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Advanced Solid TumorsPhase 1NCT05252416

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

A Phase 1 study testing BLU-222, Carboplatin and Ribociclib in people with Advanced Solid Tumors and HR+ Breast Cancer, run by Blueprint Medicines Corporation at 23 sites in 3 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
BLU-222, Carboplatin and Ribociclib
Could I receive a placebo?
No, everyone receives an active treatment
How many people
50 participants
Where
23 sitesin 3 countries
Study dates
7 Apr 2022to 4 Jul 2025
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • Have visceral crisis, lymphangitic spread, or leptomeningeal carcinomatosis.
  • Have received the following anticancer therapy:
  • 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.
  • 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.
  • Have known intracranial hemorrhage and/or bleeding diatheses.
  • Have clinically active ongoing ILD of any etiology, including drug-induced ILD, and radiation pneumonitis within 28 days prior to initiation of study treatment.
Show all 16Show fewer
  • 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.
  • 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.
  • 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).
  • 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.
  • 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).
  • Requires treatment with a prohibited medication or herbal remedy that cannot be discontinued at least 2 weeks before the start of study drug administration.
  • 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).
  • Unwilling or unable to comply with scheduled visits, study drug administration plan, laboratory tests, or other study procedures and study restrictions.
  • 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

Trial locations and contacts

23 sites in 3 countries.

23 sites in 3 countries

United States19 sites

  • Johns Hopkins Sidney Kimmel Comprehensive Cancer Center (SKCCC)

    Baltimore, Maryland, 21287

  • Massachusetts General Hospital

    Boston, Massachusetts, 02114

  • Dana-Farber Cancer Institute

    Boston, Massachusetts, 02215

  • UNC Hospitals at Chapel Hill - The University of North Carolina at Chapel Hill

    Chapel Hill, North Carolina, 27514

  • University of Virginia Comprehensive Cancer Center

    Charlottesville, Virginia, 22903

  • University of Chicago Medical Center

    Chicago, Illinois, 60637

  • Henry Ford Health System

    Detroit, Michigan, 48202

  • MD Anderson Cancer Center

    Houston, Texas, 77030

  • University of Arkansas for Medical Sciences

    Little Rock, Arkansas, 72205

  • Vanderbilt Breast Center at One Hundred Oaks

    Nashville, Tennessee, 37204

  • 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

  • OU Health Stephenson Cancer Center

    Oklahoma City, Oklahoma, 73104

  • Hospital of the Fox Chase Cancer Center

    Philadelphia, Pennsylvania, 19111

  • University of Utah - Huntsman Cancer Institute - PPDS

    Salt Lake City, Utah, 84112

  • UCSF Helen Diller Family Comprehensive Cancer Center

    San Francisco, California, 94158

  • Florida Cancer Specialists

    Sarasota, Florida, 34232

  • Stanford Women's Cancer Center

    Stanford, California, 94305

Other trials in United States

Italy3 sites

  • Fondazione IRCCS Istituto Nazionale dei Tumori

    Milan, 20133

  • Instituto Europeo di Oncologia

    Milan, 20141

  • Fondazione Policlinico Universitario A Gemelli-Rome

    Rome, 00168

Other trials in Italy

United Kingdom1 site

  • St Bartholomew's Hospital

    London, Middlesex, EC1A 7BE

Other trials in United Kingdom

About this study

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.

Being tested
BLU-222, Carboplatin, Ribociclib, Fulvestrant
Keywords
CDK2, CCNE1, Platinum-resistance, Platinum-refractory, CDK4/6i, Ribociclib, Carboplatin, Fulvestrant, ER+ Breast Cancer
Medical subject headings
Ovarian Neoplasms, Endometrial Neoplasms, Stomach Neoplasms, Adenocarcinoma Of Esophagus, Carcinosarcoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • BLU-222Drug

    Oral administration

  • CarboplatinDrug

    IV Infusion

  • RibociclibDrug

    Oral administration

  • FulvestrantDrug

    Intra muscular administration

Study groups in NCT05252416
Study groupRoleWhat they receive
BLU-222 MonotherapyExperimentalDose Escalation: Multiple doses for BLU-222 for oral administration Dose Expansion: Oral dose of BLU-222 as determined during Dose Escalation
Receives: Drug: BLU-222
BLU-222 + CarboplatinExperimentalDose 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
Receives: Drug: BLU-222; Drug: Carboplatin
BLU-222 + Ribociclib + FulvestrantExperimentalDose 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
Receives: Drug: BLU-222; Drug: Ribociclib; Drug: Fulvestrant
BLU-222 + FulvestrantExperimentalDose Expansion: Oral dose of BLU-222 as determined during Dose Escalation + fulvestrant at the approved dose
Receives: Drug: BLU-222; Drug: Fulvestrant

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. [Phase 1] Determine the maximum tolerated dose (MTD) of BLU-222

    Measured: Approximately 21 months

  2. [Phase 1] Determine the recommended Phase 2 dose (RP2D) of BLU-222

    Measured: Approximately 21 months

  3. [Phase 1] Rate and severity of adverse events

    Measured: Approximately 21 months

  4. [Phase 2] Overall response rate (ORR)

    Measured: Approximately 43 months

  5. [Phase 2] Rate and severity of adverse events

    Measured: Approximately 43 months

Secondary outcomes (20)

  1. [Phase 1] Overall response rate (ORR)

    Measured: Approximately 21 months

  2. [Phase 1] Time of last quantifiable plasma drug concentration (Tlast)

    Measured: Approximately 21 months

  3. [Phase 1] Area under the plasma concentration time curve from time 0 to 12 hours (AUC0-12)

    Measured: Approximately 21 months

  4. [Phase 1] Area under the plasma concentration time curve from time 0 to 24 hours (AUC0-24)

    Measured: Approximately 21 months

  5. [Phase 1] Trough concentration (Ctrough)

    Measured: Approximately 21 months

  6. [Phase 1] Apparent volume of distribution (Vz/F)

    Measured: Approximately 21 months

  7. [Phase 1] Terminal elimination half-life (t½)

    Measured: Approximately 21 months

  8. [Phase 1] Apparent oral clearance(CL/F)

    Measured: Approximately 21 months

  9. [Phase 1] Accumulation ratio (R)

    Measured: Approximately 21 months

  10. [Phase 1] To assess treatment-induced modulation of biomarkers

    Measured: Approximately 21 months

  11. [Phase 1 and Phase 2] Duration of Response (DOR)

    Measured: Approximately 43 months

  12. [Phase 1 and Phase 2] Disease control rate (DCR)

    Measured: Approximately 43 months

  13. [Phase 1 and Phase 2] Clinical benefit rate (CBR)

    Measured: Approximately 43 months

  14. [Phase 1 and Phase 2] Progression free survival (PFS)

    Measured: Approximately 43 months

  15. [Phase 1 and Phase 2] Change in CA-125 levels

    Measured: Approximately 43 months

  16. [Phase 1 and Phase 2] Maximum plasma drug concentration (Cmax)

    Measured: Approximately 43 months

  17. [Phase 1 and Phase 2] Time to maximum plasma drug concentration (Tmax)

    Measured: Approximately 43 months

  18. [Phase 1 and Phase 2] Last measurable concentration (Clast)

    Measured: Approximately 43 months

  19. [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)

    Measured: Approximately 43 months

  20. [Phase 2] Overall survival (OS)

    Measured: Approximately 43 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted23 Feb 2022
  2. Study start7 Apr 2022
  3. Primary completion4 Jul 2025
  4. Study completion4 Jul 2025

Why it stopped: This trial was terminated prior to the initiation of Phase 2 for reasons not due to safety concerns.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
50 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05252416
Sponsor's protocol ID
BLU-222-1101
Status last verified
Nov 2025
First submitted
25 Jan 2022
Last updated
28 Nov 2025
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing BLU-222, Carboplatin and Ribociclib in people with Advanced Solid Tumors and HR+ Breast Cancer, run by Blueprint Medicines Corporation at 23 sites in 3 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 28 Nov 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 23 sites in United States, Italy, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: This trial was terminated prior to the initiation of Phase 2 for reasons not due to safety concerns.). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

[Phase 1] Determine the maximum tolerated dose (MTD) of BLU-222 (time frame: Approximately 21 months). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05252416.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Nov 2025.

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