Clinical trial NCT05252416: (VELA) Study of BLU-222 in Advanced Solid Tumors
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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
PHASE2
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
Lead sponsor: Blueprint Medicines Corporation
Sponsor class: INDUSTRY
First posted: 2022-02-23
Enrollment: 366
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: [Phase 1] Determine the maximum tolerated dose (MTD) of BLU-222
timeFrame: Approximately 21 months
measure: [Phase 1] Determine the recommended Phase 2 dose (RP2D) of BLU-222
timeFrame: Approximately 21 months
measure: [Phase 1] Rate and severity of adverse events
timeFrame: Approximately 21 months
measure: [Phase 2] Overall response rate (ORR)
timeFrame: Approximately 43 months
measure: [Phase 2] Rate and severity of adverse events
timeFrame: Approximately 43 months
Secondary outcomes:
measure: [Phase 1] Overall response rate (ORR)
timeFrame: Approximately 21 months
measure: [Phase 1] Time of last quantifiable plasma drug concentration (Tlast)
timeFrame: Approximately 21 months
measure: [Phase 1] Area under the plasma concentration time curve from time 0 to 12 hours (AUC0-12)
timeFrame: Approximately 21 months
measure: [Phase 1] Area under the plasma concentration time curve from time 0 to 24 hours (AUC0-24)
timeFrame: Approximately 21 months
measure: [Phase 1] Trough concentration (Ctrough)
timeFrame: Approximately 21 months
measure: [Phase 1] Apparent volume of distribution (Vz/F)
timeFrame: Approximately 21 months
measure: [Phase 1] Terminal elimination half-life (t½)
timeFrame: Approximately 21 months
measure: [Phase 1] Apparent oral clearance(CL/F)
timeFrame: Approximately 21 months
measure: [Phase 1] Accumulation ratio (R)
timeFrame: Approximately 21 months
measure: [Phase 1] To assess treatment-induced modulation of biomarkers
timeFrame: Approximately 21 months
measure: [Phase 1 and Phase 2] Duration of Response (DOR)
timeFrame: Approximately 43 months
measure: [Phase 1 and Phase 2] Disease control rate (DCR)
timeFrame: Approximately 43 months
measure: [Phase 1 and Phase 2] Clinical benefit rate (CBR)
timeFrame: Approximately 43 months
measure: [Phase 1 and Phase 2] Progression free survival (PFS)
timeFrame: Approximately 43 months
measure: [Phase 1 and Phase 2] Change in CA-125 levels
timeFrame: Approximately 43 months
measure: [Phase 1 and Phase 2] Maximum plasma drug concentration (Cmax)
timeFrame: Approximately 43 months
measure: [Phase 1 and Phase 2] Time to maximum plasma drug concentration (Tmax)
timeFrame: Approximately 43 months
measure: [Phase 1 and Phase 2] Last measurable concentration (Clast)
timeFrame: Approximately 43 months
measure: [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)
timeFrame: Approximately 43 months
measure: [Phase 2] Overall survival (OS)
timeFrame: Approximately 43 months
Other outcomes:
Locations:
city: Little Rock
country: United States
facility: University of Arkansas for Medical Sciences
state: Arkansas
city: San Francisco
country: United States
facility: UCSF Helen Diller Family Comprehensive Cancer Center
state: California
city: Stanford
country: United States
facility: Stanford Women's Cancer Center
state: California
city: Sarasota
country: United States
facility: Florida Cancer Specialists
state: Florida
city: Chicago
country: United States
facility: University of Chicago Medical Center
state: Illinois
city: Baltimore
country: United States
facility: Johns Hopkins Sidney Kimmel Comprehensive Cancer Center (SKCCC)
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: Detroit
country: United States
facility: Henry Ford Health System
state: Michigan
city: New York
country: United States
facility: Columbia University Herbert Irving Comprehensive Cancer Center
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: New York
country: United States
facility: Montefiore Medical Center
state: New York
city: Chapel Hill
country: United States
facility: UNC Hospitals at Chapel Hill - The University of North Carolina at Chapel Hill
state: North Carolina
city: Oklahoma City
country: United States
facility: OU Health Stephenson Cancer Center
state: Oklahoma
city: Philadelphia
country: United States
facility: Hospital of the Fox Chase Cancer Center
state: Pennsylvania
city: Nashville
country: United States
facility: Vanderbilt Breast Center at One Hundred Oaks
state: Tennessee
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah - Huntsman Cancer Institute - PPDS
state: Utah
city: Charlottesville
country: United States
facility: University of Virginia Comprehensive Cancer Center
state: Virginia
city: Milano
country: Italy
facility: Fondazione IRCCS Istituto Nazionale dei Tumori
city: Milano
country: Italy
facility: Instituto Europeo di Oncologia
city: Rome
country: Italy
facility: Fondazione Policlinico Universitario A Gemelli-Rome
city: London
country: United Kingdom
facility: St Bartholomew's Hospital
state: Middlesex
Study officials:
References: