A Global, Phase 3, Randomized, Multicenter, Open-Label Study to Evaluate the Efficacy and Safety of Firmonertinib Compared With Investigator's Choice of Osimertinib or Afatinib as First-Line Treatment in Participants Who Have Locally Advanced or Metastatic Non-Small-Cell Lung Cancer With Epidermal Growth Factor Receptor P-Loop and Alpha C-Helix Compressing (PACC) Uncommon Mutations (ALPACCA)

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Investigational drug late phase More information Active drug More information Low burden on patient More information

Trial Details

Sponsor: ArriVent BioPharma, Inc. (industry)

Phase: 3

Start date: Sept. 22, 2025

Planned enrollment: 480

Trial ID: NCT07185997
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More trial details at ClinicalTrials.gov More info

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Investigational Drug AI Analysis

chevron Show for: Firmonertinib (AST-2818, ASK-120067)

TrialFetch AI Analysis

Goal: Determine whether first-line firmonertinib improves outcomes compared with investigator-selected osimertinib or afatinib in advanced NSCLC with uncommon EGFR PACC mutations.

Patients: Participants have locally advanced or metastatic NSCLC with a documented EGFR PACC mutation and have received no systemic therapy for advanced disease. Asymptomatic CNS metastases are permitted. Prior perioperative treatment is allowed if the treatment-free interval is at least 12 months.

Design: Global, multicenter, open-label trial with 1:1 randomization to firmonertinib or the investigator’s choice of comparator.

Treatments: Participants take oral firmonertinib 240 mg once daily or oral osimertinib 80 mg once daily or afatinib 40 mg once daily. Firmonertinib is an irreversible EGFR tyrosine kinase inhibitor intended to block mutant EGFR signaling. Earlier studies reported a 68.2% confirmed response rate in a small PACC-mutation cohort and longer progression-free survival than gefitinib in patients with common EGFR mutations; neither result establishes benefit over the comparators in this trial. Osimertinib and afatinib are EGFR tyrosine kinase inhibitors used as active comparators.

Outcomes: The primary endpoints are blinded independent central review–assessed progression-free survival by RECIST v1.1 and confirmed overall response rate. Secondary endpoints include overall survival, investigator-assessed progression-free survival and response rate, duration of response, time to second progression, adverse events, and changes in safety laboratory results.

Burden on patient: Expected burden is moderate: treatment is oral and once daily, but participants will need repeated visits for tumor assessments, safety laboratory tests, and adverse-event monitoring, potentially over several years. The provided information does not specify visit or scan frequency or require research biopsies or intensive pharmacokinetic sampling.

Last updated: Sep 2026

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Blacktown Cancer and Haematology Centre

Blacktown, New South Wales, 2148, Australia

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Status: Recruiting

Chris O'Brien Lifehouse

Camperdown, New South Wales, 2050, Australia

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GenesisCare North Shore Health Hub

St Leonards, New South Wales, 2065, Australia

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Austin Health

Heidelberg, Victoria, 3084, Australia

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Sunnybrook Research Institute

Toronto, Ontario, M4N 3M5, Canada

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The Ottawa Hospital Cancer Centre

Ottawa, Ontario, K1H 8L6, Canada

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

Thessaloniki, 570 01, Greece

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Henry Dunant Hospital Center

Athens, 115 26, Greece

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Thoracic General Hospital of Athens I Sotiria

Thessaloniki, 570 01, Greece

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Humanity and Health Clinical Trial Centre

Central, Hong Kong

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Queen Mary Hospital

Hong Kong, 000000, Hong Kong

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Istituto Europeo di Oncologia (IEO)

Milan, 20141, Italy

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SOC Oncologia Medica e dei Tumori Immuno-correlati

Aviano, 33081, Italy

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Aichi Cancer Center

Nagoya, Aichi-ken, 464-8681, Japan

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Kurume University Hospital

Kurume-Shi, Fukuoka, 830-0011, Japan

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National Hospital Organization Hokkaido Cancer Center

Sapporo, Hokkaido, 003-0804, Japan

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Hyogo Cancer Center

Akashi-shi, Hyōgo, 673-8558, Japan

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Miyagi Cancer Center

Natori-shi, Miyagi, 981-1293, Japan

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Niigata Cancer Center Hospital

Niigata, Niigata, 951-8566, Japan

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Kansai Medical University Hospital

Hirakata-shi, Osaka, 573-1191, Japan

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National Cancer Center Hospital

Chuo-ku, Tokyo, 104-0045, Japan

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Nippon Medical School Hospital

Bunkyo-ku, Tokyo, 113-8603, Japan

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Tokyo Metropolitan Komagome Hospital

Bunkyō-Ku, Tokyo, 113-8677, Japan

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Hospital Kuala Lumpur

Kuala Lumpur, WP Kuala Lumpur, 50586, Malaysia

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Curie Oncology (Farrer)

Singapore, 217562, Singapore

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National Cancer Centre Singapore

Singapore, 168583, Singapore

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Tan Tok Seng Hospital

Singapore, 308433, Singapore

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Asan Medical Center

Seoul, 05505, South Korea

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Gachon University Gil Medical Center

Incheon, 21565, South Korea

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Kangbuk Samsung Hospital

Seoul, 03181, South Korea

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Samsung Medical Center

Seoul, 06351, South Korea

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

Suwon, Gyeonggi-do, 16247, South Korea

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Chonnam National University Hwasun Hospital

Hwasun, Jeollanam-do, 58128, South Korea

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Hospital Clinic de Barcelona

Barcelona, 08036, Spain

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Hospital QuironSalud Malaga

Málaga, 29004, Spain

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Hospital Universitario Central de Asturias

Oviedo, 33011, Spain

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Hospital Universitario y Politecnico La Fe

Valencia, 46026, Spain

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Hospital Universitari Son Espases

Palma, Balearic Islands, 07120, Spain

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Kaohsiung Medical University Chung-Ho Memorial Hospital

Kaohsiung City, 807, Taiwan

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Taichung Veterans General Hospital

Taichung, 407219, Taiwan

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The Royal Marsden NHS Foundation Trust

London, SW3 6JJ, United Kingdom

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The Christie NHS Foundation Trust

Manchester, England, M20 4BX, United Kingdom

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University College London Hospitals NHS Foundation Trust

London, England, NW1 2PG, United Kingdom

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Kaiser Permanente Medical Center

Vallejo, California, 94589, United States

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UCSF Medical Center-Mission Bay

San Francisco, California, 94158, United States

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USC/Norris Comprehensive Cancer Center

Los Angeles, California, 90033, United States

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University of California Davis Comprehensive Cancer Center

Sacramento, California, 95817, United States

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Illinois Cancer Specialists

Arlington Heights, Illinois, 60005, United States

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University of Illinois Hospital and Health Sciences Systems

Chicago, Illinois, 60612, United States

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Laura & Isaac Perlmutter Cancer Center at NYU Langone Health

New York, New York, 10016, United States

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Fox Chase Cancer Center

Philadelphia, Pennsylvania, 19111, United States

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Texas Oncology

Dallas, Texas, 75246, United States

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The University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

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Shenandoah Oncology, P.C.

Winchester, Virginia, 22601, United States

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University of Virginia

Charlottesville, Virginia, 22903, United States

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Virginia Cancer Specialists

Fairfax, Virginia, 22031, United States

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