(VELA) Study of BLU-222 in Advanced Solid Tumors
- Conditions
- HR+ Breast CancerCarcinosarcomaAdvanced Solid TumorsCCNE1 AmplificationHER2-negative Breast CancerGastric CancerEsophageal AdenocarcinomaOvarian CancerEndometrial Cancer
- Interventions
- Registration Number
- NCT05252416
- Lead Sponsor
- Blueprint Medicines Corporation
- Brief 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 366
- Advanced solid tumors that has progressed beyond standard of care OR
- HR+ HER2- BC that has progressed following treatment with a CDK4/6 inhibitor OR
- Endometrial and gastric cancer that has progressed after at least 2 prior therapies (including one prior platinum therapy) OR
- Platinum refractory or platinum resistant ovarian cancer CCNE1 amplified tumors that have progressed beyond standard of care
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Have visceral crisis, lymphangitic spread, or leptomeningeal carcinomatosis.
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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.
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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.
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Have known intracranial hemorrhage and/or bleeding diatheses.
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Have clinically active ongoing ILD of any etiology, including drug-induced ILD, and radiation pneumonitis within 28 days prior to initiation of study treatment.
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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.
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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.
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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).
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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.
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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).
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Requires treatment with a prohibited medication or herbal remedy that cannot be discontinued at least 2 weeks before the start of study drug administration.
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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).
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Unwilling or unable to comply with scheduled visits, study drug administration plan, laboratory tests, or other study procedures and study restrictions.
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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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description BLU-222 Monotherapy BLU-222 Dose Escalation: Multiple doses for BLU-222 for oral administration Dose Expansion: Oral dose of BLU-222 as determined during Dose Escalation BLU-222 + Fulvestrant BLU-222 Dose Expansion: Oral dose of BLU-222 as determined during Dose Escalation + fulvestrant at the approved dose BLU-222 + Ribociclib + Fulvestrant Ribociclib 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 BLU-222 + Carboplatin BLU-222 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 BLU-222 + Ribociclib + Fulvestrant BLU-222 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 BLU-222 + Carboplatin 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 BLU-222 + Ribociclib + Fulvestrant 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 BLU-222 + Fulvestrant Fulvestrant Dose Expansion: Oral dose of BLU-222 as determined during Dose Escalation + fulvestrant at the approved dose
- Primary Outcome Measures
Name Time Method [Phase 1] Determine the recommended Phase 2 dose (RP2D) of BLU-222 Approximately 21 months [Phase 1] Determine the maximum tolerated dose (MTD) of BLU-222 Approximately 21 months [Phase 1] Rate and severity of adverse events Approximately 21 months [Phase 2] Overall response rate (ORR) Approximately 43 months [Phase 2] Rate and severity of adverse events Approximately 43 months
- Secondary Outcome Measures
Name Time Method [Phase 1] Apparent volume of distribution (Vz/F) Approximately 21 months [Phase 1] Accumulation ratio (R) Approximately 21 months [Phase 1 and Phase 2] Time to maximum plasma drug concentration (Tmax) Approximately 43 months [Phase 1] Terminal elimination half-life (t½) Approximately 21 months [Phase 1] Overall response rate (ORR) Approximately 21 months [Phase 1 and Phase 2] Duration of Response (DOR) Approximately 43 months [Phase 1 and Phase 2] Clinical benefit rate (CBR) Approximately 43 months [Phase 2] Overall survival (OS) Approximately 43 months [Phase 1 and Phase 2] Change in CA-125 levels Approximately 43 months [Phase 1] Time of last quantifiable plasma drug concentration (Tlast) Approximately 21 months [Phase 1] Area under the plasma concentration time curve from time 0 to 12 hours (AUC0-12) Approximately 21 months [Phase 1] To assess treatment-induced modulation of biomarkers Approximately 21 months [Phase 1 and Phase 2] Disease control rate (DCR) Approximately 43 months [Phase 1 and Phase 2] Last measurable concentration (Clast) Approximately 43 months [Phase 1 and Phase 2] Maximum plasma drug concentration (Cmax) Approximately 43 months [Phase 1] Area under the plasma concentration time curve from time 0 to 24 hours (AUC0-24) Approximately 21 months [Phase 1] Trough concentration (Ctrough) Approximately 21 months [Phase 1] Apparent oral clearance(CL/F) Approximately 21 months [Phase 1 and Phase 2] Progression free survival (PFS) Approximately 43 months [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
Trial Locations
- Locations (23)
University of Arkansas for Medical Sciences
đŸ‡ºđŸ‡¸Little Rock, Arkansas, United States
UCSF Helen Diller Family Comprehensive Cancer Center
đŸ‡ºđŸ‡¸San Francisco, California, United States
Stanford Women's Cancer Center
đŸ‡ºđŸ‡¸Stanford, California, United States
Florida Cancer Specialists
đŸ‡ºđŸ‡¸Sarasota, Florida, United States
University of Chicago Medical Center
đŸ‡ºđŸ‡¸Chicago, Illinois, United States
Johns Hopkins Sidney Kimmel Comprehensive Cancer Center (SKCCC)
đŸ‡ºđŸ‡¸Baltimore, Maryland, United States
Massachusetts General Hospital
đŸ‡ºđŸ‡¸Boston, Massachusetts, United States
Dana-Farber Cancer Institute
đŸ‡ºđŸ‡¸Boston, Massachusetts, United States
Henry Ford Health System
đŸ‡ºđŸ‡¸Detroit, Michigan, United States
Columbia University Herbert Irving Comprehensive Cancer Center
đŸ‡ºđŸ‡¸New York, New York, United States
Memorial Sloan Kettering Cancer Center
đŸ‡ºđŸ‡¸New York, New York, United States
Montefiore Medical Center
đŸ‡ºđŸ‡¸New York, New York, United States
UNC Hospitals at Chapel Hill - The University of North Carolina at Chapel Hill
đŸ‡ºđŸ‡¸Chapel Hill, North Carolina, United States
OU Health Stephenson Cancer Center
đŸ‡ºđŸ‡¸Oklahoma City, Oklahoma, United States
Hospital of the Fox Chase Cancer Center
đŸ‡ºđŸ‡¸Philadelphia, Pennsylvania, United States
Vanderbilt Breast Center at One Hundred Oaks
đŸ‡ºđŸ‡¸Nashville, Tennessee, United States
MD Anderson Cancer Center
đŸ‡ºđŸ‡¸Houston, Texas, United States
University of Utah - Huntsman Cancer Institute - PPDS
đŸ‡ºđŸ‡¸Salt Lake City, Utah, United States
University of Virginia Comprehensive Cancer Center
đŸ‡ºđŸ‡¸Charlottesville, Virginia, United States
Fondazione IRCCS Istituto Nazionale dei Tumori
đŸ‡®đŸ‡¹Milano, Italy
Instituto Europeo di Oncologia
đŸ‡®đŸ‡¹Milano, Italy
Fondazione Policlinico Universitario A Gemelli-Rome
đŸ‡®đŸ‡¹Rome, Italy
St Bartholomew's Hospital
đŸ‡¬đŸ‡§London, Middlesex, United Kingdom