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

NCT05252416 | Terminated Phase 1 DMC FDA Drug

• 1 other identifier: BLU-222-1101
• Study Type: interventional
• Target: 50
• Locations: 3 countries
• Sites: 23

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.

Conditions

Advanced Solid Tumors; HR+ Breast Cancer; CCNE1 Amplification; HER2-negative Breast Cancer; Ovarian Cancer; Endometrial Cancer; Gastric Cancer; Esophageal Adenocarcinoma; Carcinosarcoma

Keywords

CDK2; CCNE1; Platinum-resistance; Platinum-refractory; CDK4/6i; Ribociclib; Carboplatin; Fulvestrant; ER+ Breast Cancer

Outcome Measures

Primary Outcomes (5)

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

  Approximately 21 months

• [Phase 1] Determine the recommended Phase 2 dose (RP2D) 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 Outcomes (20)

• [Phase 1] Overall response rate (ORR)

  Approximately 21 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] 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

Study Arms (4)

BLU-222 Monotherapy

EXPERIMENTAL

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

BLU-222 + Carboplatin

EXPERIMENTAL

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; Drug: Carboplatin

BLU-222 + Ribociclib + Fulvestrant

EXPERIMENTAL

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; Drug: Ribociclib; Drug: Fulvestrant

BLU-222 + Fulvestrant

EXPERIMENTAL

Dose Expansion: Oral dose of BLU-222 as determined during Dose Escalation + fulvestrant at the approved dose

Drug: BLU-222; Drug: Fulvestrant

Interventions

BLU-222 DRUG

Oral administration

BLU-222 + Carboplatin; BLU-222 + Fulvestrant; BLU-222 + Ribociclib + Fulvestrant; BLU-222 Monotherapy

Carboplatin DRUG

IV Infusion

BLU-222 + Carboplatin

Ribociclib DRUG

Oral administration

BLU-222 + Ribociclib + Fulvestrant

Fulvestrant DRUG

Intra muscular administration

BLU-222 + Fulvestrant; BLU-222 + Ribociclib + Fulvestrant

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• Have visceral crisis, lymphangitic spread, or leptomeningeal carcinomatosis.
• 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.
• 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.
• 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

Sponsors & Collaborators

• Blueprint Medicines Corporation: lead

Study Sites (23)

University of Arkansas for Medical Sciences

Little Rock, Arkansas, 72205, United States

Location

UCSF Helen Diller Family Comprehensive Cancer Center

San Francisco, California, 94158, United States

Location

Stanford Women's Cancer Center

Stanford, California, 94305, United States

Location

Florida Cancer Specialists

Sarasota, Florida, 34232, United States

Location

University of Chicago Medical Center

Chicago, Illinois, 60637, United States

Location

Johns Hopkins Sidney Kimmel Comprehensive Cancer Center (SKCCC)

Baltimore, Maryland, 21287, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Henry Ford Health System

Detroit, Michigan, 48202, United States

Location

Columbia University Herbert Irving Comprehensive Cancer Center

New York, New York, 10032, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Montefiore Medical Center

New York, New York, 10461, United States

Location

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

Chapel Hill, North Carolina, 27514, United States

Location

OU Health Stephenson Cancer Center

Oklahoma City, Oklahoma, 73104, United States

Location

Hospital of the Fox Chase Cancer Center

Philadelphia, Pennsylvania, 19111, United States

Location

Vanderbilt Breast Center at One Hundred Oaks

Nashville, Tennessee, 37204, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

University of Utah - Huntsman Cancer Institute - PPDS

Salt Lake City, Utah, 84112, United States

Location

University of Virginia Comprehensive Cancer Center

Charlottesville, Virginia, 22903, United States

Location

Fondazione IRCCS Istituto Nazionale dei Tumori

Milan, 20133, Italy

Location

Instituto Europeo di Oncologia

Milan, 20141, Italy

Location

Fondazione Policlinico Universitario A Gemelli-Rome

Rome, 00168, Italy

Location

St Bartholomew's Hospital

London, Middlesex, EC1A 7BE, United Kingdom

Location

MeSH Terms

Conditions

Ovarian Neoplasms; Endometrial Neoplasms; Stomach Neoplasms; Adenocarcinoma Of Esophagus; Carcinosarcoma

Interventions

Carboplatin; ribociclib; Fulvestrant

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders; Uterine Neoplasms; Uterine Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases; Neoplasms, Complex and Mixed; Neoplasms by Histologic Type; Sarcoma; Neoplasms, Connective and Soft Tissue

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Estradiol; Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 25, 2022
• First Posted: February 23, 2022
• Study Start: April 7, 2022
• Primary Completion: July 4, 2025
• Study Completion: July 4, 2025
• Last Updated: November 28, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

IT (3); US (19); GB (1)