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

Study Purpose

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.

Recruitment Criteria

Accepts Healthy Volunteers Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms	No
Study Type An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes. An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes. Searching Both is inclusive of interventional and observational studies.	Interventional
Eligible Ages	18 Years and Over
Gender	All

More Inclusion & Exclusion Criteria

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.

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.

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).

Other protocol-defined inclusion and exclusion criteria apply

Trial Details

Trial ID: This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.	NCT05241873
Phase Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans. Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data. Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs. Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.	Phase 1/Phase 2
Lead Sponsor The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.	Blueprint Medicines Corporation
Principal Investigator The person who is responsible for the scientific and technical direction of the entire clinical study.	N/A
Principal Investigator Affiliation	N/A
Agency Class Category of organization(s) involved as sponsor (and collaborator) supporting the trial.	Industry
Overall Status	Active, not recruiting
Countries	Canada, Japan, Korea, Republic of, Taiwan, United States
Conditions The disease, disorder, syndrome, illness, or injury that is being studied.	Lung Neoplasm Malignant, Carcinoma, Non-Small-Cell Lung, Respiratory Tract Neoplasms, Neoplasms, Neoplasms by Site, Lung Diseases, Respiratory Tract Disease, Carcinoma, Bronchogenic, Bronchial Neoplasms, Adenocarcinoma, Carcinoma, Neoplasms by Histologic Type, EGFR Exon 20 Mutation, EGFR Exon 20 Insertion Mutation, EGFR Activating Mutation, Antineoplastic Agents, Metastatic Lung Cancer, Brain Metastases, EGFR-mutated NSCLC, EGFR Atypical Mutations, Including G719X and L861Q

Additional Details

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.

Arms & Interventions

Arms

Experimental: Phase I - Part 1A Dose Escalation

BLU-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.

Experimental: Phase I - Part 1B Dose Escalation (US only)

BLU-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.

Experimental: Phase I - Part 2 BLU-451 Monotherapy Enrichment

BLU-451 enrichment at select doses.

Experimental: Phase II - Cohort 2A

EGFR Ex20ins participants who have previously received platinum-based chemotherapy and either amivantamab or mobocertinib will receive BLU-451.

Experimental: Phase II - Cohort 2B

EGFR Ex20ins participants who have previously received platinum-based chemotherapy but have not received a prior EGFR Ex20ins-targeted agent will receive BLU-451.

Experimental: Phase II - Cohort 2C

EGFR 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.

Experimental: Phase II - Cohort 2D

Participants 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.

Experimental: Phase II - Cohort 2E

Participants with EGFR Ex20ins who have not received prior systemic therapy in metastatic setting will receive BLU-451.

Experimental: Phase II - Cohort 2F

Participants 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.

Experimental: Phase II - Cohort 2G

Participants 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.

Interventions

Drug: - BLU-451

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

Drug: - Carboplatin

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

Drug: - Pemetrexed

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

Contact a Trial Team

If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.

Duarte, California

Status

Address

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

Duarte, California, 91010

Los Angeles, California

Status

Address

Cedars-Sinai Medical Center, Samuel Oschin Comprehensive Cancer Institute

Los Angeles, California, 90048

Aurora, Colorado

Status

Address

University of Colorado Hospital - Anschutz Cancer Pavilion (ACP)

Aurora, Colorado, 80045

Georgetown University Medical Center, Washington, District of Columbia

Status

Address

Georgetown University Medical Center

Washington, District of Columbia, 20007

Northwestern Memorial Hospital, Chicago, Illinois

Status

Address

Northwestern Memorial Hospital

Chicago, Illinois, 60611

Massachusetts General Hospital, Boston, Massachusetts

Status

Address

Massachusetts General Hospital

Boston, Massachusetts, 02114

Dana-Farber Cancer Institute, Boston, Massachusetts

Status

Address

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215

New York, New York

Status

Address

Laura & Isaac Perlmutter Cancer Center at NYU Langone Health

New York, New York, 10016

Memorial Sloan Kettering Cancer Center, New York, New York

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Address

Memorial Sloan Kettering Cancer Center

New York, New York, 10065

Philadelphia, Pennsylvania

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Address

Hospital of the University of Pennsylvania

Philadelphia, Pennsylvania, 19104

Houston, Texas

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Address

The University of Texas M.D. Anderson Cancer Center

Houston, Texas, 77030-4009

Fairfax, Virginia

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Address

New Experimental Therapeutics of Virginia (NEXT Oncology)

Fairfax, Virginia, 22031

Fred Hutchinson Cancer Center, Seattle, Washington

Status

Address

Fred Hutchinson Cancer Center

Seattle, Washington, 98109

International Sites

Princess Margaret Cancer Centre, Toronto, Ontario, Canada

Status

Address

Princess Margaret Cancer Centre

Toronto, Ontario, M5G 2M9

National Cancer Center Hospital East, Kashiwa, Chiba, Japan

Status

Address

National Cancer Center Hospital East

Kashiwa, Chiba, 277-8577

Kanagawa Cancer Center, Yokohama-shi, Kanagawa, Japan

Status

Address

Kanagawa Cancer Center

Yokohama-shi, Kanagawa, 241-8515

National Cancer Center Hospital, Chuo-ku, Tokyo, Japan

Status

Address

National Cancer Center Hospital

Chuo-ku, Tokyo, 104-0045

Seoul, Korea, Republic of

Status

Address

Severance Hospital, Yonsei University Health System

Seoul, , 03722

Asan Medical Center, Seoul, Korea, Republic of

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Address

Asan Medical Center

Seoul, , 05505

Taichung Veterans General Hospital, Taichung, Taiwan

Status

Address

Taichung Veterans General Hospital

Taichung, , 1650

National Taiwan University Hospital, Taipei City, Taiwan

Status

Address

National Taiwan University Hospital

Taipei City, , 100

Taipei Veterans General Hospital, Taipei, Taiwan

Status

Address

Taipei Veterans General Hospital

Taipei, , 112

Taoyuan, Taiwan

Status

Address

Linkou Chang Gung Memorial Hospital (CGMHLK)

Taoyuan, , 333

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