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

Ovarian Cancer Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05252416
• Other study ID #: BLU-222-1101
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: April 7, 2022
• Est. completion date: September 30, 2026

Study information

• Verified date: April 2024
• Source: Blueprint Medicines Corporation
• Contact: Blueprint Medicines
• Phone: 617-714-6707
• Email: medinfo[@]blueprintmedicines.com
• Is FDA regulated: No
• Study type: Interventional

Clinical 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 366
• Est. completion date: September 30, 2026
• Est. primary completion date: November 30, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Advanced Solid Tumors
• Breast Neoplasms
• Carcinosarcoma
• Endometrial Cancer
• Endometrial Neoplasms
• Esophageal Adenocarcinoma
• Gastric Cancer
• HER2-negative Breast Cancer
• Mixed Tumor, Mullerian
• Ovarian Cancer

Intervention

Drug:
• BLU-222
Oral administration
• Carboplatin
IV Infusion
• Ribociclib
Oral administration
• Fulvestrant
Intra muscular administration

Locations

Country	Name	City	State
Italy	Fondazione IRCCS Istituto Nazionale dei Tumori	Milano
Italy	Instituto Europeo di Oncologia	Milano
Italy	Fondazione Policlinico Universitario A Gemelli-Rome	Rome
United Kingdom	St Bartholomew's Hospital	London	Middlesex
United States	Johns Hopkins Sidney Kimmel Comprehensive Cancer Center (SKCCC)	Baltimore	Maryland
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	UNC Hospitals at Chapel Hill - The University of North Carolina at Chapel Hill	Chapel Hill	North Carolina
United States	University of Virginia Comprehensive Cancer Center	Charlottesville	Virginia
United States	University of Chicago Medical Center	Chicago	Illinois
United States	Henry Ford Health System	Detroit	Michigan
United States	MD Anderson Cancer Center	Houston	Texas
United States	University of Arkansas for Medical Sciences	Little Rock	Arkansas
United States	Vanderbilt Breast Center at One Hundred Oaks	Nashville	Tennessee
United States	Columbia University Herbert Irving Comprehensive Cancer Center	New York	New York
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	Montefiore Medical Center	New York	New York
United States	OU Health Stephenson Cancer Center	Oklahoma City	Oklahoma
United States	Hospital of the Fox Chase Cancer Center	Philadelphia	Pennsylvania
United States	University of Utah - Huntsman Cancer Institute - PPDS	Salt Lake City	Utah
United States	UCSF Helen Diller Family Comprehensive Cancer Center	San Francisco	California
United States	Florida Cancer Specialists	Sarasota	Florida
United States	Stanford Women's Cancer Center	Stanford	California

Sponsors (1)

Lead Sponsor	Collaborator
Blueprint Medicines Corporation

Countries where clinical trial is conducted

United States,  Italy,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	[Phase 1] Determine the maximum tolerated dose (MTD) of BLU-222		Approximately 21 months
Primary	[Phase 1] Determine the recommended Phase 2 dose (RP2D) of BLU-222		Approximately 21 months
Primary	[Phase 1] Rate and severity of adverse events		Approximately 21 months
Primary	[Phase 2] Overall response rate (ORR)		Approximately 43 months
Primary	[Phase 2] Rate and severity of adverse events		Approximately 43 months
Secondary	[Phase 1] Overall response rate (ORR)		Approximately 21 months
Secondary	[Phase 1] Time of last quantifiable plasma drug concentration (Tlast)		Approximately 21 months
Secondary	[Phase 1] Area under the plasma concentration time curve from time 0 to 12 hours (AUC0-12)		Approximately 21 months
Secondary	[Phase 1] Area under the plasma concentration time curve from time 0 to 24 hours (AUC0-24)		Approximately 21 months
Secondary	[Phase 1] Trough concentration (Ctrough)		Approximately 21 months
Secondary	[Phase 1] Apparent volume of distribution (Vz/F)		Approximately 21 months
Secondary	[Phase 1] Terminal elimination half-life (t½)		Approximately 21 months
Secondary	[Phase 1] Apparent oral clearance(CL/F)		Approximately 21 months
Secondary	[Phase 1] Accumulation ratio (R)		Approximately 21 months
Secondary	[Phase 1] To assess treatment-induced modulation of biomarkers		Approximately 21 months
Secondary	[Phase 1 and Phase 2] Duration of Response (DOR)		Approximately 43 months
Secondary	[Phase 1 and Phase 2] Disease control rate (DCR)		Approximately 43 months
Secondary	[Phase 1 and Phase 2] Clinical benefit rate (CBR)		Approximately 43 months
Secondary	[Phase 1 and Phase 2] Progression free survival (PFS)		Approximately 43 months
Secondary	[Phase 1 and Phase 2] Change in CA-125 levels		Approximately 43 months
Secondary	[Phase 1 and Phase 2] Maximum plasma drug concentration (Cmax)		Approximately 43 months
Secondary	[Phase 1 and Phase 2] Time to maximum plasma drug concentration (Tmax)		Approximately 43 months
Secondary	[Phase 1 and Phase 2] Last measurable concentration (Clast)		Approximately 43 months
Secondary	[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
Secondary	[Phase 2] Overall survival (OS)		Approximately 43 months