Phase 1/2 Study of BLU-451 in certain advanced cancers

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]

Decision date (initial)

2023-10-10

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Blueprint Medicines Corporation

External identifiers

EU CT number

2022-502527-21-00

WHO UTN

U1111-1292-3957

ClinicalTrials.gov

NCT05241873

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Efficacy, Dose response, Others, Safety

Main Objective 1 Phase 1: To determine the Maximum Tolerated Dose (MTD) and/or Recommended Phase 2 Dose (RP2D) of BLU-451 monotherapy and in combination with platinum based chemotherapy
Main Objective 2 Phase 1: To characterize the safety and tolerability of BLU-451 monotherapy and in combination with platinum based chemotherapy
Main Objective 1 Phase 2: To evaluate the anti-tumor activity of BLU-451 monotherapy at the RP2D using RECIST v1.1

Secondary objectives 8

1. 1(Phase1). To evaluate the PK of BLU-451 monotherapy and in combination with platinum based chemotherapy and correlate drug exposure with safety assessments
2. 2(Phase1). To evaluate the anti-tumor activity of BLU-451 monotherapy and in combination with platinum based chemotherapy using Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1
3. 3(Phase1). To evaluate the CNS anti-tumor activity of BLU-451 monotherapy and in combination with platinum based chemotherapy in patients with measurable baseline brain metastases using the RECIST v1.1
4. 4(Phase1). To assess treatment-induced modulation of EGFR pathway biomarkers for BLU-451 monotherapy
5. 5(Phase2). To characterize the safety and tolerability of BLU-451 monotherapy
6. 6(Phase2). To assess additional measures of anti-tumor activity of BLU-451 monotherapy at the RP2D
7. 7(Phase2). To evaluate the CNS anti-tumor activity of BLU-451 monotherapy in patients with measurable baseline brain metastases using RECIST 1.1
8. 8(Phase2). To evaluate the PK of BLU-451

Conditions and MedDRA coding

Advanced cancers with EGFR Exon20 insertions mutations

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 10

1. 1. (All participants). Documented EGFR mutation, based on Next-generation sequencing (NGS) testing of tumor or liquid biopsy analyzed in a local Clinical Laboratory Improvement Amendments (CLIA) (or International Organization for Standardization (ISO) 15189)-certified or equivalent laboratory are required. Redacted copies of laboratory results must be available for Sponsor review.
2. 2. (All participants). Able to provide a new or archived pretreatment formalin-fixed, paraffin-embedded (FFPE) tumor sample. For participants who received EGFR-targeted therapy subsequent to the most recent archived biopsy, all efforts should be made to obtain a new biopsy unless it is not safe or feasible to obtain one.
3. 3. (All participants). Estado funcional según el Eastern Cooperative Oncology Group (ECOG) de 0 o 1.
4. 4. (All participants). Participants must be without seizures for at least 14 days prior to enrollment, and patients who receive treatment with anti-epileptic drugs must be on stable doses for at least 14 days prior to enrollment.
5. 5. (All participants). Adequate hematological, renal, and hepatic function.
6. 6. (Only Phase 1). Histologically or cytologically confirmed metastatic NSCLC (stage IVA and IVB per American Joint Committee on Cancer (AJCC) 8th edition) or other metastatic cancers except for primary CNS tumors (Part 1A or Part 2 only).
7. 7. (Only Phase 1). Must have evaluable or measurable disease per RECIST v1.1.
8. 8. (Only Phase 1). Progression on or after or intolerance to most recent systemic therapy.
9. 9. (Only Phase 2). Histologically or cytologically confirmed metastatic NSCLC (stage IVA and IVB per AJCC 8th edition).
10. 10. (Only Phase 2). Must have measurable disease by RECIST 1.1.

Exclusion criteria 3

1. 1. Have disease that is suitable for local therapy administered with curative intent.
2. 2. Have tumor that harbors known driver alterations (including, but not limited to ROS, BRAF V600E, ALK, RET, HER2, MET, KRAS, NTRK1/2/3, EGFR C797X, or EGFR T790M mutation). These criteria are not applicable to Phase 1 Part 1B.
3. 3. Have NSCLC with mixed cell histology or a tumor with known histologic transformation (NSCLC to SCLC, SCLC to NSCLC, or epithelial to mesenchymal transition).

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 4

1. 1. (Phase 1). Maximum tolerated dose (MTD) determination: Dose-limiting toxicity (DLT) rate
2. 2. (Phase 1). Recommended Phase 2 dose (RP2D) determination: DLT, PK, PD, and preliminary safety data
3. 3. (Phase 1). Overall safety profile as assessed by the type, frequency, severity, timing, and relationship to study drug of adverse events (AEs), and changes in vital signs, electrocardiograms, and safety laboratory tests
4. 4. (Phase 2). Objective Response Rate (ORR)

Secondary endpoints 8

1. 1. (Phase 1). Plasma concentrations of BLU-451 as a function of time post-dosing. C3PK parameters for single (first) dose and multiple doses
2. 2. (Phase 1). • ORR • DOR • Disease control rate (DCR) • Clinical benefit rate (CBR) • PFS • OS
3. 3. (Phase 1). • CNS ORR • CNS DOR • CNS PFS
4. 4. (Phase 1). Profile pharmacodynamic changes in gene expression levels of the EGFR pathway biomarkers dual specificity phosphatase (DUSP6) and sprouty RTK signaling antagonist 4 (SPRY4)
5. 5. (Phase 2). Safety profile as assessed by the type, frequency, severity, timing, and relationship to study drug of adverse events (AEs), and changes in vital signs, electrocardiograms, and safety laboratory tests
6. 6. (Phase 2). • DOR • DCR • CBR • PFS • OS
7. 7. (Phase 2). • CNS ORR • CNS DOR • CNS PFS
8. 8. (Phase 2). • Plasma concentrations of BLU-451 as a function of time post-dosing • PK parameters for single (first) dose and multiple doses

Investigational products

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

Test 3

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

Medical Information

Public contact point

Organisation

Blueprint Medicines Corp.

Contact name

Medical Information

Third parties 10

Locations

1 EU/EEA country · 4 investigational sites

By country

Investigational sites

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Urgent safety measures 1 · Art. 54 CTR

Application history

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