/NCT07185997

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

Trial number:: NCT07185997

Trial phase:: 3

Study type:: Biomarker, Targeted therapy

Overall status:: Recruiting

Study start date

December, 2025

Scientific title

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)

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.

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.

Study design

Primary purpose: TREATMENT, Allocation: RANDOMIZED, Intervention model: PARALLEL, Masking: NONE,

Conditions

Non-Small-Cell Lung Cancer, Metastatic Non-Small-Cell Lung Cancer, Advanced Non-Small-Cell Lung Cancer, EGFR P-Loop and Alpha C-Helix Compressing, EGFR PACC, EGFR Uncommon Mutations

Other study ID numbers

FURMO-006

Choose trial site (63)

Tan Tock Seng Hospital

Curie Oncology (Novena) – #08-29/30 Mount Elizabeth Novena Specialist Centre

1 Farrer Park Station Rd, #10-06/07 Farrer Park Medical Centre, Singapore 217562