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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Blueprint Medicines Corp.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

9 Jan 2024 → 4 Jul 2025

Decision date (initial)

2023-10-03

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Blueprint Medicines Corporation

External identifiers

EU CT number

2022-502528-29-00

ClinicalTrials.gov

NCT05252416

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Pharmacogenetic, Dose response, Therapy, Pharmacodynamic, Pharmacokinetic, Safety

Phase 1:
• To determine the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) of BLU-222 monotherapy and in combination with carboplatin or ribociclib and fulvestrant.
• To evaluate the safety and tolerability of BLU-222 monotherapy and in combination with carboplatin or ribociclib and fulvestrant.
Phase 2 :
• To assess the anticancer activity of BLU-222 at the RP2D in patients with advanced solid tumors, as a monotherapy and in combination with carboplatin, fulvestrant, or ribociclib and fulvestrant.
• To evaluate the safety and tolerability of BLU222 monotherapy and in combination with carboplatin, fulvestrant, or ribociclib and fulvestrant

Secondary objectives 1

1. Phase 1 : • To assess anticancer activities of BLU-222 monotherapy and in combination with carboplatin, or ribociclib and fulvestrant • To characterize the PK profile of BLU-222 monotherapy and in combination with carboplatin, or ribociclib and fulvestrant and correlate drug exposure with safety assessments and antitumor activity • To evaluate the effect of a high-fat meal on the PK of BLU-222 • To evaluate the relative bioavailability of 1st and 2nd generations of BLU-222 capsules • To assess treatment-induced modulation of cyclin E/CDK2 pathway biomarkers • To assess treatment-induced modulation of CA-125 in ovarian cancer Phase 2 : • To further characterize the PK profile of BLU-222 monotherapy and in combination with carboplatin, fulvestrant, or ribociclib • To assess additional measures of anticancer activity at the RP2D in patients with advanced solid tumors, as a monotherapy and in combination with carboplatin, fulvestrant, or ribociclib and fulvestrant. • To assess treatment-induced modulation of CA-125 in ovarian cancer.

Conditions and MedDRA coding

HR+ Breast Cancer CCNE1 Amplification HER2-negative Breast Cancer Advanced Solid Tumor Ovarian Cancer Endometrial Cancer Gastric Cancer

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 1

1. 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 5)CCNE1 amplified tumors that have progressed beyond standard of care

Exclusion criteria 15

1. 1. Have visceral crisis, lymphangitic spread, or leptomeningeal carcinomatosis.
2. 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. 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. 4. Have known intracranial hemorrhage and/or bleeding diatheses.
5. 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. 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. 7. Have mean resting QTcF > 450 msec, a history of prolonged QT syndrome or Torsades de pointes, or a familial history of prolonged QT syndrome.
8. 8. Have clinically significant, uncontrolled, cardiovascular diseaseincluding 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 thirddegree heart block).
9. 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. 10. Have active, uncontrolled infection (viral, bacterial, or fungal), including tuberculosis, hepatitis B virus (HBV), hepatitis C virus, AIDSrelated illness, or COVID-19 infection (symptoms and a positive test result).
11. 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. 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. 13. Unwilling or unable to comply with scheduled visits, study drug administration plan, laboratory tests, or other study procedures and study restrictions.
14. 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. 15. Patient is a pregnant female

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Phase 1: • MTD determination: DLT rate; • RP2D determination: DLT, PK, pharmacodynamics, and preliminary safety data. • Overall safety profile of BLU-222, as assessed by the TEAEs, changes in vital signs, ECGs, and clinical laboratory parameters
2. Phase 2: • Overall response rate (ORR), defined as the proportion of patients with confirmed CR or PR according to RECIST v1.1; • Overall safety profile of BLU-222, as assessed by the TEAEs, changes in vital signs, ECGs, and clinical laboratory parameters.

Secondary endpoints 17

1. Phase 1: 1. ORR, defined in Section 3.1.
2. 2. DOR, defined as the time from first documented response of either CR or PR to the date of first documented progressive disease or death due to any cause, whichever occurs first. DOR will be analyzed for patients with confirmed CR or PR.
3. 3. DCR, defined as the proportion of patients with confirmed CR, PR, or stable disease according to RECIST v1.1
4. 4. CBR, defined as the proportion of patients with confirmed CR, PR, or stable disease which the stable disease has been lasting ≥ 16 weeks from first dose date according to RECIST v1.1
5. 5. PFS, defined as the time from the first dose of BLU-222 until the date of first documented progressive disease or death due to any cause, whichever occurs first
6. 6. PK parameters of BLU-222 will include, as appropriate, Cmax, Tmax, Tlast, AUC0-24 for QD and AUC0-12 for BID, Ctrough, Vz/F, t½, CL/F, and accumulation ratio
7. 7. Correlations between PK parameters and safety findings of interest will be evaluated.
8. 8. Correlations between PK parameters and antitumor activity endpoints findings of interest will be evaluated.
9. 9. PK parameters of single oral doses of BLU-222 administered with or without a high-fat meal in patients, including Cmax, Tmax, AUC0-last measurements
10. 10. PK parameters of single oral doses of BLU-222 administered as the 1st and 2nd generation capsules, including Cmax, Tmax, AUC0-last
11. 11. Profile pharmacodynamic changes in the cyclin E/CDK2 pathway biomarker expression levels of phospho-Rb and other markers
12. 12. CA-125 response as defined by the GCIG CA-125 response criteria
13. Phase 2: 1. DOR, DCR, CBR (as defined for Phase 1 above). PFS, defined as the time from the first dose of BLU-222 until the date of first documented progressive disease or death due to any cause, whichever occurs first OS, defined as the time from the first dose of BLU-222 until the date of death due to any cause
14. 2. CA-125 response as defined by GCIG CA-125 response criteria
15. 3. PK parameters of BLU-222 will include, as appropriate, Cmax, Clast, Tmax or AUC0-last
16. 4. Correlations between PK parameters and safety findings of interest will be evaluated.
17. 5. Correlations between PK parameters and antitumor activity endpoints will be evaluated.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 5

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Blueprint Medicines Corp.

Sponsor organisation

Blueprint Medicines Corp.

Address

45 Sidney Street

City

Cambridge

Postcode

02139-4133

Country

United States

Scientific contact point

Organisation

Blueprint Medicines Corp.

Contact name

Tanya Green

Public contact point

Organisation

Blueprint Medicines Corp.

Contact name

Tanya Green

Third parties 11

Locations

4 EU/EEA countries · 12 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Application history

4 submissions — initial application plus substantial / non-substantial modifications