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(VELA) Study of BLU-222 in Advanced Solid Tumors

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ClinicalTrials.gov Identifier: NCT05252416
Recruitment Status : Recruiting
First Posted : February 23, 2022
Last Update Posted : April 23, 2024
Sponsor:
Information provided by (Responsible Party):
Blueprint Medicines Corporation

Tracking Information
First Submitted Date  ICMJE January 25, 2022
First Posted Date  ICMJE February 23, 2022
Last Update Posted Date April 23, 2024
Actual Study Start Date  ICMJE April 7, 2022
Estimated Primary Completion Date November 30, 2025   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 3, 2023)
  • [Phase 1] Determine the maximum tolerated dose (MTD) of BLU-222 [ Time Frame: Approximately 21 months ]
  • [Phase 1] Determine the recommended Phase 2 dose (RP2D) of BLU-222 [ Time Frame: Approximately 21 months ]
  • [Phase 1] Rate and severity of adverse events [ Time Frame: Approximately 21 months ]
  • [Phase 2] Overall response rate (ORR) [ Time Frame: Approximately 43 months ]
  • [Phase 2] Rate and severity of adverse events [ Time Frame: Approximately 43 months ]
Original Primary Outcome Measures  ICMJE
 (submitted: February 11, 2022)
  • [Phase 1] Determine the maximum tolerated dose (MTD) of BLU-222 [ Time Frame: Up to 18 months ]
  • [Phase 1] Determine the recommended Phase 2 dose (RP2D) of BLU-222 [ Time Frame: Up to 18 months ]
  • [Phase 1] Rate and severity of adverse events [ Time Frame: Up to 18 months ]
  • [Phase 2] Overall response rate (ORR) [ Time Frame: Up to 30 months ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: April 3, 2023)
  • [Phase 1] Overall response rate (ORR) [ Time Frame: Approximately 21 months ]
  • [Phase 1] Time of last quantifiable plasma drug concentration (Tlast) [ Time Frame: Approximately 21 months ]
  • [Phase 1] Area under the plasma concentration time curve from time 0 to 12 hours (AUC0-12) [ Time Frame: Approximately 21 months ]
  • [Phase 1] Area under the plasma concentration time curve from time 0 to 24 hours (AUC0-24) [ Time Frame: Approximately 21 months ]
  • [Phase 1] Trough concentration (Ctrough) [ Time Frame: Approximately 21 months ]
  • [Phase 1] Apparent volume of distribution (Vz/F) [ Time Frame: Approximately 21 months ]
  • [Phase 1] Terminal elimination half-life (t½) [ Time Frame: Approximately 21 months ]
  • [Phase 1] Apparent oral clearance(CL/F) [ Time Frame: Approximately 21 months ]
  • [Phase 1] Accumulation ratio (R) [ Time Frame: Approximately 21 months ]
  • [Phase 1] To assess treatment-induced modulation of biomarkers [ Time Frame: Approximately 21 months ]
  • [Phase 1 and Phase 2] Duration of Response (DOR) [ Time Frame: Approximately 43 months ]
  • [Phase 1 and Phase 2] Disease control rate (DCR) [ Time Frame: Approximately 43 months ]
  • [Phase 1 and Phase 2] Clinical benefit rate (CBR) [ Time Frame: Approximately 43 months ]
  • [Phase 1 and Phase 2] Progression free survival (PFS) [ Time Frame: Approximately 43 months ]
  • [Phase 1 and Phase 2] Change in CA-125 levels [ Time Frame: Approximately 43 months ]
  • [Phase 1 and Phase 2] Maximum plasma drug concentration (Cmax) [ Time Frame: Approximately 43 months ]
  • [Phase 1 and Phase 2] Time to maximum plasma drug concentration (Tmax) [ Time Frame: Approximately 43 months ]
  • [Phase 1 and Phase 2] Last measurable concentration (Clast) [ Time Frame: 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) [ Time Frame: Approximately 43 months ]
  • [Phase 2] Overall survival (OS) [ Time Frame: Approximately 43 months ]
Original Secondary Outcome Measures  ICMJE
 (submitted: February 11, 2022)
  • [Phase 1] Overall response rate (ORR) [ Time Frame: Up to 18 months ]
  • [Phase 1] To assess treatment-induced modulation of cyclin E/CDK2 pathway biomarkers [ Time Frame: Up to 18 months ]
    Retinoblastoma protein (RB1)
  • [Phase 1 and Phase 2] Duration of Response (DOR) [ Time Frame: Up to 43 months ]
  • [Phase 1 and Phase 2] Maximum plasma drug concentration (Cmax) [ Time Frame: Up to 43 months ]
  • [Phase 1 and Phase 2] Time to maximum plasma drug concentration (Tmax) [ Time Frame: Up to 43 months ]
  • [Phase 1 and Phase 2] Time of last quantifiable plasma drug concentration (Tlast) [ Time Frame: Up to 43 months ]
  • [Phase 1 and Phase 2] Area under the plasma concentration versus time curve from time 0 to the end of the dosing interval (AUC0-24) [ Time Frame: Up to 43 months ]
  • [Phase 1 and Phase 2] Trough concentration (Ctrough) [ Time Frame: Up to 43 months ]
  • [Phase 1 and Phase 2] Apparent volume of distribution (Vz/F) [ Time Frame: Up to 43 months ]
  • [Phase 1 and Phase 2] Terminal elimination half-life (t½) [ Time Frame: Up to 43 months ]
  • [Phase 1 and Phase 2] Apparent oral clearance(CL/F) [ Time Frame: Up to 43 months ]
  • [Phase 1 and Phase 2] Accumulation ratio (R) [ Time Frame: Up to 43 months ]
  • [Phase 1 and Phase 2] Change in CA-125 levels [ Time Frame: Up to 43 months ]
  • [Phase 1 and Phase 2] Disease control rate (DCR) [ Time Frame: Up to 43 months ]
  • [Phase 1 and Phase 2] Clinical benefit rate (CBR) [ Time Frame: Up to 43 months ]
  • [Phase 2] Progression free survival (PFS) [ Time Frame: Up to 43 months ]
  • [Phase 2] Overall survival (OS) [ Time Frame: Up to 43 months ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE (VELA) Study of BLU-222 in Advanced Solid Tumors
Official Title  ICMJE 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
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 Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Advanced Solid Tumors
  • HR+ Breast Cancer
  • CCNE1 Amplification
  • HER2-negative Breast Cancer
  • Ovarian Cancer
  • Endometrial Cancer
  • Gastric Cancer
  • Esophageal Adenocarcinoma
  • Carcinosarcoma
Intervention  ICMJE
  • Drug: BLU-222
    Oral administration
  • Drug: Carboplatin
    IV Infusion
  • Drug: Ribociclib
    Oral administration
  • Drug: Fulvestrant
    Intra muscular administration
Study Arms  ICMJE
  • 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
    Intervention: Drug: BLU-222
  • 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

    Interventions:
    • Drug: BLU-222
    • Drug: Carboplatin
  • 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

    Interventions:
    • Drug: BLU-222
    • Drug: Ribociclib
    • Drug: Fulvestrant
  • Experimental: BLU-222 + Fulvestrant
    Dose Expansion: Oral dose of BLU-222 as determined during Dose Escalation + fulvestrant at the approved dose
    Interventions:
    • Drug: BLU-222
    • Drug: Fulvestrant
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: February 11, 2022)		 366
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE September 30, 2026
Estimated Primary Completion Date November 30, 2025   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Blueprint Medicines 617-714-6707 medinfo@blueprintmedicines.com
Listed Location Countries  ICMJE Italy,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT05252416
Other Study ID Numbers  ICMJE BLU-222-1101
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Current Responsible Party Blueprint Medicines Corporation
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Blueprint Medicines Corporation
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Blueprint Medicines Corporation
Verification Date April 2024

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP