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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

Study Description
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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.

Condition or disease Intervention/treatment Phase
Advanced Solid Tumors HR+ Breast Cancer CCNE1 Amplification HER2-negative Breast Cancer Ovarian Cancer Endometrial Cancer Gastric Cancer Esophageal Adenocarcinoma Carcinosarcoma Drug: BLU-222 Drug: Carboplatin Drug: Ribociclib Drug: Fulvestrant Phase 1 Phase 2

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 366 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : April 7, 2022
Estimated Primary Completion Date : November 30, 2025
Estimated Study Completion Date : September 30, 2026

Resource links provided by the National Library of Medicine

Drug Information available for: Fulvestrant

Arms and Interventions
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Arm Intervention/treatment
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
 Drug: BLU-222
Oral administration
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

 Drug: BLU-222
Oral administration

Drug: Carboplatin
IV Infusion
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

 Drug: BLU-222
Oral administration

Drug: Ribociclib
Oral administration

Drug: Fulvestrant
Intra muscular administration
Experimental: BLU-222 + Fulvestrant
Dose Expansion: Oral dose of BLU-222 as determined during Dose Escalation + fulvestrant at the approved dose
 Drug: BLU-222
Oral administration

Drug: Fulvestrant
Intra muscular administration


Outcome Measures
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Primary Outcome Measures :
  1. [Phase 1] Determine the maximum tolerated dose (MTD) of BLU-222 [ Time Frame: Approximately 21 months ]
  2. [Phase 1] Determine the recommended Phase 2 dose (RP2D) of BLU-222 [ Time Frame: Approximately 21 months ]
  3. [Phase 1] Rate and severity of adverse events [ Time Frame: Approximately 21 months ]
  4. [Phase 2] Overall response rate (ORR) [ Time Frame: Approximately 43 months ]
  5. [Phase 2] Rate and severity of adverse events [ Time Frame: Approximately 43 months ]

Secondary Outcome Measures :
  1. [Phase 1] Overall response rate (ORR) [ Time Frame: Approximately 21 months ]
  2. [Phase 1] Time of last quantifiable plasma drug concentration (Tlast) [ Time Frame: Approximately 21 months ]
  3. [Phase 1] Area under the plasma concentration time curve from time 0 to 12 hours (AUC0-12) [ Time Frame: Approximately 21 months ]
  4. [Phase 1] Area under the plasma concentration time curve from time 0 to 24 hours (AUC0-24) [ Time Frame: Approximately 21 months ]
  5. [Phase 1] Trough concentration (Ctrough) [ Time Frame: Approximately 21 months ]
  6. [Phase 1] Apparent volume of distribution (Vz/F) [ Time Frame: Approximately 21 months ]
  7. [Phase 1] Terminal elimination half-life (t½) [ Time Frame: Approximately 21 months ]
  8. [Phase 1] Apparent oral clearance(CL/F) [ Time Frame: Approximately 21 months ]
  9. [Phase 1] Accumulation ratio (R) [ Time Frame: Approximately 21 months ]
  10. [Phase 1] To assess treatment-induced modulation of biomarkers [ Time Frame: Approximately 21 months ]
  11. [Phase 1 and Phase 2] Duration of Response (DOR) [ Time Frame: Approximately 43 months ]
  12. [Phase 1 and Phase 2] Disease control rate (DCR) [ Time Frame: Approximately 43 months ]
  13. [Phase 1 and Phase 2] Clinical benefit rate (CBR) [ Time Frame: Approximately 43 months ]
  14. [Phase 1 and Phase 2] Progression free survival (PFS) [ Time Frame: Approximately 43 months ]
  15. [Phase 1 and Phase 2] Change in CA-125 levels [ Time Frame: Approximately 43 months ]
  16. [Phase 1 and Phase 2] Maximum plasma drug concentration (Cmax) [ Time Frame: Approximately 43 months ]
  17. [Phase 1 and Phase 2] Time to maximum plasma drug concentration (Tmax) [ Time Frame: Approximately 43 months ]
  18. [Phase 1 and Phase 2] Last measurable concentration (Clast) [ Time Frame: 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) [ Time Frame: Approximately 43 months ]
  20. [Phase 2] Overall survival (OS) [ Time Frame: Approximately 43 months ]

Eligibility Criteria
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Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05252416


Contacts
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Contact: Blueprint Medicines 617-714-6707 medinfo@blueprintmedicines.com

Locations
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Sponsors and Collaborators
Blueprint Medicines Corporation
More Information
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Responsible Party: Blueprint Medicines Corporation
ClinicalTrials.gov Identifier: NCT05252416    
Other Study ID Numbers: BLU-222-1101
First Posted: February 23, 2022    Key Record Dates
Last Update Posted: April 23, 2024
Last Verified: April 2024
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Blueprint Medicines Corporation:
CDK2
CCNE1
Platinum-resistance
Platinum-refractory
CDK4/6i
 Ribociclib
Carboplatin
Fulvestrant
ER+ Breast Cancer
Additional relevant MeSH terms:
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Breast Neoplasms
Endometrial Neoplasms
Carcinosarcoma
Mixed Tumor, Mullerian
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Neoplasms by Histologic Type
Genital Diseases, Female
Female Urogenital Diseases
Female Urogenital Diseases and Pregnancy Complications
Urogenital Diseases
Genital Neoplasms, Female
Urogenital Neoplasms
 Genital Diseases
Uterine Neoplasms
Uterine Diseases
Neoplasms, Complex and Mixed
Sarcoma
Neoplasms, Connective and Soft Tissue
Carboplatin
Fulvestrant
Antineoplastic Agents
Antineoplastic Agents, Hormonal
Estrogen Receptor Antagonists
Estrogen Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs