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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

RecruitingPhase 3

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)

Who can join

Ages 18 and older · All sexes

Full eligibility criteria
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.

About the study

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.

What is being tested

Sponsor: ArriVent BioPharma, Inc. · Participants: 480 · Started: Dec 17, 2025

Contact the study team

Official record on ClinicalTrials.gov — NCT07185997

Locations in the U.S.

CaliforniaSt. Jude Medical Center, Fullerton
USC/Norris Comprehensive Cancer Center, Los Angeles
Providence St. Joseph Hospital, Orange
University of California Davis Comprehensive Cancer Center, Sacramento
UCSF Medical Center-Mission Bay, San Francisco
Kaiser Permanente Medical Center, Vallejo
ColoradoUniversity of Colorado Health, Aurora
IllinoisIllinois Cancer Specialists, Arlington Heights
University of Illinois Hospital and Health Sciences Systems, Chicago
MichiganHenry Ford Cancer Institute, Detroit
New YorkNorthwell Health/R.J. Zuckerberg Cancer Center, Lake Success
Laura & Isaac Perlmutter Cancer Center at NYU Langone Health, New York
OhioOhio State University Hospitals, Columbus
PennsylvaniaFox Chase Cancer Center, Philadelphia
TexasTexas Oncology, Dallas
The University of Texas MD Anderson Cancer Center, Houston
VirginiaUniversity of Virginia, Charlottesville
Virginia Cancer Specialists, Fairfax
Shenandoah Oncology, P.C., Winchester
WashingtonSwedish Cancer Institute, Edmonds

Conditions

From ClinicalTrials.gov, data retrieved Sep 29, 2026. Each study sets its own eligibility; the study team decides who can join.