University Herbert Irving Comprehensive Cancer Center
New York, New York 10032

Memorial Sloan Kettering Cancer Center
New York, New York 10065

Montefiore Medical Center
New York, New York 10461

UNC Hospitals at Chapel Hill - The University of North Carolina at Chapel Hill
Chapel Hill, North Carolina 27514

OU Health Stephenson Cancer Center
Oklahoma City, Oklahoma 73104

Hospital of the Fox Chase Cancer Center
Philadelphia, Pennsylvania 19111

Vanderbilt Breast Center at One Hundred Oaks
Nashville, Tennessee 37204

MD Anderson Cancer Center
Houston, Texas 77030

University of Utah - Huntsman Cancer Institute - PPDS
Salt Lake City, Utah 84112

University of Virginia Comprehensive Cancer Center
Charlottesville, Virginia 22903

More Details

NCT ID
NCT05252416
Status
Recruiting
Sponsor
Blueprint Medicines Corporation

Study Contact

Blueprint Medicines
617-714-6707
medinfo@blueprintmedicines.com

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.