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NCT06706076PHASE1, PHASE2Recruiting

A Study of BH-30643 in Subjects With Locally Advanced or Metastatic NSCLC Harboring EGFR and/or HER2 Mutations

BlossomHill Therapeutics

Start Date

1/9/2025

Completion Date

7/31/2029

Summary

This Phase1/2, open label, multicenter study will assess the safety, tolerability, pharmacokinetics (PK), pharmacodynamics and preliminary anti-tumor activity of BH-30643 in patients with NSCLC having EGFR and/or HER2 mutations. Phase 1 will determine the recommended Phase 2 dose (RP2D) and, if applicable, the maximum tolerated dose (MTD) of BH-30643. Phase 2 will further evaluate the antitumor efficacy and safety in specified cohorts determined by EGFR/HER2 mutation subtypes and/or treatment history at the RP2D, as well as the population PK.

Detailed Description

BH-30643 is a novel, orally available, non-covalent, macrocyclic, mutant selective OMNI-EGFR inhibitor that targets a broad diversity of mutations in the EGFR kinase domain. These include EGFR classical mutations (e.g., ex19del and L858R) as well as less common (atypical) mutations (including G719X, S768I, L861Q, E709X, and beyond). BH-30643 also overcomes a variety of mutations which can cause resistance to previously approved EGFR TKIs (including both C797S and T790M). BH-30643 was designed to be selective over wildtype EGFR and HER2.

Eligibility Criteria

Age Range: 18 years to No maximum

Inclusion Criteria: * ≥ 18 years or legal adult. * Pathologically confirmed diagnosis of locally advanced or metastatic NSCLC with EGFR (classical, atypical, exon20 insertion) or HER2 mutations in the kinase domain of exons 18, 19, 20, or 21. EGFR mutations include activating and acquired EGFR resistance mutations that might form compound mutations. * Had received standard therapies. * Has at least 1 measurable target extracranial lesion according to RECIST v1.1. * Eastern Cooperative Oncology Group Performance Status ≤ 1. * Has a life expectancy of ≥ 3 months. * Has adequate hematologic, hepatic, and renal function. \*The above are a summary; other Inclusion Criteria details may apply. Exclusion Criteria: * History of any concurrent malignancy within the previous 2 years. * Known other oncogenic driver alterations (eg, moderate or high MET amplification) or histological transformation (eg, to small cell carcinoma, etc.). * Unresolved toxicities from prior therapies. * Any significant and uncontrolled medical condition, such as infection. * History of interstitial lung disease from any cause * Clinically significant cardiovascular event within 6 months or significant history of major organ. * Actively receiving investigational therapy(ies) in another clinical study. \*The above are a summary; other Exclusion Criteria details may apply.

Interventions

DRUG

BH-30643

DRUG

BH-30643

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Conditions

NSCLC (Advanced Non-small Cell Lung Cancer)

Locations

Mayo Clinic Hospital - Arizona

Phoenix, Arizona 85054

United States

The Regents of the University of California - Irvine, CA Campus

Irvine, California 92697

United States

UC San Diego Moores Cancer Center

La Jolla, California 92093

United States

University of California, Davis Comprehensive Cancer Center

Sacramento, California 95817

United States

Stanford University Medical Center

Stanford, California 94305

United States

Yale University - Cancer Center

New Haven, Connecticut 06520

United States

Georgetown University Medical Center

Washington D.C., District of Columbia 20007

United States

Mayo Clinic - Florida

Jacksonville, Florida 32224

United States

Sarah Cancer Research Institution - Florida Cancer Specialist

Orlando, Florida 32827

United States

Moffitt Cancer Center

Tampa, Florida 33612

United States

Northwestern Medicine - Northwestern Memorial Hospital Galter Pavilion

Chicago, Illinois 60611

United States

Massachusetts General Hospital

Boston, Massachusetts 02214

United States

Beth Israel Deaconess Medical Center

Boston, Massachusetts 02215

United States

Dana-Farber Cancer Institute

Boston, Massachusetts 02215

United States

Henry Ford Health

Detroit, Michigan 48202

United States

Mayo Clinic Hospital - Rochester, MN

Rochester, Minnesota 55905

United States

Laura & Isaac Perlmutter Cancer Center at NYU Langone Health

New York, New York 10016

United States

Memorial Sloan Kettering Cancer Center

New York, New York 10065

United States

Duke Cancer Institute

Durham, North Carolina 27710

United States

Thomas Jefferson University, Sidney Kimmel Cancer Center

Philadelphia, Pennsylvania 19107

United States

Sarah Cannon Research Institute, LLC

Nashville, Tennessee 37203

United States

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

Houston, Texas 77030

United States

NEXT Virginia

Fairfax, Virginia 22031

United States

Fred Hutchinson Cancer Center

Seattle, Washington 98109

United States

Austin Health

Heidelberg, Victoria 3084

Australia

Peter MacCallum Cancer Centre

Melbourne, Victoria 3000

Australia

Cross Cancer Insitute

Edmonton, Alberta T6G1Z2

Canada

Princess Margaret Cancer Centre

Toronto, Ontario M5G 2C4

Canada

Prince of Wales Hospital

Shatin, New Territories

Hong Kong

Queen Mary Hospital

Hong Kong,

Hong Kong

National Cancer Center Hospital East

Kashiwa, Chiba 227-8577

Japan

Kindai University Hospital

Osakasayama-shi, Osaka

Japan

National Cancer Center Hospital

Tsukiji, Tokyo

Japan

Sarawak General Hosital

Kuching, Sarawak 93586

Malaysia

National University Hospital

Kent Ridge, 119074

Singapore

National Cancer Centre - Singapore

Singapore, 168583

Singapore

Seoul National University Hospital

Seoul, 03080

South Korea

Asan Medical Center

Seoul, 05505

South Korea

Samsung Medical Center

Seoul, 06351'

South Korea

Taichung Veterans General Hospital

Taichung, 407219

Taiwan

National Taiwan University Cancer Center

Taipei,

Taiwan

National Taiwan University Hospital

Taipei,

Taiwan