Trial: Study to Evaluate Efficacy and Safety o…

Trial Details

Sponsor: ArriVent BioPharma, Inc. (industry)

Phase: 3

Start date: Sept. 22, 2025

Planned enrollment: 480

Trial ID: NCT07185997

More trial details at ClinicalTrials.gov

Show Summary from Sponsor

Investigational Drug AI Analysis

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

Overview

Firmonertinib (also known as furmonertinib, alflutinib; development codes AST‑2818/ASK‑120067) is an oral, irreversible, third‑generation EGFR tyrosine‑kinase inhibitor (EGFR‑TKI). It is approved in China for EGFR‑mutant NSCLC and is being investigated globally, including for EGFR exon 20 insertion (ex20ins)–mutated disease. Key randomized and single‑arm trials have reported activity in treatment‑naïve “classical” EGFR mutations and in T790M‑positive disease; multiple studies are evaluating higher doses (160–240 mg QD) for ex20ins. (cancer.gov)

Mechanism of action

Firmonertinib is a mutant‑selective, covalent EGFR‑TKI that targets sensitizing EGFR mutations and the resistance mutation T790M, with relative sparing of wild‑type EGFR. Preclinical work identified ASK‑120067 (firmonertinib) as an irreversible inhibitor that suppresses EGFR signaling and tumor growth in EGFR‑mutant models; Ack1 activation was described as a potential resistance mechanism and a rationale for combination approaches. (molecular-cancer.biomedcentral.com)

Efficacy

First‑line, classical EGFR mutations (ex19del/L858R): In the randomized, double‑blind phase 3 FURLONG trial (N=358), firmonertinib 80 mg QD significantly prolonged progression‑free survival (PFS) versus gefitinib: median PFS 20.8 vs 11.1 months (HR 0.44, 95% CI 0.34–0.58; p<0.0001). A preplanned CNS subgroup analysis showed superior CNS PFS (20.8 vs 9.8 months; HR 0.40) and higher CNS objective response rate (91% vs 65%) with firmonertinib. (pubmed.ncbi.nlm.nih.gov)
Post‑EGFR‑TKI, T790M‑positive disease: A multicenter, single‑arm phase 2b study of limertinib/ASK‑120067 (synonymous with firmonertinib) in 301 patients reported an objective response rate (ORR) of 68.8% (95% CI 63.2–74.0) and median PFS of 11.0 months (95% CI 9.7–12.4); among those with CNS metastases, ORR was 64.6% and median PFS 9.7 months. (pubmed.ncbi.nlm.nih.gov)
EGFR exon 20 insertions: Early clinical datasets suggest activity, particularly at higher doses. Real‑world and retrospective series reported ORRs of 37–67% and median PFS around 6–10 months with 160–240 mg QD dosing; CNS activity has been observed. Prospective development includes the global, randomized phase 3 FURVENT trial (first line ex20ins; 160 mg or 240 mg QD vs platinum‑pemetrexed), which completed enrollment in Q1 2025, with topline results projected in early 2026. (pubmed.ncbi.nlm.nih.gov)

Safety

In FURLONG (first‑line), grade ≥3 treatment‑related adverse events occurred in 11% with firmonertinib vs 18% with gefitinib; no new safety signals were identified. (pubmed.ncbi.nlm.nih.gov)
In the phase 2b T790M‑positive study (ASK‑120067), treatment‑related AEs occurred in 96% of patients; the most common were diarrhea (81.7%), anemia (32.6%), rash (29.9%), and anorexia (28.2%). Grade ≥3 TRAEs occurred in 34.6% (notably diarrhea 13.0%); discontinuation due to TRAEs was 2%, with no treatment‑related deaths. (pubmed.ncbi.nlm.nih.gov)
Exon 20 insertion cohorts/series generally report manageable toxicity, with low rates of grade ≥3 TRAEs at higher doses (160–240 mg QD) and common events including diarrhea and rash. (pubmed.ncbi.nlm.nih.gov)

TrialFetch AI Analysis

Goal: To compare efficacy and safety of first-line firmonertinib 240 mg once daily versus investigator’s choice of osimertinib 80 mg once daily or afatinib 40 mg once daily in patients with locally advanced or metastatic NSCLC harboring uncommon EGFR P-Loop and αC-helix compressing (PACC) mutations.

Patients: Adults with histologically or cytologically confirmed, locally advanced or metastatic NSCLC not amenable to curative therapy, with documented EGFR PACC mutations in tissue or blood. No prior systemic therapy for advanced disease or prior EGFR-targeted agents is allowed. Prior adjuvant/neoadjuvant therapy is permitted if the treatment-free interval is at least 12 months. Patients with asymptomatic CNS metastases are eligible.

Design: Global, randomized, multicenter, open-label phase 3 study with 1:1 allocation to experimental versus active-comparator EGFR TKI. Planned enrollment is 480 participants.

Treatments: Experimental arm: firmonertinib 240 mg orally once daily. Firmonertinib (also called furmonertinib/alflutinib; AST-2818/ASK-120067) is an oral, third‑generation, mutant‑selective, covalent EGFR TKI targeting sensitizing mutations and T790M with relative sparing of wild-type EGFR. In the phase 3 FURLONG trial in classical EGFR-mutant NSCLC, firmonertinib 80 mg improved PFS versus gefitinib and showed CNS activity; single-arm studies demonstrated responses in T790M-positive disease, and higher doses (160–240 mg) show activity in exon 20 insertions. Active comparator arm: investigator’s choice of osimertinib 80 mg QD or afatinib 40 mg QD, both standard EGFR TKIs used in EGFR-mutant NSCLC.

Outcomes: Primary endpoints: BICR-assessed progression-free survival per RECIST v1.1 and confirmed overall response rate by BICR. Key secondary endpoints include overall survival, investigator-assessed PFS and confirmed ORR, duration of response, time to second progression (PFS2), and safety/tolerability including adverse events and changes in clinical laboratory parameters. Follow-up duration for efficacy and safety endpoints extends up to approximately 3–5 years depending on the measure.

Burden on patient: Overall burden is expected to be low to moderate. Study drugs are oral daily therapies without protocol-mandated infusions. Assessments will likely mirror standard-of-care monitoring for metastatic EGFR-mutant NSCLC, including periodic imaging (typically every 6–12 weeks), routine safety labs, and clinical visits. No intensive pharmacokinetic sampling or mandatory repeat biopsies are described. Participation may require regular travel to study sites for imaging and safety assessments over several years, and patients with CNS metastases may have additional brain imaging at intervals consistent with standard practice.

Last updated: Nov 2025

Eligibility

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Sites (56)

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Blacktown Cancer and Haematology Centre

Blacktown, New South Wales, 2148, Australia

No email / No phone

Status: Recruiting

Chris O'Brien Lifehouse

Camperdown, New South Wales, 2050, Australia

No email / No phone

Status: Recruiting

GenesisCare North Shore Health Hub

St Leonards, New South Wales, 2065, Australia

No email / No phone

Status: Recruiting

Austin Health

Heidelberg, Victoria, 3084, Australia

No email / No phone

Status: Recruiting

Sunnybrook Research Institute

Toronto, Ontario, M4N 3M5, Canada

No email / No phone

Status: Recruiting

The Ottawa Hospital Cancer Centre

Ottawa, Ontario, K1H 8L6, Canada

No email / No phone

Status: Recruiting

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

Thessaloniki, 570 01, Greece

No email / No phone

Status: Recruiting

Henry Dunant Hospital Center

Athens, 115 26, Greece

No email / No phone

Status: Recruiting

Thoracic General Hospital of Athens I Sotiria

Thessaloniki, 570 01, Greece

No email / No phone

Status: Recruiting

Humanity and Health Clinical Trial Centre

Central, Hong Kong

No email / No phone

Status: Recruiting

Queen Mary Hospital

Hong Kong, 000000, Hong Kong

No email / No phone

Status: Recruiting

Istituto Europeo di Oncologia (IEO)

Milan, 20141, Italy

No email / No phone

Status: Recruiting

SOC Oncologia Medica e dei Tumori Immuno-correlati

Aviano, 33081, Italy

No email / No phone

Status: Recruiting

Aichi Cancer Center

Nagoya, Aichi-ken, 464-8681, Japan

No email / No phone

Status: Recruiting

Kurume University Hospital

Kurume-Shi, Fukuoka, 830-0011, Japan

No email / No phone

Status: Recruiting

National Hospital Organization Hokkaido Cancer Center

Sapporo, Hokkaido, 003-0804, Japan

No email / No phone

Status: Recruiting

Hyogo Cancer Center

Akashi-shi, Hyōgo, 673-8558, Japan

No email / No phone

Status: Recruiting

Miyagi Cancer Center

Natori-shi, Miyagi, 981-1293, Japan

No email / No phone

Status: Recruiting

Niigata Cancer Center Hospital

Niigata, Niigata, 951-8566, Japan

No email / No phone

Status: Recruiting

Kansai Medical University Hospital

Hirakata-shi, Osaka, 573-1191, Japan

No email / No phone

Status: Recruiting

National Cancer Center Hospital

Chuo-ku, Tokyo, 104-0045, Japan

No email / No phone

Status: Recruiting

Nippon Medical School Hospital

Bunkyo-ku, Tokyo, 113-8603, Japan

No email / No phone

Status: Recruiting

Tokyo Metropolitan Komagome Hospital

Bunkyō-Ku, Tokyo, 113-8677, Japan

No email / No phone

Status: Recruiting

Hospital Kuala Lumpur

Kuala Lumpur, WP Kuala Lumpur, 50586, Malaysia

No email / No phone

Status: Recruiting

Curie Oncology (Farrer)

Singapore, 217562, Singapore

No email / No phone

Status: Recruiting

National Cancer Centre Singapore

Singapore, 168583, Singapore

No email / No phone

Status: Recruiting

Tan Tok Seng Hospital

Singapore, 308433, Singapore

No email / No phone

Status: Recruiting

Asan Medical Center

Seoul, 05505, South Korea

No email / No phone

Status: Recruiting

Gachon University Gil Medical Center

Incheon, 21565, South Korea

No email / No phone

Status: Recruiting

Kangbuk Samsung Hospital

Seoul, 03181, South Korea

No email / No phone

Status: Recruiting

Samsung Medical Center

Seoul, 06351, South Korea

No email / No phone

Status: Recruiting

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

Suwon, Gyeonggi-do, 16247, South Korea

No email / No phone

Status: Recruiting

Chonnam National University Hwasun Hospital

Hwasun, Jeollanam-do, 58128, South Korea

No email / No phone

Status: Recruiting

Hospital Clinic de Barcelona

Barcelona, 08036, Spain

No email / No phone

Status: Recruiting

Hospital QuironSalud Malaga

Málaga, 29004, Spain

No email / No phone

Status: Recruiting

Hospital Universitario Central de Asturias

Oviedo, 33011, Spain

No email / No phone

Status: Recruiting

Hospital Universitario y Politecnico La Fe

Valencia, 46026, Spain

No email / No phone

Status: Recruiting

Hospital Universitari Son Espases

Palma, Balearic Islands, 07120, Spain

No email / No phone

Status: Recruiting

Kaohsiung Medical University Chung-Ho Memorial Hospital

Kaohsiung City, 807, Taiwan

No email / No phone

Status: Recruiting

Taichung Veterans General Hospital

Taichung, 407219, Taiwan

No email / No phone

Status: Recruiting

The Royal Marsden NHS Foundation Trust

London, SW3 6JJ, United Kingdom

No email / No phone

Status: Recruiting

The Christie NHS Foundation Trust

Manchester, England, M20 4BX, United Kingdom

No email / No phone

Status: Recruiting

University College London Hospitals NHS Foundation Trust

London, England, NW1 2PG, United Kingdom

No email / No phone

Status: Recruiting

Kaiser Permanente Medical Center

Vallejo, California, 94589, United States

No email / No phone

Status: Recruiting

UCSF Medical Center-Mission Bay

San Francisco, California, 94158, United States

No email / No phone

Status: Recruiting

USC/Norris Comprehensive Cancer Center

Los Angeles, California, 90033, United States

No email / No phone

Status: Recruiting

University of California Davis Comprehensive Cancer Center

Sacramento, California, 95817, United States

No email / No phone

Status: Recruiting

Illinois Cancer Specialists

Arlington Heights, Illinois, 60005, United States

No email / No phone

Status: Recruiting

University of Illinois Hospital and Health Sciences Systems

Chicago, Illinois, 60612, United States

No email / No phone

Status: Recruiting

Laura & Isaac Perlmutter Cancer Center at NYU Langone Health

New York, New York, 10016, United States

No email / No phone

Status: Recruiting

Fox Chase Cancer Center

Philadelphia, Pennsylvania, 19111, United States

No email / No phone

Status: Recruiting

Texas Oncology

Dallas, Texas, 75246, United States

No email / No phone

Status: Recruiting

The University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

No email / No phone

Status: Recruiting

Shenandoah Oncology, P.C.

Winchester, Virginia, 22601, United States

No email / No phone

Status: Recruiting

University of Virginia

Charlottesville, Virginia, 22903, United States

No email / No phone

Status: Recruiting

Virginia Cancer Specialists

Fairfax, Virginia, 22031, United States

No email / No phone

Status: Recruiting

Trial Details

Show Summary from Sponsor

Investigational Drug AI Analysis

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

Overview

Mechanism of action

Efficacy

Safety

Further reading

TrialFetch AI Analysis

Eligibility

Show Criteria

Sites (56)

Blacktown Cancer and Haematology Centre

Chris O'Brien Lifehouse

GenesisCare North Shore Health Hub

Austin Health

Sunnybrook Research Institute

The Ottawa Hospital Cancer Centre

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

Henry Dunant Hospital Center

Thoracic General Hospital of Athens I Sotiria

Humanity and Health Clinical Trial Centre

Queen Mary Hospital

Istituto Europeo di Oncologia (IEO)

SOC Oncologia Medica e dei Tumori Immuno-correlati

Aichi Cancer Center

Kurume University Hospital

National Hospital Organization Hokkaido Cancer Center

Hyogo Cancer Center

Miyagi Cancer Center

Niigata Cancer Center Hospital

Kansai Medical University Hospital

National Cancer Center Hospital

Nippon Medical School Hospital

Tokyo Metropolitan Komagome Hospital

Hospital Kuala Lumpur

Curie Oncology (Farrer)

National Cancer Centre Singapore

Tan Tok Seng Hospital

Asan Medical Center

Gachon University Gil Medical Center

Kangbuk Samsung Hospital

Samsung Medical Center

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

Chonnam National University Hwasun Hospital

Hospital Clinic de Barcelona

Hospital QuironSalud Malaga

Hospital Universitario Central de Asturias

Hospital Universitario y Politecnico La Fe

Hospital Universitari Son Espases

Kaohsiung Medical University Chung-Ho Memorial Hospital

Taichung Veterans General Hospital

The Royal Marsden NHS Foundation Trust

The Christie NHS Foundation Trust

University College London Hospitals NHS Foundation Trust

Kaiser Permanente Medical Center

UCSF Medical Center-Mission Bay

USC/Norris Comprehensive Cancer Center

University of California Davis Comprehensive Cancer Center

Illinois Cancer Specialists

University of Illinois Hospital and Health Sciences Systems

Laura & Isaac Perlmutter Cancer Center at NYU Langone Health

Fox Chase Cancer Center

Texas Oncology

The University of Texas MD Anderson Cancer Center

Shenandoah Oncology, P.C.

University of Virginia

Virginia Cancer Specialists