Comparing firmonertinib to chemotherapy for advanced lung cancer with specific mutations

A Phase III, Randomized, Multicentre, Open Label Study to Assess the Efficacy and Safety of Firmonertinib Versus Platinum Based Chemotherapy as First-line Treatment for Locally Advanced or Metastatic Non-small Cell Lung Cancer Patients With EGFR PACC Mutation or EGFR l861q Mutation

This study is testing whether a new drug called firmonertinib can work better than standard chemotherapy for people with advanced lung cancer who have specific genetic mutations.

Quick facts

• Phase: PHASE3
• Study type: Interventional
• Enrollment: 300 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Allist Pharmaceuticals, Inc. (industry)
• Drugs / interventions: furmonertinib, chemotherapy, immunotherapy, firmonertinib
• Locations: 2 sites (Beijing, Beijing Municipality and 1 other locations)
• Trial ID: NCT06956001 on ClinicalTrials.gov

What this trial studies

This phase III clinical trial is a randomized, open-label study designed to evaluate the efficacy and safety of firmonertinib mesylate compared to platinum-based chemotherapy in patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) who have not received prior systemic therapy and carry specific EGFR mutations (PaCC or L861Q). Approximately 300 eligible patients will be stratified by mutation type and CNS metastasis and randomly assigned to receive either firmonertinib or a dual-agent chemotherapy regimen. The treatment involves daily oral administration of firmonertinib or intravenous administration of chemotherapy agents such as pemetrexed and cisplatin or carboplatin.

Who should consider this trial

Good fit: Ideal candidates include adults aged 18 and older with untreated advanced or metastatic non-squamous NSCLC and confirmed EGFR PACC or L861Q mutations.

Not a fit: Patients with prior systemic therapy for advanced/metastatic NSCLC or those with squamous cell carcinoma are unlikely to benefit from this study.

Why it matters

Potential benefit: If successful, this trial could provide a more effective first-line treatment option for patients with advanced NSCLC harboring specific EGFR mutations.

How similar studies have performed: Other studies have shown promising results with targeted therapies for EGFR mutations in NSCLC, indicating a potential for success with this approach.

Eligibility criteria

Inclusion Criteria:

1. Voluntarily sign the informed consent form (ICF).
2. Age ≥18 years at the time of ICF signing.
3. At least one measurable lesion per RECIST v1.1, meeting the following:

   * No prior local therapy (e.g., radiotherapy)
   * Not used for biopsy during screening
4. Histologically/cytologically confirmed non-squamous NSCLC, classified as:

   * Locally advanced (Stage IIIB/IIIC, unsuitable for curative surgery and/or definitive chemoradiotherapy)
   * Metastatic (Stage IV) (Based on UICC/AJCC 8th edition TNM staging)
5. Agreement to provide:

   * Recent tumor tissue (from untreated lesions)
   * Blood samples
   * Central lab-confirmed EGFR PACC or L861Q mutation (If tumor tissue is unavailable due to inaccessible lesions, sponsor consultation is required.)
6. No prior systemic therapy for advanced/metastatic NSCLC.

   * Allowed if: Prior (neo)adjuvant/definitive chemoradiotherapy completed ≥12 months before recurrence/progression
7. ECOG performance status 0-1.
8. Life expectancy ≥12 weeks.
9. Adequate bone marrow/organ function within 14 days before treatment (no transfusion/G-CSF within 2 weeks prior).
10. Women of childbearing potential (WOCBP):

    * Abstinence or contraception use
    * No egg donation
11. Non-sterilized males:

    * Abstinence or contraception use
    * No sperm donation
12. CNS metastases allowed if protocol-specified criteria are met.

Exclusion Criteria:

1. Histologically/cytologically confirmed tumor with \>10% neuroendocrine carcinoma, sarcomatoid carcinoma, or squamous cell components.
2. Known ALK-positive, ROS1-positive, RET fusion-positive, NTRK fusion-positive, BRAF V600E mutation, MET exon 14 skipping mutation, or other targetable alterations with approved therapies.
3. Prior treatments including:

   1. Systemic anti-tumor therapy for advanced/metastatic NSCLC (e.g., chemotherapy/targeted/immunotherapy). Neoadjuvant/adjuvant therapy exceptions per Inclusion Criterion #6.
   2. \>30 Gy thoracic radiotherapy within 6 months or non-thoracic radiotherapy within 4 weeks prior to first dose (brain radiotherapy exceptions per Inclusion Criterion #12).
   3. Any prior EGFR-targeted therapy (including investigational EGFR-TKIs, mAbs, bispecific antibodies, etc.).
   4. Strong CYP3A4 inhibitors within 7 days or inducers within 21 days prior to first dose.
   5. Anticancer traditional Chinese medicines within 2 weeks prior to first dose.
   6. Non-specific immunomodulators (e.g., interferon, IL-2, thymosin) within 2 weeks prior to first dose.
   7. Major trauma/surgery within 4 weeks prior to treatment initiation.
4. Clinically significant gastrointestinal abnormalities, including:

   * Moderate/severe atrophic gastritis
   * GI obstruction/perforation
   * Chronic diarrhea/short bowel syndrome
   * Major upper GI surgery (e.g., gastrectomy)
   * Inflammatory bowel disease (Crohn's/ulcerative colitis) or active intestinal inflammation
   * Inability to swallow tablets
5. Uncontrolled systemic diseases.
6. Severe acute/chronic infections.
7. Interstitial lung disease (ILD)/non-infectious pneumonia:

   * History requiring clinical intervention
   * Current presence
   * Suspicious imaging findings unresolved at screening
8. Clinically significant cardiovascular dysfunction (active or history).
9. Tumor invasion of critical adjacent structures (heart/esophagus/SVC etc.) with high bleeding/fistula risk. Exceptions may be considered if investigator assesses minimal risk.
10. Pulmonary comorbidities causing severe impairment, including:

    1. Baseline lung diseases (e.g., pulmonary embolism \[≤3 months\], severe asthma/COPD/restrictive disease)
    2. Autoimmune/connective tissue disorders with pulmonary involvement (e.g., rheumatoid arthritis, sarcoidosis)
11. Residual toxicity \>Grade 1 (per NCI CTCAE v5.0) from prior anticancer therapy (except alopecia/neuropathy).
12. Concurrent malignancies except:

    * Cured localized skin cancers (BCC/SCC), superficial bladder cancer, cervical/breast DCIS, or papillary thyroid cancer
    * Other malignancies cured by radical therapy ≥3 years prior
13. Pregnancy/lactation or planned pregnancy within 6 months post-treatment.
14. Inability to comply with study procedures/follow-up.
15. Known hypersensitivity to furmonertinib or excipients.
16. History of allergic reactions to pemetrexed/cisplatin/carboplatin.
17. Other exclusionary per investigator judgment, including:

    * Alcohol/drug abuse
    * Severe comorbidities (including psychiatric) requiring treatment
    * Critical laboratory abnormalities
    * Social/familial factors compromising safety/data collection

Where this trial is running

Beijing, Beijing Municipality and 1 other locations

• Ethics Committee of cancer hospital, Chinese Academy of Medical Sciences — Beijing, Beijing Municipality, China (RECRUITING)
• Shandong Tumor Hospital — Shandong, Jinan, China (RECRUITING)

Study contacts

• Study coordinator: Shanghai Allist Pharmaceuticals Co., Ltd Shanghai Allist Pharmaceuticals Co., Ltd

Conditions: EGFR, NSCLC, firmonertinib