Loading clinical trials...

(Concerto) Study of BLU-451 in Advanced Cancers With EGFR Exon 20 Insertion Mutations | Clinical Trials | Clareo Health

TERMINATEDPHASE1

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

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

NCT05241873•Blueprint Medicines Corporation

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.

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.

Eligibility

Age

18 - No limit years

Sex

ALL

Healthy Volunteers

Inclusion Criteria

•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:
•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.
+3 more criteria

Exclusion Criteria

•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).

Locations (23)

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

Duarte, California, United States

Cedars-Sinai Medical Center, Samuel Oschin Comprehensive Cancer Institute

Los Angeles, California, United States

University of Colorado Hospital - Anschutz Cancer Pavilion (ACP)

Aurora, Colorado, United States

Georgetown University Medical Center

Washington D.C., District of Columbia, United States

Northwestern Memorial Hospital

Chicago, Illinois, United States

Massachusetts General Hospital

Boston, Massachusetts, United States

Dana-Farber Cancer Institute

Boston, Massachusetts, United States

Laura & Isaac Perlmutter Cancer Center at NYU Langone Health

New York, New York, United States

Memorial Sloan Kettering Cancer Center

New York, New York, United States

Hospital of the University of Pennsylvania

Philadelphia, Pennsylvania, United States

Key Dates

Start Date

March 4, 2022

Primary Completion Date

July 31, 2024

Completion Date

July 31, 2024

Last Updated

February 10, 2025

Enrollment

103

ACTUAL participants

Conditions

Lung Neoplasm MalignantCarcinoma, Non-Small-Cell LungRespiratory Tract NeoplasmsNeoplasmsNeoplasms by SiteLung DiseasesRespiratory Tract DiseaseCarcinoma, BronchogenicBronchial NeoplasmsAdenocarcinomaCarcinomaNeoplasms by Histologic TypeEGFR Exon 20 MutationEGFR Exon 20 Insertion MutationEGFR Activating MutationAntineoplastic AgentsMetastatic Lung CancerBrain MetastasesEGFR-mutated NSCLCEGFR Atypical Mutations, Including G719X and L861Q

Interventions

BLU-451

DRUG

Carboplatin

DRUG

Pemetrexed

DRUG

KEYMAKER-U01 Umbrella Master Study: Studies of Investigational Agents With Either Pembrolizumab (MK-3475) Alone or With Pembrolizumab PLUS Chemotherapy in Participants With Non-small Cell Lung Cancer (NSCLC) (MK-3475-U01/KEYMAKER-U01)

NCT04165798

Carcinoma, Non-Small-Cell Lung

View study

RECRUITINGPHASE2

A Study of JNJ-90301900 in Combination With Chemoradiation Followed by Consolidation Immunotherapy for Non-Small Cell Lung Cancer (NSCLC)

NCT06667908

Carcinoma, Non-Small-Cell Lung

View study

RECRUITING

Data Source & Attribution

This clinical trial information is sourced from ClinicalTrials.gov, a service of the U.S. National Institutes of Health.

ClinicalTrials.gov last update: February 10, 2025Data synced to Clareo: March 29, 2026

Modifications: This data has been reformatted for display purposes. Eligibility criteria have been parsed into inclusion/exclusion sections. Location data has been geocoded to enable distance-based search. For the authoritative and most current information, please visit ClinicalTrials.gov.

Neither the United States Government nor Clareo Health make any warranties regarding the data. Check ClinicalTrials.gov frequently for updates.

View ClinicalTrials.gov Terms and Conditions

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

Inclusion Criteria

Exclusion Criteria

KEYMAKER-U01 Umbrella Master Study: Studies of Investigational Agents With Either Pembrolizumab (MK-3475) Alone or With Pembrolizumab PLUS Chemotherapy in Participants With Non-small Cell Lung Cancer (NSCLC) (MK-3475-U01/KEYMAKER-U01)

A Study of JNJ-90301900 in Combination With Chemoradiation Followed by Consolidation Immunotherapy for Non-Small Cell Lung Cancer (NSCLC)

A Study of Adagrasib Plus Pembrolizumab Plus Chemotherapy vs. Placebo Plus Pembrolizumab Plus Chemotherapy in Participants With Previously Untreated Non-squamous Non-small Cell Lung Cancer With KRAS G12C Mutation (KRYSTAL-4)

A Study of LY4175408 in Participants With Advanced Cancer

A Study to Learn About the Study Medicine Called PF-08634404 in Combination With Chemotherapy in Adult Participants With Locally Advanced or Metastatic Non-Small Cell Lung Cancer

A Study of Amivantamab in Combination With Lazertinib, or Amivantamab in Combination With Platinum-Based Chemotherapy, for Common Epidermal Growth Factor Receptor (EGFR)-Mutated Locally Advanced or Metastatic Non-Small Cell Lung Cancer (NSCLC)