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Lung Neoplasm MalignantPhase 1NCT05241873

(Concerto) Study of BLU-451 in Advanced Cancers With EGFR Exon 20 Insertion Mutations

A Phase 1 study testing BLU-451, Carboplatin and Pemetrexed in people with Lung Neoplasm Malignant and Carcinoma, Non-Small-Cell Lung, run by Blueprint Medicines Corporation at 23 sites in 5 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
Search all trials

Trial summary

This is a Phase 1/2, open-label first-in-human study of the safety, pharmacokinetics (PK), pharmacodynamics, and anti-tumor activity of BLU-451 monotherapy and BLU-451 in combination with platinum-based chemotherapy (carboplatin and pemetrexed). All participants will receive BLU-451 on a 21-day treatment cycle. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
BLU-451, Carboplatin and Pemetrexed
Could I receive a placebo?
No, everyone receives an active treatment
How many people
103 participants
Where
23 sitesin 5 countries
Study dates
4 Mar 2022to 31 Jul 2024
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
  • 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.
  • Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
  • 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.
  • Adequate hematological, renal, and hepatic function:
Show all 13Show fewer
  • Participants in 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).
  • Must have evaluable or measurable disease per RECIST v1.1.
  • Progression on or after or intolerance to most recent systemic therapy.
  • Participants in Phase 2
  • Histologically or cytologically confirmed metastatic NSCLC (stage IVA and IVB per AJCC 8th edition).
  • Must have measurable disease by RECIST 1.1.

Who cannot join

  • Have disease that is suitable for local therapy administered with curative intent.
  • 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.
  • Have NSCLC with mixed cell histology or a tumor with known histologic transformation (NSCLC to SCLC, SCLC to NSCLC, or epithelial to mesenchymal transition).
  • Other protocol-defined inclusion and exclusion criteria apply

Trial locations and contacts

23 sites in 5 countries.

23 sites in 5 countries

United States13 sites

  • University of Colorado Hospital - Anschutz Cancer Pavilion (ACP)

    Aurora, Colorado, 80045

  • Massachusetts General Hospital

    Boston, Massachusetts, 02114

  • Dana-Farber Cancer Institute

    Boston, Massachusetts, 02215

  • Northwestern Memorial Hospital

    Chicago, Illinois, 60611

  • City of Hope (City of Hope National Medical Center, City of Hope Medical Center)

    Duarte, California, 91010

  • New Experimental Therapeutics of Virginia (NEXT Oncology)

    Fairfax, Virginia, 22031

  • The University of Texas M.D. Anderson Cancer Center

    Houston, Texas, 77030-4009

  • Cedars-Sinai Medical Center, Samuel Oschin Comprehensive Cancer Institute

    Los Angeles, California, 90048

  • Laura & Isaac Perlmutter Cancer Center at NYU Langone Health

    New York, New York, 10016

  • Memorial Sloan Kettering Cancer Center

    New York, New York, 10065

  • Hospital of the University of Pennsylvania

    Philadelphia, Pennsylvania, 19104

  • Fred Hutchinson Cancer Center

    Seattle, Washington, 98109

  • Georgetown University Medical Center

    Washington D.C., District of Columbia, 20007

Other trials in United States

Taiwan4 sites

  • Taichung Veterans General Hospital

    Taichung, 1650

  • National Taiwan University Hospital

    Taipei, 100

  • Taipei Veterans General Hospital

    Taipei, 112

  • Linkou Chang Gung Memorial Hospital (CGMHLK)

    Taoyuan, 333

Other trials in Taiwan

Japan3 sites

  • National Cancer Center Hospital

    Chuo-ku, Tokyo, 104-0045

  • National Cancer Center Hospital East

    Kashiwa, Chiba, 277-8577

  • Kanagawa Cancer Center

    Yokohama, Kanagawa, 241-8515

Other trials in Japan

South Korea2 sites

  • Severance Hospital, Yonsei University Health System

    Seoul, 03722

  • Asan Medical Center

    Seoul, 05505

Other trials in South Korea

Canada1 site

  • Princess Margaret Cancer Centre

    Toronto, Ontario, M5G 2M9

Other trials in Canada

About this study

Official title: Phase I/II Study of BLU-451 in Advanced Cancers With EGFR Exon 20 Insertion Mutations

This is a Phase 1/2, open-label first-in-human study of the safety, pharmacokinetics (PK), pharmacodynamics, and anti-tumor activity of BLU-451 monotherapy and BLU-451 in combination with platinum-based chemotherapy (carboplatin and pemetrexed). All participants will receive BLU-451 on a 21-day treatment cycle.

Read the detailed description

The study is a Phase 1/2 Study of BLU-451 in Advanced Cancers with Epidermal growth factor receptor (EGFR) Exon 20 Insertion Mutations (Ex20ins). The study has two phases:

An initial Phase 1 portion will enroll participants with metastatic cancer with EGFR Ex20ins or other selected EGFR mutations that have progressed after prior systemic therapies and will determine the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D) of BLU-451.

Part 1B dose-escalation will enroll participants with metastatic Non-small Cell Lung Cancer (NSCLC) in the USA only to determine the MTD and/or RP2D of BLU-451 in combination with carboplatin and pemetrexed.

A Phase 2 portion will further evaluate the efficacy and safety of BLU-451 as monotherapy at RP2D in participants with NSCLC.

Being tested
BLU-451, Carboplatin, Pemetrexed
Keywords
protein kinase inhibitors, thoracic neoplasms
Medical subject headings
Lung Neoplasms, Carcinoma, Non-Small-Cell Lung, Respiratory Tract Neoplasms, Neoplasms, Neoplasms by Site, Lung Diseases, Respiratory Tract Diseases, Carcinoma, Bronchogenic

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • BLU-451Drug

    BLU-451 will be administered orally by tablet QD or BID on a 21-day treatment cycle

  • CarboplatinDrug

    Carboplatin will be administered intravenously (IV) on Day 1 of each cycle (every 3 weeks) for 4 to 6 cycles

  • PemetrexedDrug

    Pemetrexed will be administered prior to carboplatin as an IV infusion on Day 1 of each cycle (every 3 weeks)

Study groups in NCT05241873
Study groupRoleWhat they receive
Phase I - Part 1A Dose EscalationExperimentalBLU-451 monotherapy with dose escalation in participants with metastatic cancer with EGFR Ex20ins or other selected EGFR mutations that have progressed after prior systemic therapies.
Receives: Drug: BLU-451
Phase I - Part 1B Dose Escalation (US only)ExperimentalBLU-451 with dose escalation in combination with carboplatin and pemetrexed in participants with metastatic NSCLC with common EGFR mutations. This arm will enroll participants only in the United States.
Receives: Drug: BLU-451; Drug: Carboplatin; Drug: Pemetrexed
Phase I - Part 2 BLU-451 Monotherapy EnrichmentExperimentalBLU-451 enrichment at select doses.
Receives: Drug: BLU-451
Phase II - Cohort 2AExperimentalEGFR Ex20ins participants who have previously received platinum-based chemotherapy and either amivantamab or mobocertinib will receive BLU-451.
Receives: Drug: BLU-451
Phase II - Cohort 2BExperimentalEGFR Ex20ins participants who have previously received platinum-based chemotherapy but have not received a prior EGFR Ex20ins-targeted agent will receive BLU-451.
Receives: Drug: BLU-451
Phase II - Cohort 2CExperimentalEGFR Ex20ins participants with at least one measurable lesion in brain per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 who have previously received platinum-based chemotherapy will receive BLU-451. Previous treatment with EGFR Ex20Ins-targeted therapies is allowed but not required.
Receives: Drug: BLU-451
Phase II - Cohort 2DExperimentalParticipants with EGFR Ex20ins who have previously received platinum-based chemotherapy and both amivantamab AND mobocertinib, OR received any investigational Ex20Ins targeted agent(s) will receive BLU-451. Participants with Ex20ins or atypical mutations enrolled in other cohorts and who have other oncogenic drivers by central testing at baseline will be moved to this arm.
Receives: Drug: BLU-451
Phase II - Cohort 2EExperimentalParticipants with EGFR Ex20ins who have not received prior systemic therapy in metastatic setting will receive BLU-451.
Receives: Drug: BLU-451
Phase II - Cohort 2FExperimentalParticipants with EGFR atypical mutations (e.g., G719X, L861Q) who have previously received at least one EGFR tyrosine kinase inhibitor (TKI) will receive BLU-451. Participants with with other atypical EGFR mutations, such as S768I, may be enrolled if approved by Sponsor Medical Monitor.
Receives: Drug: BLU-451
Phase II - Cohort 2GExperimentalParticipants with EGFR atypical mutations (e.g., G719X, L861Q) who have not received prior systemic therapy in metastatic setting will receive BLU-451. Participants with with other atypical EGFR mutations, such as S768I, may be enrolled if approved by Sponsor Medical Monitor.
Receives: Drug: BLU-451

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Phase I - Determine the maximum tolerated dose (MTD) of BLU-451

    MTD determination: Dose-limiting toxicities (DLTs) rate

    Measured: 12-15 Months

  2. Phase I - Determine the Recommended Phase 2 Dose (RP2D) of BLU-451

    RP2D determination: DLT, PK, PD, and preliminary safety data

    Measured: 12-15 Months

  3. Phase I - Rate and severity of Adverse Events (AEs) of BLU-451

    Measured: 12-15 Months

  4. Phase II - The Overall Response Rate (ORR) rate of BLU-451

    ORR is defined as the proportion of subjects with objective response of CR or PR as determined by the Investigator using RECIST v1.1.

    Measured: Up to 30 months

Secondary outcomes (17)

  1. Phase I - The Overall Response Rate (ORR) rate of BLU-451

    ORR is defined as the proportion of subjects with objective response of CR or PR as determined by the Investigator using RECIST v1.1.

    Measured: Up to 30 months

  2. Phase I & II - The Duration of Response (DOR) rate of BLU-451

    DOR is defined as the time from the first objective response (CR or PR) to documented PD per RECIST v1.1 or death within 30 days of last dose of BLU-451 from any cause.

    Measured: 12-15 Months

  3. Phase I & II - The Disease Control Rate (DCR) rate of BLU-451

    DCR is defined as best response of CR, PR, non-CR/non-PD (for subjects who have only non-target lesions), or SD per RECIST v1.1.

    Measured: 12-15 Months

  4. Phase I & II - The Clinical Benefit Rate (CBR) of BLU-451

    CBR is defined as confirmed response of CR or PR, or stable disease with a duration of at least 16 weeks from the first dose date.

    Measured: 12-15 Months

  5. Phase I & II - The Progression Free Survival (PFS) rate of BLU-451

    PFS is defined as the time from the first BLU-451 dose until the date of death or the date of progression of disease or death, respectively.

    Measured: 12-15 Months

  6. Phase I & II - The Overall Survival (OS) rate of BLU-451

    OS is defined as the time from the first BLU-451 dose until the date of death or the date of progression of disease or death, respectively.

    Measured: 12-15 Months

  7. Phase I & II - To evaluate the Central Nervous System (CNS) Overall Response Rate (ORR) of BLU-451 in subjects with measurable baseline brain metastases

    CNS ORR: Defined as the proportion of patients achieving confirmed intra-cranial CR or PR as determined by the RECIST v1.1.

    Measured: Up to 30 months

  8. Phase I & II - To evaluate the Central Nervous System (CNS) Duration of Response (DOR) of BLU-451 in subjects with measurable baseline brain metastases

    CNS DOR: Defined as the the time from the first objective intra-cranial response (CR or PR) to documented PD in patients with measurable baseline brain metastases

    Measured: Up to 30 months

  9. Phase I & II - To evaluate the Central Nervous System (CNS) Progression Free Survival (PFS) of BLU-451 in subjects with measurable baseline brain metastases

    CNS PFS: Defined as the time from the first BLU-451 dose until the date of death or the date of intra-cranial progression of disease or death, respectively in patients with measurable baseline brain metastases

    Measured: Up to 30 months

  10. Phase I - Assess treatment-induced modulation of EGFR pathway biomarkers

    Profile pharmacodynamic changes in gene expression levels of the EGFR pathway biomarkers dual specificity phosphatase (DUSP6) and sprouty RTK signaling antagonist 4 (SPRY4)

    Measured: 12-15 Months

  11. Phase I & II - To evaluate the maximum observed blood drug concentration (Cmax) of BLU-451

    Measured: Up to 30 months

  12. Phase I & II - To evaluate the time of maximum blood concentration (tmax) of BLU-451

    Measured: Up to 30 months

  13. Phase I & II - To evaluate the elimination half life (t1/2) of BLU-451

    Measured: Up to 30 months

  14. Phase I & II - To evaluate the area under the blood concentration-time curve (AUC0-t, AUC0-inf) of BLU-451

    Measured: Up to 30 months

  15. Phase I & II - To evaluate the clearance (CL/F) of BLU-451

    Measured: Up to 30 months

  16. Phase I & II - To evaluate the volume of distribution (Vss/F) of BLU-451

    Measured: Up to 30 months

  17. Phase II - Rate and severity of Adverse Events (AEs) of BLU-451

    Measured: Up to 30 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted16 Feb 2022
  2. Study start4 Mar 2022
  3. Primary completion31 Jul 2024
  4. Study completion31 Jul 2024

Why it stopped: Sponsor decision, not related to safety concerns

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Model description
The primary objectives of this study are in Phase 1 to identify the MTD and/or RP2D of BLU-451, and in Phase 2, to evaluate the anti-tumor activity of BLU-451.
Masking
None (open label)
Enrolment
103 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05241873
Sponsor's protocol ID
BLU-451-1101
Status last verified
Feb 2025
First submitted
31 Jan 2022
Last updated
10 Feb 2025
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing BLU-451, Carboplatin and Pemetrexed in people with Lung Neoplasm Malignant and Carcinoma, Non-Small-Cell Lung, run by Blueprint Medicines Corporation at 23 sites in 5 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 13 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 10 Feb 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 23 sites in United States, Taiwan, Japan, South Korea, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: Sponsor decision, not related to safety concerns). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Phase I - Determine the maximum tolerated dose (MTD) of BLU-451 (time frame: 12-15 Months). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05241873.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Feb 2025.

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