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NCT07185997PHASE3Recruiting

Study to Evaluate Efficacy and Safety of Firmonertinib Compared With Investigator's Choice of EGFR Inhibitor as First-Line Treatment in Participants Who Have Locally Advanced or Metastatic NSCLC With EGFR P-Loop and Alpha C-Helix Compressing (PACC) Uncommon Mutations

ArriVent BioPharma, Inc.

Start Date

12/17/2025

Completion Date

12/1/2030

Summary

Global, Phase 3, randomized, multicenter, open-label study evaluating the efficacy and safety of firmonertinib at a dose level of 240 mg QD compared to investigator's choice of osimertinib (80 mg QD) or afatinib (40 mg QD) in participants who have locally advanced or metastatic NSCLC with EGFR PACC mutations, and who have not received any prior therapy for advanced disease. Participants will be randomized in a 1:1 ratio to treatment with firmonertinib or osimertinib or afatinib and will take the assigned dose daily.

Eligibility Criteria

Age Range: 18 years to No maximum

Key Eligibility Criteria: * Histologically or cytologically documented, locally advanced or metastatic Non-Small Cell Lung Cancer (NSCLC) not amenable to curative surgery or radiotherapy. * Documented results of the presence of an Epidermal Growth Factor Receptor (EGFR) PACC mutation in tumor tissue or blood from local testing. * No prior systemic anticancer therapy regimens received for locally advanced or metastatic Non-Small Cell Lung Cancer (NSCLC) including prior treatment with any Epidermal Growth Factor Receptor (EGFR)-targeting agents (e.g., previous (EGFR) TKIs, monoclonal antibodies, or bispecific antibodies). * Patients who have received prior neo-adjuvant and/or adjuvant chemotherapy, immunotherapy, or chemo radiotherapy for non-metastatic disease must have experienced a treatment free interval of at least 12 months. * Patients with asymptomatic CNS metastases are eligible.

Interventions

DRUG

Firmonertinib

DRUG

EGFR-TKI inhibitor based on investigator's choice

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Conditions

Non-Small-Cell Lung CancerMetastatic Non-Small-Cell Lung CancerAdvanced Non-Small-Cell Lung CancerEGFR P-Loop and Alpha C-Helix CompressingEGFR PACCEGFR Uncommon Mutations

Locations

USC/Norris Comprehensive Cancer Center

Los Angeles, California 90033

United States

University of California Davis Comprehensive Cancer Center

Sacramento, California 95817

United States

UCSF Medical Center-Mission Bay

San Francisco, California 94158

United States

Kaiser Permanente Medical Center

Vallejo, California 94589

United States

University of Colorado Health

Aurora, Colorado 80045

United States

Illinois Cancer Specialists

Arlington Heights, Illinois 60005

United States

University of Illinois Hospital and Health Sciences Systems

Chicago, Illinois 60612

United States

Northwell Health/R.J. Zuckerberg Cancer Center

Lake Success, New York 11042

United States

Laura & Isaac Perlmutter Cancer Center at NYU Langone Health

New York, New York 10016

United States

Ohio State University Hospitals

Columbus, Ohio 43210

United States

Fox Chase Cancer Center

Philadelphia, Pennsylvania 19111

United States

Texas Oncology

Dallas, Texas 75246

United States

The University of Texas MD Anderson Cancer Center

Houston, Texas 77030

United States

University of Virginia

Charlottesville, Virginia 22903

United States

Virginia Cancer Specialists

Fairfax, Virginia 22031

United States

Shenandoah Oncology, P.C.

Winchester, Virginia 22601

United States

Swedish Cancer Institute

Edmonds, Washington 98026

United States

Blacktown Cancer and Haematology Centre

Blacktown, New South Wales 2148

Australia

Chris O'Brien Lifehouse

Camperdown, New South Wales 2050

Australia

GenesisCare North Shore Health Hub

St Leonards, New South Wales 2065

Australia

Austin Health

Heidelberg, Victoria 3084

Australia

Alberta Health Services, Tom Baker Cancer Centre

Calgary, Alberta T2N 4N2

Canada

BC Cancer Vancouver Centre

Vancouver, British Columbia V5Z 4E6

Canada

The Ottawa Hospital Cancer Centre

Ottawa, Ontario K1H 8L6

Canada

Sunnybrook Research Institute

Toronto, Ontario M4N 3M5

Canada

Princess Margaret Cancer Centre - University Health Network

Toronto, Ontario M5G 2M9

Canada

Hospices Civil de Lyon

Bron, Auvergne-Rhône-Alpes 69500

France

Hospital Nord de Marseille

Marseille, Bouches-du-Rhone 13915

France

Centre Francois Baclesse

Caen, Calvados 14076

France

Hopital Larrey

Toulouse, Occitanie 31059

France

Centre Leon-Berard

Lyon, 69373

France

Hopital Nord Guilaume-et-Rene-Laennec CHU de Nantes

Saint-Herblain, 44093

France

Insitut de Canderologie d I'Ouest

Saint-Herblain, 44805

France

Henry Dunant Hospital Center

Athens, 115 26

Greece

University General Hospital Attikon - General Hospital of West Attica H AGIA VARVARA

Athens, 124 62

Greece

Athens Medical Center S.A., European Interbalkan Medical Center

Thessaloniki, 570 01

Greece

Thoracic General Hospital of Athens I Sotiria

Thessaloniki, 570 01

Greece

Queen Mary Hospital

Hong Kong, Hong Kong 000000

Hong Kong

Humanity and Health Clinical Trial Centre

Central,

Hong Kong

SOC Oncologia Medica e dei Tumori Immuno-correlati

Aviano, 33081

Italy

Istituto Europeo di Oncologia (IEO)

Milan, 20141

Italy

Aichi Cancer Center

Nagoya, Aichi-ken 464-8681

Japan

Kurume University Hospital

Kurume-Shi, Fukuoka 830-0011

Japan

National Hospital Organization Hokkaido Cancer Center

Sapporo, Hokkaido 003-0804

Japan

Hyogo Cancer Center

Akashi-shi, Hyōgo 673-8558

Japan

Miyagi Cancer Center

Natori-shi, Miyagi 981-1293

Japan

Niigata Cancer Center Hospital

Niigata, Niigata 951-8566

Japan

Kansai Medical University Hospital

Hirakata-shi, Osaka 573-1191

Japan

Nippon Medical School Hospital

Bunkyo-ku, Tokyo 113-8603

Japan

Tokyo Metropolitan Komagome Hospital

Bunkyō-Ku, Tokyo 113-8677

Japan

National Cancer Center Hospital

Chuo-ku, Tokyo 104-0045

Japan

OncoCar Cancer Centre

Petaling Jaya, Selangor 47810

Malaysia

Hospital Kuala Lumpur

Kuala Lumpur, WP Kuala Lumpur 50586

Malaysia

National Cancer Centre Singapore

Singapore, 168583

Singapore

Curie Oncology (Farrer)

Singapore, 217562

Singapore

Tan Tok Seng Hospital

Singapore, 308433

Singapore

The Catholic University of Korea, St. Vincent's Hospital

Suwon, Gyeonggi-do 16247

South Korea

Chonnam National University Hwasun Hospital

Hwasun, Jeollanam-do 58128

South Korea

Gachon University Gil Medical Center

Incheon, 21565

South Korea

Kyung Hee University Hospital

Seoul, 02447

South Korea

Kangbuk Samsung Hospital

Seoul, 03181

South Korea

Asan Medical Center

Seoul, 05505

South Korea

Samsung Medical Center

Seoul, 06351

South Korea

Hospital Universitari Son Espases

Palma, Balearic Islands 07120

Spain

Hospital Clinic de Barcelona

Barcelona, 08036

Spain

Hospital QuironSalud Malaga

Málaga, 29004

Spain

Hospital Universitario Central de Asturias

Oviedo, 33011

Spain

Hospital Universitario y Politecnico La Fe

Valencia, 46026

Spain

Kaohsiung Medical University Chung-Ho Memorial Hospital

Kaohsiung City, 807

Taiwan

Taichung Veterans General Hospital

Taichung, 407219

Taiwan

National Taiwan University Cancer Center

Taipei, 106

Taiwan

Taipei Veterans General Hospital

Taipei, 11217

Taiwan

Mahidol University - Siriraj Hospital

Bangkoknoi, Bangkok 10700

Thailand

Chulabhorn Hospital

Lak Si, Bangkok 10210

Thailand

Prince of Songkla Hospital

Hat Yai, Changwat Songkhla 90110

Thailand

University College London Hospitals NHS Foundation Trust

London, England NW1 2PG

United Kingdom

The Christie NHS Foundation Trust

Manchester, England M20 4BX

United Kingdom

The Royal Marsden NHS Foundation Trust

London, SW3 6JJ

United Kingdom